February 12th 2016 No 3789 scripintelligence.com

It Was Shkreli’s Show, But Pharma Was On Trial The House Oversight and Government Reform Committee hearing on drug prices was the hottest spot in a very damp and cold Washington on Feb. 4 and former Turing Pharmaceutical Inc. CEO Martin Shkreli gave lawmakers and the overflow-crowd in attendance what they were anticipating: Several big smirky smiles, a lot of eye rolling and a refusal to testify – citing his “Act of Production Privilege” under the Fifth Amendment to the US Constitution at the Fer Gregory/shutterstock.com advice of his counsel. And lawmakers were irked, with the panel’s ranking member, Rep. Elijah Cummings (D-MD), rebuking Shkreli for sneering during the congressman’s opening remarks about STAR OF THE SHOW: Shkreli how Turing had jacked up the price of grilled under intense limelight its recently acquired toxoplasmosis drug Daraprim by more than 5,000%, putting it out of reach of some patients. the witness already had been dismissed, heated confrontations – I have never seen “It’s not funny Mr. Shkreli. People are departing about 45 minutes into the nearly an individual act with such arrogance as dying, and they’re getting sicker and sicker,” four-hour hearing. Mr. Shkreli a while ago, such childish, smart- Cummings scolded. “In all my time in Congress – I’ve served alecky smirks, even turning away from ranking Rep. John Duncan Jr. (R-TN) also had some on four committees, been here 28 years, I’ve member Cummings to pose for pictures while tough words for Shkreli – although by then, seen hundreds of witnesses and some very Turn to page 6 Pfizer’s Currency, Patent Pressures Boost Allergan Pfizer Inc.’s pending $160bn merger with New drugs and current best-sellers will Allergan deal has the potential to boost Allergan PLC may be its best shot at significant contribute to sales growth in 2016, as they this year’s revenue by more than the 0% revenue growth this year, since the company’s did last year, but Pfizer expects to take a to 4% growth rate that is envisioned in the 2015 revenue and earnings fell below 2014 $2.3bn hit from unfavorable foreign currency company’s 2016 financial forecast. totals due to foreign currency impacts and the exchange rates and experience $2.3bn in “The [Allergan] transaction’s about loss of patent exclusivity for multiple products sales losses due to generic competition for accelerating growth potential in our innovative – factors that again could lead to flat growth its branded drugs. Since the $17bn Hospira businesses, and strengthening our established during the current year, despite meaningful Inc. acquisition helped Pfizer keep its 2015 business, and more efficiently allocating our sales gains for certain products. revenue decline to 2%, the much larger Turn to page 10

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Eleanor Malone, Editor, 8 Scrip Intelligence

Are you a man? Do you think that women 1 It Was Shkreli’s Show, 11 Novo Nordisk Says Global Payer But Pharma Was On Trial Pressure Limits Price Rises should get more visibility, more recognition, more power and more money? Do you feel 1 Pfizer’s Currency, 12 Business Bulletin you are in a position to help? Patent Pressures Boost Allergan 13 AstraZeneca Under Pressure But If the answer is yes, take care. 3 Shkreli’s Price-Hike Brag: $45bn Target ‘Still Achievable’ I’m sure you wouldn’t be silly enough to organize a party at a major investment ‘$1bn Here We Come’ Mersana/Takeda Deal Adds To 14 conference to facilitate male appreciation ADC Pipeline 4 Humira Competition Dominates of female models. But even trying to big up AbbVie Earnings 15 Pierre Fabre To Feed R&D Pipeline women by focusing on their brains or their 4 Sanofi Puts Itself Forward 16 Zika Gets Political business acumen isn’t straightforward. For Zika Vaccine Collaboration Only a couple of years ago Scrip editors 17 R&D Bites were consulted on a planned all-female panel Will Liability, Advertising Lawsuits 5 18 NewLink Brings Flavivirus at an industry conference. The male organizer Plague Biosimilars Market? ‘Dream Team’ To Zika wanted to know if it would be “fun” or “repulsive” to subtitle the panel “Biotech Babes.” 5 Medicxi Launches With €210M Fund 18 Witty’s Wish: Hold Off On GSK Break-Up Chatter The topic wasn’t even about being a babe. 7 Policy & Regulation Briefs A tip: if your panel is not about being a 8 FDA ‘Moon Shot’ Center 20 Expert View: French Industry Head woman, don’t make a thing of your panellists To Expedite Combo Cancer Drugs Lauds New Drug Pricing Deal being women. For more on this concept, read journalist Ann Finkbeiner’s 2013 blog Woodcock: Biosimilars Program 21 Stockwatch: Courage Under Fire 9 on publishing a profile of an astronomer Will Explode 22 Pipeline Watch without writing about her “as a woman.” 9 Can ‘Moon Shot’ Lift FDA 23 Appointments This prompted her colleague Christie Out Of Its Silos? Aschwanden to devise The Finkbeiner Test for stories about women in science (along the 11 Alexion Rare Disease Launches Off To Slow Start lines of the Bechdel test, which was created to measure gender bias in film). Another tip: make sure you’re a credible champion. Pharmaguy illustrates his list of Scrip “digitally savvy women pharma pioneers” with an outpouring of colourful hearts Editor: [email protected] Managing Editor: [email protected] erupting from his headshot to garland those News Editor: [email protected] of his female line-up. He wants to bring these South Asia Editor: [email protected] women “into the forefront” – but does this Washington Editor: [email protected] US West Coast Editor: [email protected] forefront have to be decorated in such a Features Editor: [email protected] patronising way? It doesn’t help that he used Senior Reporter: [email protected] a shot of women in bikinis to accompany his Principal Analysts: [email protected]; piece on 2015 drug approvals. [email protected]; [email protected] We would love to hear your comments about Reporter: [email protected] Scrip’s coverage. Feel free to tweet us or post A third tip: be alive to the possible [email protected] Reporter: a discussion on our LinkedIn group, for your irony of your feminist activism. As a man Creative Content Reporter: [email protected] chance to interact with editor Editorial Assistant: [email protected] Eleanor Malone and chair of GlaxoSmithKline – with its Production: [email protected] and the rest of the Scrip Intelligence team. predominantly male leadership team – Sir Pharma Data Editor: [email protected] Philip Hampton could conceivably feel Global Content Director: [email protected] Follow us at: @scripnews a tiny bit awkward about leading a UK All stock images in this publication courtesy of www.shutterstock.com unless otherwise stated. Join us at: linkd.in/scripintelligence government-commissioned review into Customer Services female representation in the management Tel: +44 (0)20 7017 5540 or (US) Toll Free: 1 800 997 3892 and boards of FTSE350 companies. Email: [email protected] As a woman, I feel a tiny bit irritated that, To subscribe, visit scripintelligence.com To advertise, contact [email protected] ironically, a man is in charge of putting Scrip is published by Informa UK Limited. women in charge. ©Informa UK Ltd 2016: All rights reserved. ISSN 0143 7690.

2 February 12th 2016 @scripnews scripintelligence.com © Informa UK Ltd 2016 headline news Shkreli’s Price-Hike Brag: ‘$1bn Here We Come’ Excerpts from more than 300,000 documents, In various emails, Shkreli said he expected including emails, from Turing Pharmaceuticals to make $200m in sales and later declaring Inc. and Valeant Pharmaceuticals International that at the new price of $75,000 per bottle, Inc. painted a picture that’s anything but Turing could rake in $375m for 5,000 bottles pretty about how those firms went about “almost all of it is profit,” adding that he buying older drugs and jacking up their prices believed the firm could pull that in for at least – with the now-former head of one of those three years or more.

companies, Martin Shkreli, declaring “$1bn beeboys/shutterstock.com “Should be a very handsome investment here we come.” for all of us. Let’s all cross our fingers that the Rep. Elijah Cummings (D-MD), the ranking estimates are accurate,” Shkreli said in an email. member on the House Oversight and In his memo about Turing, Cummings said Government Reform Committee, asserted the the documents obtained by the committee documents, which were not made public in indicated the firm’s executives anticipated a their entirety, were proof the tactics used by potential backlash in response to Daraprim’s Turing and Valeant are “not limited to a few price increase, but believed that physicians ‘bad apples,’ but are prominent throughout funds, MSMB Capital Management and MSMB generally were not sensitive to price increases the industry.” Healthcare, and misappropriating more than and that HIV/AIDS advocates could be The two companies have for months been $11m in assets from another of his former managed, despite being vocal. in Cummings’ and other lawmakers’ bulls-eye firms, Retrophin Inc., in what prosecutors One email showed an outside consultant after Turing boosted the price of Daraprim called a Ponzi-like scheme. urged Turing to frame the issue within the (pyrimethamine) by more than 5,000% But a federal judge gave her OK for Shkreli HIV/AIDS community as a “fight between a and Valeant hiked the costs of Nitropress to travel to Washington to comply with the drug company and insurance companies,” (sodium nitroprusside) by 312% and Isuprel Oversight Committee’s subpoena. declaring “There is no love lost between HIV/ (isoprenaline) by 820%. AIDS activists and insurance companies, and Neither Turing nor Valeant developed those they certainly don’t want to be manipulated products. The firms, however, both said they Shkreli thought hiking up by them to fight on their behalf.” now offer discounts to hospitals on their Daraprim’s price would boost Cummings also pointed to emails showing prices. Turing executives were aware patients were Cummings and his staff put only some drug’s sales to several hundred having difficulty affording their insurance details of what they found in the thousands co-pays for Daraprim – one as high as $16,830 of pages of Turing and Valeant documents million dollars – and that hospitals were having to resort into two memos sent to members on the to other, less effective medicines because Oversight Committee. The hearing, however, was postponed from the high price of the company’s drug was But the Maryland lawmaker, nonetheless, Jan. 26 to Feb. 4 because of the “Snowzilla” breaking their pharmacy budgets. argued the documents were evidence the storm, which blanketed Washington in about The lawmaker said the documents also companies purchased the drugs with the two feet of snow just a few days before. showed that instead of lowering its price purpose of dramatically raising their prices, Besides Shkreli, others slated to testify include on Daraprim to previous level in response with the intent of pocketing “millions of Turing’s chief commercial officer Nancy Retzlaff; to widespread concerns by hospitals and dollars” by exploiting the existing monopolies Janet Woodcock, director of the FDA’s Center patients, Turing employed a public relations on the medicines, for which there currently for Drug Evaluation and Research; Mark Merritt, strategy to try to divert attention to patient are no generic competitors. president and CEO of the pharmaceutical assistance programs and research and The memos were sent to the committee care management association, a trade group development efforts, while company officials members two days before the panel holds representing pharmacy benefit managers; and joked in their internal communication about a hearing on drug prices – an event Shkreli Howard Schiller, who early last month stepped their strategy and the fact they had no plans is under subpoena to attend, although his in to substitute in the interim as CEO at Valeant to really lower Daraprim’s price. now-former attorneys, who were replaced for an ailing Michael Pearson, who said on Jan. Cummings said documents from Valeant by high-profile New York criminal defense 25 he was “on the road to recovery,” although showed it used the very same strategy to lawyer Benjamin Brafman, late last month told the timeline for his return remains “uncertain.” divert attention on its prices. Cummings and the head of the committee, Cummings said a review of the Turing He said Valeant also used the patient Jason Chaffetz (R-UT), their client planned to documents showed that Shkreli thought that assistant programs to justify raising prices and assert his “Act of Production Privilege” under by hiking up Daraprim’s price, he could boost to generate increased revenues by driving the Fifth Amendment to the US Constitution the drug’s sales from $10m per year to several patients into closed distribution systems. and would refuse to testify. hundred million dollars. Valeant and Turing are both being probed Shkreli’s lawyers initially said he could not Shkreli’s “$1bn here we come” remark by state and federal investigators about their appear on Capitol Hill in person because came in a May 27, 2015 email to Turing’s pricing and other business practices. his travel was restricted to the southern and chair in response to the news the firm The companies also are the subject eastern districts of New York as a condition of was close to sealing its deal on acquiring of an investigation by the Senate Aging his $5m bond posted for his release from jail Daraprim from Impax Laboratories, which Committee, which intends to eventually call after he was arrested and charged on Dec. 17 ended up selling the drug for $55m to the Turing and Valeant to testify as part of a series with defrauding investors in his former hedge company this past August. of hearings. [email protected]

© Informa UK Ltd 2016 @scripnews scripintelligence.com February 12th 2016 3 headline news Humira Competition Dominates AbbVie Earnings AbbVie CEO Rick Gonzalez disappointed “Obviously as the brand gets a little bit already submitted an application to FDA for analysts by talking little about the company’s bigger, the growth rate as a percentage is approval of a biosimilar Humira. hepatitis C strategy on its year-end slowing down a bit. And then we have built Gonzalez added, conversely, that he conference call, but the specialty pharma in what are a set of assumptions of what kind expects Humira to hit its peak sales leader made some striking comments about of price impact we might see from Enbrel in internationally in 2018 after both indirect its best-selling drug Humira and potential certain markets, particularly in Europe, and and direct competition from biosimilars competition from biosimilars. that represents about 2% of our growth,” enter that market. The blockbuster rheumatoid arthritis noted Gonzalez. When asked about price increases for the drug continued to impress, bringing in 2015 While biosimilar competition is becoming top-selling drug, the CEO added that only revenues of $14bn, up 11.7% from the year- more of a reality every day and the company 25% of Humira growth came from price prior. The drug made up more than half of is conceding that it will have a small impact increases, amounting to about 2% of the AbbVie’s $22.8bn in total sales for the year internationally, Gonzalez still believes that the company’s overall growth. “But overall the vast – so, not shockingly, anything that could large molecule copycats are not a significant majority of our growth whether it be HUMIRA threaten Humira (adalimumab) sales are of threat to the blockbuster franchise in the or other assets in our pipeline is driven by interest to analysts and investors. near-term. volume growth,” he said. “Humira has averaged well over $1bn The executive told analysts during the Analysts had been hoping that the of annual growth for a number of years. In conference call that many of them had made company would talk about its strategy in 2016, we expect Humira to once again be an inaccurate assumptions in their models for hepatitis C now that Merck & Co. has gotten important contributor to our performance AbbVie, specifically related to Humira sales approval from FDA for its latest HVC offering with high-teens growth expected in the US,” through 2020. that will put pressure on AbbVie’s Viekira Pak. said chief financial officer Bill Chase during “What I would say is the biggest difference Gonzalez only addressed the the Jan. 29 conference call. “Internationally, we between consensus and our forecast is competition briefly, saying, “As far as HCV are forecasting mid-single-digit operational that some people are still forecasting that is concerned, as we planned out for 2016, growth, reflecting the latest market dynamics Humira sees biosimilar competition in the I’d say the Merck label came in pretty including the launch of a biosimilar for Enbrel.” United States… probably now in that 2019 much spot on what we had expected. So I While AbbVie and Gonzalez have timeframe,” said the CEO, who assumes the think it’s within our expectations. We have downplayed the threat of biosimilars to product will be able to stave off US biosimilar built into our assumptions for HCV a level Humira in the past, the company conceded competition until 2020, even 2022. of competition and some level of price on its 2015 year-end call that that there will AbbVie currently has patents that cover the competition. We’re going to have to see be “indirect competition” now that a biosimilar drug in the US until 2022, but those patents how that plays out.” of Enbrel is entering the European market. are being challenged by Amgen, which has [email protected] Sanofi Puts Itself Forward For Zika Vaccine Collaboration Update – Sanofi Pasteur has officially to infect 3-4 million people in the next 12 and similar European regulatory bodies, launched a vaccine R&D project targeting months across the Americas. Sanofi already will be essential for accelerated discovery, the prevention of Zika virus (ZIKV) infection has an approved vaccine for Dengue virus, development and approval of any viable and disease. which is spread by the same mosquitos vaccine candidates. Recently Sanofi Pasteur confirmed it was as ZIKV and Yellow virus, so the firm’s Scientists at the US National Institute of reviewing its technologies in order to help expertise has been called upon to assist with Allergy and Infectious Diseases (NIAID), part develop a potential vaccine – however treatment development. of the NIH, last week said they are working on the vaccine specialist said there are many Sanofi said: “We will leverage our extensive two potential vaccine candidates. NIAID said it “unknowns” about this new virus. Now experience, both from a scientific and will be relying on biopharmaceutical partners the company has initiated R&D for a ZIKV- industrial technology perspective with the to help move the candidates through clinical specific vaccine. dengue vaccine, to accelerate discovery of a development. Cases of ZIKV, a disease transmitted viable vaccine candidate for Zika.” Small biotech Inovio Pharmaceuticals has by the Aedes Aegypti mosquito, have The big pharma added that during a DNA-based vaccine candidate in preclinical amplified in the Americas since May 2015 development of its dengue vaccine the studies in collaboration with GeneOne Life and the virus has been linked with a company established “strong working Science; and GlaxoSmithKline plc has also large increase of neurological defects in relationships with the scientific, public health recently said it will review its capabilities for newborns in Brazil. Since October 2015 policy and regulatory communities in Brazil,” possible R&D of a ZIKV vaccine. around 4,000 babies have been born in and in other countries where dengue is The most common symptoms of ZIKV the country with microcephaly, which endemic. “These relationships and clinical and disease are fever, rash, joint pain and causes abnormally small heads and possible regulatory science insights could be valuable conjunctivitis (red eyes). The link between ZIKV brain damage. to the potential clinical development of a and microcephaly is still being researched There currently are no vaccines or ZIKV vaccine candidate,” Sanofi said. and has not yet been clinically confirmed. therapeutics available to prevent or treat Sanofi said strong collaboration between However, no other cause for the sharp rise in ZIKV and last week the World Health pharma, the Brazilian Ministry of Health, the condition in Brazil has been suggested. Organization (WHO) said it expects ZIKV the US National Institutes of Health (NIH) [email protected]

4 February 12th 2016 @scripnews scripintelligence.com © Informa UK Ltd 2016 headline news

Will Liability, Advertising Lawsuits Medicxi Launches Plague Biosimilars Market? With €210M Fund While generic drug makers are shielded Court’s rulings in Pliva v. Mensing and Mutual Index Ventures has spun off its life against failure-to-warn and design-defect Pharmaceutical v. Bartlett. sciences team, portfolio companies and lawsuits thanks to some rulings in recent In Mensing, the high court ruled 5-4 in funds into a new venture capital firm years by the US Supreme Court – although June 2011 that generic drug makers do not called Medicxi Ventures, a validation of that could change if an FDA proposal on have the same obligations as brand-name its ‘asset-centric’ approach to investing. updating labeling with safety information for manufacturers to update product labeling The new firm launches with the close of those products goes into effect – that may when new risks come to light. Medicxi Ventures 1 (MV1), a new €210m not be the case for companies that make and In Mutual, the Supreme Court, also in a 5-4 ($250m) fund that will continue focusing market biosimilars, said Elaine Herrmann Blais, ruling in June 2013, said state law design- on asset-centric, early-stage investments a partner and head of litigation at Goodwin defect claims that turn on the adequacy of a in European life science programs. Procter’s Boston office. drug’s warnings are preempted by federal law Medicxi Ventures will be managed Indeed, where generics’ active under the Mensing decision. by four general partners: Francesco De ingredients are supposed to be identical, The FDA, however, proposed a rule in Rubertis, David Grainger, Kevin Johnson and or bioequivalent, to brand-name drugs and November 2013 that would permit generic Michèle Ollier. The four previously led the the same in dosage form, safety, strength, drug makers to independently revise their life sciences practice of Index Ventures. Read route of administration, quality, performance product labeling to add new safety updates an in-depth interview with De Rubertis and characteristics and intended use, there is before regulators review or approve such Johnson about Medicxi Ventures online at: no statute or regulation requiring that for changes – just like brand-name manufacturers http://bit.ly/1Te5l3R. biosimilars, which must only show they already do. Medicxi’s inaugural fund MV1 includes are “highly similar” to the FDA-approved The agency, which held a public meeting GlaxoSmithKline and Johnson & Johnson; innovator medicine and have no “clinically on the matter last year, initially said it would both companies were investors in MV1’s meaningful” differences in safety and finalize that rule by December 2014, but predecessor fund Index Life 6 (IL6). As in effectiveness from the reference product, delayed that decision until this summer. IL-6, the two pharma companies will not Blais explained. PhRMA and the Generics Pharmaceutical receive any specific rights to the portfolio So while the law is fairly clear that most Association, which often disagree on many companies. failure-to-warn and design-defect product matters, joined together in fighting the The number of exits over the last couple liability claims against generic manufacturers proposed generics labeling rule – arguing of years, “particularly XO1 to J&J,” gave are pre-empted, there are questions about it would result in safety information Medicxi the confidence to strike out on its, how the courts will act in such lawsuits varying among drugs with the same active De Rubertis told Scrip. Success was in large brought against biosimilars makers, Blais said. ingredients, thereby ultimately confusing part due to the “added value” received from She noted the FDA has yet to act on its doctors and patients. the participation of pharma companies, “in labeling guidance for biosimilars, “so we don’t It remains to be seen, however, whether the terms of brainstorming ideas and designing know how similar they’ll be” to the innovators FDA will impose a similar rule for biosimilars. experiments” that are relevant to pharma. product’s label. But in the meantime, Blais said, there “We believe in the potential to create “We don’t know yet how much of the is no FDA requirement for “sameness” for an exciting pipeline of new medicine branded label the FDA will require the biosimilars, so the pre-emption doctrine candidates by collaborating and investing biosimilar to use, which ultimately could may not bar plaintiffs from bringing failure- with an asset-centric model,” commented impact whether such products are shielded to-warn claims in state courts against Dr Moncef Slaoui, GSK’s representative on like generic drugs, Blais said. manufacturers of those products for failing Medicxi’s scientific advisory board. In a joint citizen petition to the FDA, the to include adequate safety warnings, even Dr Richard Mason, head of Johnson & Pharmaceutical Research and Manufacturers if the labeling is the same as the innovator Johnson Innovation, London, added: “We of America (PhRMA) and the Biotechnology medicines. are optimistic that applying the asset-centric In addition, she said, because biosimilars Innovation Organization have called for the investment model of Medicxi across Europe agency to require the labeling for biosimilars have a different structure than the branded and beyond will uncover the new and to clearly state they are indeed, biosimilars, product, it could be argued that the highly differentiated science and technology and should include a description of the biosimilars are not protected from design- that is needed to turn early stage research nonclinical and clinical data supporting defect claims by the Supreme Court’s ruling. into viable products and patient solutions.” the product’s approval, a narrative of the Blais said biosimilars companies also “The creation of Medicxi Ventures as basis for licensure of each indication and a have another problem to contend with a new entity is a natural evolution given statement about whether the agency made a that doesn’t affect generic makers – the that Index’ life sciences team has been determination of interchangeability with the risks of being accused of making false operating autonomously within the referenced innovator medicine, including a claims or misleading statements in product firm for several years,” said Neil Rimer, result of that finding. AbbVie Inc. submitted a advertising. co-founder of Index Ventures. “Whilst Index similar petition to the FDA. Unlike generics, biosimilars will not and Medicxi will operate independently, “The law is pretty clear that most failure- automatically be substituted at the pharmacy, we retain close ties and look forward to to-warn and design-defect product liability so manufacturers of those products must continuing to share ideas and expertise.” claims against generic manufacturers are pre- advertise to compete with the innovators. [email protected] empted,” Blais said, pointing to the Supreme [email protected]

© Informa UK Ltd 2016 @scripnews scripintelligence.com February 12th 2016 5 headline news

It Was Shkreli’s Show, But Pharma Was On Trial (Continued from page 1) the ranking member was speaking. And I think in tow by a large gaggle of news cameras and makers, for which she acknowledged it it just was totally ridiculous,” Duncan charged. reporters – he did what he’s been doing for was a tactic to “get in front of competitors” “I can tell you this,” he continued, “his lawyer the past several months since the uproar over – although she claimed she knew nothing better advise him a little bit because a jury Daraprim started: He tweeted. about the value of being first on the market would love to convict somebody if he acts “Hard to accept that these imbeciles with a product. that same way while he’s on trial.” represent the people in our government,” Valeant’s Schiller was not only on the hot Duncan was referring to Shkreli’s Dec. 17, Shkreli posted on Twitter. seat for the significant increases in the prices 2015 arrest in which he was charged with Trying to explain Shkreli’s behavior, Brafman of Nitropress (sodium nitroprusside) and defrauding investors in his former hedge told Scrip in a statement his client “meant no Isuprel (isoprenaline) and some of the firm’s funds, MSMB Capital Management and MSMB disrespect, but in truth, statements made by other practices that’s landed it in trouble with Healthcare, and misappropriating more than some of the members of the committee were federal and state investigators, but also for his $11m in assets from another of his former wrong, unfair and difficult to listen to without $400,000 per month salary and the fact he firms, Retrophin Inc., in what prosecutors responding.” hauled in about $27m in 2014, for which he called a “Ponzi-like scheme.” He said that although Shkreli “followed acknowledged he was “incredibly fortunate” and Before Shkreli left the hearing room, Rep. my advice about making no statements at “well compensated” for his work at the company. Trey Gowdy (R-SC) tried his best to get the the hearing, it was very frustrating for him Unlike Shkreli, Schiller remained stone- former drug exec to talk, even bringing up his to listen to what he believed to be patently faced throughout the hearing, but answered much-publicized $2m Wu-Tang Clan album false statements about Turing that he could lawmakers’ questions – even admitting to try to provoke a response. But Shkreli again not respond to because of the pending Valeant had “made mistakes,” but insisting the invoked his Fifth Amendment rights. criminal charges.” company has listened to the criticism and Gowdy – who became infamous for visibly Appearing later on CNBC’s Closing Bell, implemented changes. sweating throughout the 11 hours the Select Brafman called Shkreli’s “imbeciles” tweet “Like most other pharmaceutical companies, Committee on Benghazi, which he chaired, “unfortunate” and a “regrettable choice of we will from time to time raise prices,” Schiller grilled a calm and collected former Secretary words.” said. But he said Valeant expected its hikes of State Hillary Clinton this past October – The lawyer, however, defended his client to be “within industry norms and much did, however, get Shkreli to answer a “Yes, sir” as a “genius” and a “scientist,” even though he more modest than the ones that drew this when the lawmaker asked if he’d used the holds no scientific degrees – graduating with committee’s legitimate concern.” correct pronunciation of the former Turing a bachelor’s degree in business administration Turing’s Retzlaff, however, spent much of CEO’s last name. from Bernard M. Baruch College of the City her time arguing her company had done To that, Gowdy remarked, “See, you can University of New York. nothing wrong – contending most patients answer some questions. That one didn’t who are treated with Daraprim get it in the incriminate you.” The Rest Of The Story hospital and are covered by insurance or But Shkreli responded “I intend to follow the With Shkreli gone from the hearing, the can get it through the company’s patient advice of my counsel, not yours.” attention – and grilling – quickly turned assistance programs. Noting a New York broadcast station to the others on deck to testify: Turing’s She claimed two-thirds of the patients who interview Shkreli earlier had given, Gowdy chief commercial officer Nancy Retzlaff; need Daraprim get it for “one penny a pill” said “you couldn’t wait to come educate the Janet Woodcock, director of the FDA’s rather than the $750 the company charges. members of Congress on drug pricing. And Center for Drug Evaluation and Research Chaffetz, especially, chastised Turing for this would be a great opportunity to do it.” (CDER); Mark Merritt, president and CEO spending $23,000 on a yacht party for its sales “I’m vexed,” Gowdy said, noting Shkreli of the Pharmaceutical Care Management staff, while claiming it was operating at a loss. didn’t have to be “prodded” to talk during his Association, a trade group representing “You’re raking it in hand over fist,” Chaffetz TV interview or to tweet on Twitter or “show pharmacy benefit managers; and Howard said, pointing to the firm’s gross sales last us his life on that little webcam he’s got.” Schiller, the interim CEO at Valeant year of $98m and net sales of $20m – all from At one point, Shkreli’s high-powered Pharmaceuticals International Inc., who took Daraprim. New York lawyer Benjamin Brafman tried to over for an ailing Michael Pearson. He also highlighted the fact that since intervene, asking to be recognized. Woodcock’s agency was condemned by Turing was founded last year, salaries for But Jason Chaffetz, chair of the Oversight lawmakers for its generics backlog, for which some executives jumped several hundred Committee, quickly gave Brafman a stern “No, she attributed to an “explosion” in applications thousand dollars – with one going from you are not recognized and you will be seated.” – declaring the FDA was a “victim of our own $160,000 to $800,000. Cummings told Shkreli he could “go down success,” with the copycat industry growing Chaffetz and Cummings and the other in history as a poster boy for greedy drug “like a factory with a great product.” But, she lawmakers, however, made it clear it’s not company executives or you could change lamented, the agency’s resources didn’t keep up. just Turing and Valeant that were being the system.” The CDER chief, who had just testified a scrutinized by Congress – it’s all of the “Yeah, you,” Cummings told a toothy week earlier before a Senate panel on the biopharmaceutical industry’s pricing practices grinning Shkreli. “Are you listening?” matter, insisted the FDA was “catching up” that are in the spotlight. The tactics used by Shkreli’s lawyer quickly instructed him to on its backlog. Turing and Valeant, Cummings asserted, “are say “Yes.” “We’re doing a great job,” Woodcock declared. not limited to a few bad apples.” Cummings told Shkreli he truly believed “you Lawmakers also pressed Woodcock about “They are prominent throughout the entire could become a force of tremendous good.” the use of the tropical and rare pediatric industry,” he said. But after Shkreli left the hearing – followed diseases priority review vouchers by drug [email protected]

6 February 12th 2016 @scripnews scripintelligence.com © Informa UK Ltd 2016 policy & regulation briefs Policy & Regulation Briefs Gilead Moves To Block Harvoni Infringer In India Gilead Sciences has moved court to block an alleged copy of its blockbuster hepatitis C treatment, Harvoni (sofosbuvir/ledipasvir), in

India which it believes not only wrongly rides Tashatuvango/shutterstock.com on the brand name but may also not have the requisite regulatory approvals. Gilead said that it discovered Bombay Pharmaceuticals advertising on its website its purported formulation of a combination of sofosbuvir and ledipasvir product under the brand name Harvobay which is deceptively similar to its well-known and registered trademark Harvoni. which regulators late last month again pledged to sponsors and investigators that “any event causing In its case before the Delhi High Court, Gilead get done this year. Pitts also noted a rule finalized the hospitalization of a healthy volunteer in a trial noted, among a string of arguments, that the this past November by the Centers for Medicare should be deemed a ‘new fact’ and should be “invented” word Harvoni is capable of being and Medicaid Services, which lumps biosimilars notified without delay to the health authorities.” accorded the “highest degree” of protection referenced on the same innovator into the same under trademark law. “In fact the prefix Medicare Part B reimbursement rate. CMS said it UK Approves Gene-Editing Harvo also ascribes no meaning to it and plans to use a single average sales price payment Of Human Embryos is synonymous with the plaintiff’s product. limit for biosimilars that are assigned to a specific The UK’s fertility regulator has backed a scientist’s Given the various articles, journals and healthcare common procedure coding system request to edit the human genetic code in an effort to fight inherited diseases, despite the publications about the drug’s success, grant of code – often referred to as J codes for drugs. The rule, Pitts said, sets the stage for how the Medicare ethical issues such medical research will raise. regulatory approvals, commercial partnership program will reimburse for biosimilar products. The regulator, the Human Fertilisation and etc. since and the prior adoption and Embryology Authority (HFEA), gave its approval extensive use of the trademark Harvoni, the French Trial Tragedy: on Feb. 1 and the research work could begin in plaintiff has exclusive rights under common Three ‘Major Failings’ just a few months. It is the first time a country law to use the said mark and to prevent its An interim report by French government has considered the DNA-altering technique in misuse in the hands of the third party,” Gilead’s inspectors has identified three “major failings” in embryos and approved it. The research will use counsel said. Gilead argued that the use in the conduct of the Phase I trial run by the CRO gene-editing techniques and be carried out at any manner of the impugned mark by a third Biotrial that led to the death of one volunteer and the newly established Francis Crick Institute under party will contravene the “public recognition the hospitalization of five others with suspected the leadership of Kathy Niakan. Her intention is neurological damage. The report, by the General to understand the genes that human embryos and association” of the trademark Harvoni or Inspectorate for Social Affairs (IGAS), took issue need to develop successfully, the institute said. prefix Harvo with it and with the recognition with Biotrial’s decision to administer further The regulator, HFEA, in a terse statement said: “our of it as the proprietor of the mark Harvoni. doses of Bial’s FAAH inhibitor, BIA 10-2474, to licence committee has approved an application Harvoni and Sovaldi (sofosbuvir) raked in other participants without telling them that the from Dr Kathy Niakan of the Francis Crick Institute global sales of $4.9bn (+27%) in the fourth first volunteer had been taken to hospital the to renew her laboratory’s research licence to quarter of 2015. day before and without seeking their consent to include gene editing of embryos. The committee continue in the study. It also questioned the delay has added a condition to the licence that no Lawmakers To Examine Biosimilars in notifying the authorities of the adverse events. research using gene editing may take place until Law Progress IGAS said it would continue its investigations by the research has received research ethics approval. The House Energy and Commerce Subcommittee looking at the reliability, quality and source of As with all embryos used in research, it is illegal on Health wants to look under the hood and see the preclinical data on the product, and would to transfer them to a woman for treatment.” It how things are going with the FDA’s progress in be recommending ways of tightening up on the did not elaborate. The Francis Crick Institute in a implementing the 2010 law that gave the agency conduct of first-in-human trials. It also called for statement said that Dr Niakan and her team will be the authority to approve biosimilars – Biologics an international forum of independent experts looking at the first seven days of a fertilized egg’s Price Competition and Innovation Act (BPCIA) – and regulators to be established to discuss issues development, from a single cell to around 250 and plans to convene a Feb. 4 hearing. The head surrounding the reporting of adverse events in cells. Mission has built a platform to discover and of the subcommittee, Rep. Joe Pitts (R-PA), said the Phase I studies. The regulatory agency ANSM, develop first-in-class small molecule drugs that panel also will examine the status of the Biosimilar which gave the go-ahead to the study last year, selectively target deubiquitylating enzymes (DUBs), User Fee Act program, which was enacted in is conducting its own investigation into the which are involved in multiple cellular processes 2012 as part of the FDA Safety and Innovation affair, and said that the new committee it has including DNA damage and cell proliferation. Act to support the agency’s work related to the set up to look at the clinical and preclinical data Inhibiting the enzymes could help treat cancer and development, review and approval of those on the drug would hold its first meeting on Feb. other diseases such as neurodegenerative disease, products. Pitts also pointed out the FDA has issued 15. Noting that the IGAS inspectors had not muscle wasting and infectious disease. Although several guidances, but sure to come up at the identified the direct causes of the incident, the DUBs are recognised as playing an important role hearing are three other guidances the agency has health minister, Marisol Touraine, said that the in pathological processes, the major hurdle to date so far failed to produce: interchangeability, labeling inspectorate would produce a final report by the has been to develop drugs to target individual and statistical approaches to analytical similarity, end of March. In the meantime, she informed all DUBs selectively.

© Informa UK Ltd 2016 @scripnews scripintelligence.com February 12th 2016 7 headline news FDA ‘Moon Shot’ Center To Expedite Combo Cancer Drugs “The administration has taken a significant Pediatric Cancer Research step that we hope will enhance the Under the moon shot initiative, the FDA’s ability to execute their vital role in administration also plans to make pediatric translating scientific discovery into new cancer research a priority – intensifying therapies for patients,” said Ellen Sigal, efforts to collect and analyze tumor FOCR’s founder and chair. specimens from the rarest childhood cancers

PathDoc/shutterstock.com and enlisting participation from the pediatric Taxpayer Support oncology community. The advocacy group Research!America said In a Feb. 1 Twitter chat, Lowy pointed a survey it commissioned found that half of out his agency plans this year to launch Americans who responded to the poll said a pediatric counterpart of the NCI-Match they wouldn’t mind a tax increase to fund the study, which is aimed at matching the most moon shot initiative, while 38% said they’d be appropriate targeted therapy or combinations reluctant to the idea, with 12% unsure. of treatments to patients based on the The White House on Feb. 1 said President Barack Of those who favored a tax increase, 57% said molecular profile of their tumors. Obama plans to spend $1bn to jumpstart his they would be willing to pay up to an added The NCI-Match study, launched last “moon shot” initiative to end cancer – a project $50 per year in taxes to support the project. summer, is expected to be the largest being led by Vice President Joe Biden, who lost “Americans understand that we must precision medicine clinical trial in history. a son last year to a brain tumor. turbo-charge our investments in cancer The trial currently is in the interim analysis The bulk of those funds, $755m, Obama research in order to make significant headway phase – having paused this past November doesn’t yet have in hand, but plans to ask for it in our battle against this insidious disease,” after reaching 800 participants, which far- as part of his fiscal year 2017 budget request, insisted Mary Woolley, president and CEO of surpassed the 500 expected for the initial which is expected to be unveiled Feb. 9. Research!America. phase, an NCI spokesperson told Scrip. For now, the project will rely on $195m from Also being created as part of the moon the FY 2016 funding Congress granted to the shot initiative is the “Vice President’s Task Force National Institutes of Health (NIH), which got Exceptional Opportunities in Cancer Research The White House revealed the first details a $2bn boost – the largest annual increase the Fund,” which will be focused on high-risk, of the president’s initiative on the same agency has had in more than a decade. high-return research identified by the day Biden led the first meeting of the Among the projects being launched collaborative work and new ideas stimulated White House Cancer Moon Shot Task Force, as part of the moon shot initiative is a by the research community. which Obama created last week under an new $75m FDA “virtual” Oncology Center executive memorandum. of Excellence, which is being created to Immunotherapies Collins, Lowy, Health and Human Services expedite the development and regulatory The White House said the administration Secretary Sylvia Mathews Burwell and Robert review of new combination therapies to plans to use some of the $1bn to speed the Califf, whose nomination to be commissioner treat cancer – a key goal of the program, development, evaluation and optimization of of the FDA currently is being held up by a which was first announced by Obama during safe cancer vaccines targeting unique features handful of Senate holds imposed last month, his Jan. 12 State of the Union address to of individual cancers. are among those serving on the task force. Congress and the American people. It also wants to invest in improving cancer It also includes leadership from the The FDA center, the White House said, immunotherapies, so that patients with Department of Defense, the Department will be expected to leverage the combined all types of tumors can benefit from those of Commerce and the National Science skills of regulatory scientists and reviewers products – a particular aim for NIH Director Foundation, among several other agencies. with expertise in biopharmaceuticals and Francis Collins and National Cancer Institute The funds to run the task force also are devices – supporting an integrated approach acting chief Douglas Lowy. coming from the NIH’s budget. to evaluate products to prevent, screen for, Collins noted during a media briefing The task force is required to post reports diagnose and treat cancer. last month that while immunotherapies online about its functions and activities, The FDA’s oncology center also will be have been successful in treating leukemia, thereby being transparent to the American charged with developing and promoting the lymphoma, lung and kidney cancers and people, Obama said in his executive memo. use of methods created through precision melanoma – pointing to president Jimmy The president also charged the task force medicine – the focus of another of Obama’s Carter’s recent revelation that his metastatic with producing a report by Dec. 31 with initiatives, which was launched early last year, melanoma that had spread to his brain has its findings and recommendations and with the NIH taking the lead. appeared to disappear after treatment with submitting it to the White House. The non-profit advocacy group Friends Merck & Co.’s checkpoint inhibitor Keytruda The moon shot program, the White of Cancer Research (FOCR) declared it was (pembrolizumab) – the products haven’t been House said, will require scientists, cancer “thrilled” about Obama’s and Biden’s plan for as successful in other types of tumors, like physicians, advocates, philanthropic the FDA virtual oncology center – something pancreatic, brain, prostate and breast cancers. organizations and representatives of the group itself earlier asked Congress to And for the tumors where there the biotechnology and pharmaceutical create to improve coordination within and have been the dramatic responses with industries to work together to focus on between the agency’s medical product immunotherapies, those positive outcomes major new innovations in the understanding centers and to “break down decades’ old silos” have not always been sustained, the NIH of and treatment for cancer. for greater efficiency. chief lamented. [email protected]

8 February 12th 2016 @scripnews scripintelligence.com © Informa UK Ltd 2016 headline news

Woodcock: Biosimilars Program Can ‘Moon Shot’ Lift Will Explode FDA Out Of Its Silos? Janet Woodcock, director of the FDA’s Center with sponsors and provides written advice Even though the White House’s “moon for Drug Evaluation and Research (CDER), for ongoing development programs and shot” initiative is focused on cancer, a told lawmakers on Feb. 4 she was concerned then continues to meet with those who key component of the program – a new the agency’s biosimilars program “is going are interested in taking their biosimilars multimillion-dollar FDA “virtual” center to explode” because it lacks funding and forward. But the meetings have added to for excellence intended to expedite the resources, with the anticipation the agency the FDA’s workload. development and regulatory review of new could be facing a multitude of applications it’s Indeed, the number of biosimilars meeting combination therapies – may be the force unprepared to handle. requests shot up 81% since BsUFA was to lift the agency out of its silos so that “I’m concerned we will not have the staff enacted – leaping from 32 in FY2013 to 58 in drugs, devices and diagnostics intended to because we’re always waiting to catch up,” FY2015. The number of scheduled biosimilars be used together for other types of diseases Woodcock told the members of the House meetings also rose 67% – jumping from 30 in are not forced to undergo time-consuming Energy and Commerce Subcommittee on FY 2013 to 50 in FY2015. separate assessments, said Ellen Sigal, Health. She noted that when Congress The FDA also provided written advice to founder and chair of the advocacy group created the US biosimilars pathway in 2010 sponsors for 16 out of 23 meeting requests Friends of Cancer Research (FOCR). under the Biologics Price Competition and that were denied or cancelled due to Manufacturers involved in developing Innovation Act (BPCIA), which was enacted incomplete or premature requests. All of drug-device combos have long as part of the Affordable Care Act – President those meetings are on the FDA’s back without complained those products get hung up Obama’s healthcare law – it didn’t appropriate any help from Congress to support the in the regulatory process because the any additional funding for the FDA to carry time and resources going into those efforts, FDA center that doesn’t have the primary out the program. Woodcock pointed out. review responsibility doesn’t consider it a Two years later, lawmakers did pass the “You need some kind of an appropriation,” priority and puts the application on the Biosimilars User Fee Act (BsUFA), which allowed Rep. Frank Pallone (D-NJ), ranking member backburner. A lot of that has to do with the FDA to collect fees from applicants to on the E&C Committee, told Woodcock. how user fees are paid. support the review process, although because “Having the industry pay a fee is not good Jay Siegel, chief biotechnology officer there was no existing biosimilars market at the enough.” and head of scientific strategy and policy time, the agency had to take $20m from other Clearly, Woodcock said, had the FDA’s at Johnson & Johnson Inc., explained it last parts of its budget to use as a base to launch biosimilars program had more staffing and summer to Scrip this way: If a drug maker is the program, she explained. funding so that it could set things up at seeking approval of a medicine that requires Woodcock noted the agency collected the get-go, “we would have been better an auto-injector, the company pays the user $6m in fiscal year 2013, $13m in FY2014 and off now,” acknowledging the complaints fees to the FDA’s drug or biologics centers. $23.8m last year. “So we are beginning to from lawmakers the agency is running But the agency’s device center, which must build and as drugs get on the market we’ll be behind on issuing three critical guidances sign off on the auto-injector, won’t get any able to have perhaps more robust funding for – interchangeability, labeling and statistical user fees to speed its review, so therefore, this program,” she said. But she added, “This approaches to analytical similarity. Woodcock it doesn’t have the same timeline and program is not funded by appropriations.” said the agency “hoped” to have drafts of accountability obligations as the drug and She pointed out there are 60 proposed those out this year. biologics centers, ultimately holding up the biosimilar products to 18 different reference She said the FDA had received “many product’s entry to the US market. innovator drugs enrolled in the FDA’s opinions” from stakeholders on how Siegel said he’d like to see a user fees Biosimilar Product Development (BPD) the labeling for biosimilars should be – structure established for drug-device program – the mechanism and structure for acknowledging the agency approved its first combination products, and considers collecting the development-phase user fees product, Sandoz Inc.’s Zarxio (filgrastim-sndz), getting that done an issue for the medical to support the review activities. before the agency had its policy in place. “We product industry. FOCR’s Sigal argued When a sponsor joins the BPD program will issue a draft and a final and get a policy that another driver that’s kept the FDA in and pays the associated user fee for a together and then all labels would conform to its silos, which slows down the reviews specific product development program, that that,” she said. of combination therapies, is the fact program is managed by the FDA per the Woodcock also said there’s been “quite a the agency’s review process is focused BsUFA performance goals and procedures. bit of discussion” about the interchangeability on individual products, rather than the diseases they are intended to treat. The number of sponsors in the BPD program guidance, “because companies may need The White House, so far, has released is not absolutely reflective of the overall to do the scientific work during their vague details about what it anticipates number of industry programs. Along with development program.” for the FDA’s virtual oncology center of those already in the BPD program, Woodcock Woodcock pointed out that the BPCIA excellence. The FDA provided little insight said there are “several dozen” more potential was considered to be self-implementing into establishing the moon shot center – candidates from firms that have “reached out for the FDA, without guidance. “We will although that may be because the White but not engaged in our process.” approve biosimilars regardless of whether House may have presented the agency “People are anxious to see more progress we have final guidance out or not,” she said, with only a concept and not a blueprint. and more certainty,” she said. although acknowledging that may “create Read the full story at: http://bit.ly/1NRTgJN Woodcock noted in her testimony the more ambiguity.” [email protected] FDA holds development-phase meetings [email protected]

© Informa UK Ltd 2016 @scripnews scripintelligence.com February 12th 2016 9 headline news

Pfizer’s Currency, Patent Pressures Boost Allergan (Continued from page 1) capital around the world,” Pfizer chair, president Newer Products Boost Sales in 2016 that will expand the drug’s label from and CEO Ian Read said during the company’s Pfizer’s top-selling products in 2015 were first-line treatment of advanced breast cancer earnings conference call. Lyrica (pregabalin), for which global sales to women with recurrent metastatic breast Pfizer reported $48.9bn in revenue and rose 9% year-over-year to $3.7bn, and Enbrel cancer. Ibrance also could win approval in the $2.20 in adjusted diluted earnings per share (etanercept), for which sales outside of the EU this year for newly diagnosed and recurrent (EPS) for 2015, which was about $500m US and Canada dropped 13% to $3.3bn. But metastatic breast cancer. above analyst consensus estimates for the biggest sales gains in Pfizer’s innovative One other potential drug approval in revenue and $0.01 above consensus for EPS. products business came from drugs that were 2016 is for ALO-02, an abuse-resistant, The company attributed the bulk of last year’s approved or won expanded labels or public extended-release co-formulation of revenue and EPS declines to unfavorable health endorsements within the past few oxycodone and naltrexone for chronic pain. foreign currency exchange rates, particularly years: Prevnar 13 (pneumococcal 13-valent The FDA extended its review of the pain in Venezuela, and the end of patent conjugate vaccine), Ibrance (palbociclib), drug candidate in November. protection for blockbuster drugs, such as Xeljanz (tofacitinib) and Xalkori (crizotinib). At least two other product candidates may Celebrex (celecoxib) for arthritis pain. be submitted for FDA approval in 2016: the Since Pfizer also will face currency and sodium glucose co-transporter 2 (SGLT2) patent pressures in 2016, the company’s Pfizer expects to take inhibitor ertugliflozin for type 2 diabetes, financial guidance for this year is $49bn a $2.3bn hit from foreign which is being developed in partnership with to $51bn in revenue and $2.20 to $2.30 in Merck & Co. Inc. and inotuzumab ozogamicin adjusted diluted EPS. It’s anticipated that currency exchange rates for acute lymphoblastic leukemia (ALL). newer products will contribute to sales growth as well as drugs and indications and experience losses due to Phase III Data This Year that may be approved this year, but large generic competition In addition to late-stage clinical trial readouts acquisitions also are important revenue for Ibrance in first-line advanced breast cancer, drivers for Pfizer. Worldwide sales grew 40% to $6.2bn for Xeljanz in psoriatic arthritis, and ertugliflozin Sales in the fourth quarter of 2015 jumped the Prevnar family of pneumococcal vaccines; monotherapy and fixed-dose combinations 7% to $14bn versus the same period in 2014, 70% to $523m for the rheumatoid arthritis with Merck’s Januvia (sitagliptin) and with including currency and competitive impacts, drug Xeljanz, an oral JAK inhibitor; and 11% to metformin, Pfizer expects to report Phase with a $1.2bn contribution from Hospira’s $488m for Xalkori, which is a kinase inhibitor III results for Sutent (sunitinib malate) as an products after Pfizer completed its purchase approved to treat ALK-positive metastatic adjuvant therapy for renal cell carcinoma of the company in September. non-small cell lung cancer. Ibrance, which patients, for dacomitinib in EGFR-positive Acquisitions also have been important to launched for certain breast cancer patients in metastatic NSCLC, and for its cholesterol- Allergan’s growth, since the company more February, generated $723m in sales last year. lowering agent bococizumab. than doubled its revenue during the first nine Prevnar sales have been growing since the Pfizer believes that its PCSK9 inhibitor, months of last year to $10.9bn versus $4.3bn Centers for Disease Control and Prevention which lags behind Amgen Inc.’s Repatha during the same period in 2014 following (CDC) recommended routine administration (evolocumab) and Praluent (alirocumab) from Actavis PLC’s $66bn purchase of Allergan. of the vaccine in older adults based on Regeneron Pharmaceuticals Inc. and Sanofi, The company will not report its full-year 2015 Pfizer’s CAPiTA data in patients aged 65 and could be a best-in-class biologic. Data from earnings until Feb. 22. up. However, Pfizer chief financial officer six Phase III studies may be revealed in 2016, Read insisted that the merger of Pfizer and Frank D’Amelio noted during the company’s including the SPIRE-SI trial in statin-intolerant Allergan will close as scheduled in the second earnings call that 2016 Prevnar sales are dyslipidemia. Pfizer said on Feb. 2 that SPIRE- half of this year without any delays caused by US expected to be about the same as in 2015. SI met its primary endpoint, but detailed policies that could prevent Pfizer from moving Xeljanz sales have grown at a double-digit results will be shared at an upcoming its corporate headquarters to Allergan’s Dublin, rate since the drug’s approval in 2012, but not medical conference. Ireland domicile to achieve a lower tax rate. as fast as investors would have liked, and the This year also could shed new light on “Under current law, I do not believe there company has trimmed its plans to expand Pfizer’s immuno-oncology strategy as is any reason why this deal will not close,” the Xeljanz label, although a once-daily data are expected for the PD-L1 inhibitor Read said. formulation for rheumatoid arthritis could win avelumab that’s being developed in UBS Securities analyst Marc Goodman said US FDA approval this year. partnership with Merck KGaA. Monotherapy in a Feb. 2 research note that Pfizer’s highest But Xalkori, which was first approved about data for Pfizer’s OX40 inhibitor and profile products performed well in 2015 and 14 months before Xeljanz’s initial indication, combination therapy results for the should do the same this year, but he expects is facing another potential approval in the US. company’s candidate that blocks 4-1BB also the Allergan transaction to add the most A supplemental new drug application (sNDA) may be reported in 2016. value to the company’s stock in 2016. is awaiting FDA approval for ROS1-positive However, Pfizer recently discontinued a “The key products are performing nicely as NSCLC after the European Commission (EC) Phase II clinical trial for PF-05212377 due to expected and, with the [revenue] guidance approved a label expansion for Xalkori in futility in patients with mild to moderate out of the way, now we expect the stock to November for advanced NSCLC to allow Alzheimer’s disease. PF-05212377 is a 5-HT6 trade much more on the anticipated Allergan treatment of newly diagnosed patients. receptor antagonist, which is the same type deal, which we still expect to be completed However, the first 10 months or so of Ibrance of drug as Axovant Sciences Ltd.’s Phase III in the second half of 2016 and be a positive sales outpaced Xalkori in its fourth full year on candidate RTV-101. catalyst for the stock,” Goodman wrote. the market. Pfizer anticipates FDA approval [email protected]

10 February 12th 2016 @scripnews scripintelligence.com © Informa UK Ltd 2016 headline news Alexion Rare Disease Launches Off To Slow Start Alexion Pharmaceuticals has successfully are still very low disease awareness for LAL- acquired two new drug approvals that will D, we’re observing both interest and activity expand its revenue base beyond its flagship among the physicians we are reaching.” drug Soliris, but analysts are showing little While both of these launches are still confidence in the underwhelming launches. particularly early, the trajectory of an initial The ultra-rare disease company announced launch usually foretells the success of a earnings Feb 3, admitting that the launches drug for the long-term. Analysts expressed of its two recently-approved drugs, Strensiq concerns about the slow ramp up for the two (asfotase alfa) and Kanuma (sebelipase alfa) new compounds. are both off to slow starts. “We believe that there is a real possibility of “While we have observed early progress, yod67/shutterstock.com these launches underperforming even these we continue to expect that the launch reduced expectations. This is mostly due to the trajectory for Strensiq will be slow and extremely low incident patient population and steady, consistent with the launch of almost non-existent prevalent population for therapies for ultra-rare diseases. This is due each of these therapies. While we are believers to the low incidence and high mortality of in the long-term potential of these therapies, HPP, as well as the very low awareness of the the near-term could be painful,” wrote BTIG disease,” said Alexion CEO David Hallal on a programs address the morbidities and high analyst Hartaj Singh in a note to clients. conference call with analysts. mortality of HPP.” Meanwhile, Morningstar analyst Stefan Strensiq is an enzyme replacement therapy The company noted that Strensig brought Quenneville wrote in a Feb. 3 note that he had that was approved by FDA in October for in about $12m in revenues during the fourth concerns about the lowered guidance the the treatment of perinatal-, infantile- and quarter. company offered for 2016, but still has hope juvenile-onset hypophosphatasia (HPP), a rare Alexion has been relying on its physician that these drugs will perform down the line. pediatric disease. education and diagnostic testing in hopes “We think that strong pricing and Alexion’s “In the U.S. we are pleased with the initial of identifying new patients for both Strensiq expertise in identifying patients will allow observations in the early stages of launch. and its more recently approved drug Kamuna, both drugs to eventually achieve blockbuster First, we are benefiting from having a which got the greenlight from FDA in sales and help diversify its ultra-rare-disease dedicated metabolic field team which enables December and launched in January. portfolio beyond Soliris,” he wrote. us to reach more physicians who are seeing “As the Kanuma launch is now under way in The company’s first product, which was patients at a higher likelihood of having HPP,” the U.S. and Germany. We’re applying our deep launched almost a decade ago, continued said Alexion chief commercial officer Carsten experience in ultra-rare diseases to serve the to do well as the company pursues other Thiel of the Stensiq launch so far. “Our team is large community,” added Thiel. “Following the indications for the drug. Soliris had sales of focused on overcoming the low awareness of Synageva integration, we enhanced the LAL-D $2.59bn in 2015, up from $2.1bn in 2014. HPP with our disease education initiative. Our disease awareness programs. Although there [email protected] Novo Nordisk Says Global Payer Pressure Limits Price Rises Novo Nordisk A/S says the pricing (DKK; $1.23bn) on net sales of DKK28.88bn, “The main driver for the top line will be environment for its drugs is getting more up 17%. introduction of new drugs,” the CEO said on difficult globally, not least in the US, but the The company said sales in the the call. “Typically, in the beginning of their Danish diabetes fighter hopes the launch of increasingly crowded US insulin market of introduction, they require fewer rebates, its once-daily, next-generation basal insulin its GLP-1 drug Victoza were curbed by whereas when they approach patent analogue Tresiba (insulin degludec) will help it Eli Lilly & Co.’s competing once-weekly expiration, rebates increase over time. So expand market share there. glucagon-like peptide-1 receptor agonist it’s new drugs which will be the driving The world’s biggest maker of insulin Trulicity (dulaglutide). component for us going forward.” unveiled fourth-quarter profit on Feb. 3 that “We are losing market to Trulicity,” Novo Novo Nordisk is thus banking on the launch marginally missed analysts’ forecasts. The Nordisk’s chief executive Lars Rebien of its next-generation diabetes treatment uncertain picture for 2016 prompted the Soerensen admitted on a call with journalists. Tresiba in the US, which the FDA approved Danish insulin maker to cut its long-term Victoza sales in last year’s fourth quarter came last September. The Danish group hopes financial target for operating profit growth in at DKK4.90bn, up 22% from the year ago to differentiate Tresiba, the follow-on for its to 10% from 15%. It clarified that it expects quarter but below analysts’ predictions of current basal insulin Levemir, from Sanofi’s operating profit to grow by 5% to 9% this around DKK5.08bn. long-acting insulins with a claim for reduced year, from an earlier guidance of mid to high Rebien Soerensen noted that insulin hypoglycemia, which it plans to file for in 2016, single-digit growth. makers have been under a lot of pressure based on data from the Phase III SWITCH 1 and Still, group net profit in the fourth quarter recently. Pricing flexibility in the US, the SWITCH 2 trials in type 1 and type 2 diabetes. of 2015 rose a strong 26% from the same world’s biggest pharmaceuticals market, is Novo Nordisk on Jan. 29 reported positive year ago quarter, to 8.26bn Danish kroner severely constrained. data from the SWTICH 2 program in which ➤

© Informa UK Ltd 2016 @scripnews scripintelligence.com February 12th 2016 11 business bulletin Business Bulletin significant downward slide below $2 per share last losses elsewhere in the portfolio, including for its Canada’s Price June when its lead drug candidate, the Alzheimer’s top-seller Januvia (sitagliptin). A quarterly sales disease compound ELND005, failed in mid-stage decline for the diabetes drug was attributed both Negotiators On Where testing. After its failure in Alzheimer’s disease, to foreign exchange effects and heavy US buying Firms Go Wrong Transition put all its hopes into newly minted of the product during the third quarter, the New If your company wants to sell its products lead candidate TT401, a GLP-1 and glucagon Jersey-headquartered pharma reported. Merck had receptor agonist meant for the treatment of type worldwide product sales of $10.2bn in the quarter, on Canada’s publicly funded drug plans, 2 diabetes. Transition licensed the rights to the down 3% year-over-year. Impact of foreign exchange then it will likely have to do business with drug from Lilly in 2010 and brought the drug caused a 7% decrease in sales, while the effects of the pan-Canadian Pharmaceutical Alliance. through Phase I testing on its own. Lilly opted acquisitions and divestitures produced a 3% positive, This is the body that negotiates drug prices back into the program in 2013 and has been the company said. Full-year 2015 sales totaled for provincial and territorial drug plans and handing all development responsibilities. Transition $39.5bn, down 6% from 2014, but foreign exchange which has ensured that product listing contributed $14m to the Phase II development had a 6% negative impact, and acquisitions and agreements have become a prerequisite for program. The Indiana pharma paid $1m upfront divestitures produced a 3% negative impact. CEO securing drug funding across the Canadian and another $7m to Transition when it took of Kenneth Frazier claimed the overall takeaway is a market. The pCPA’s Brad Alyward, from Nova the license of the product. Should TT401 be story of Merck returning to growth on the strength Scotia’s Department for Health and Wellness, commercialized, Transition would gain another of new portfolio additions. “Despite strong currency $240m in milestone payments as well as royalties. headwinds, we were able to deliver growth in 2015 and Sherry O’Quinn*, from the Ontario Public The biotech announced that a Phase II study of and we expect to deliver growth again in 2016,” he Drug Programs Division, spoke to Scrip about 420 patients testing TT401 in four different doses told the Feb. 3 earnings call. “In fact, 2016 represents the perils of trying to charge too high a compared with placebo and an active comparator the first year in several years in which Merck’s new price and the future of evidence generation- arm was positive. The 24-week study showed that product sales growth, driven primarily by Zepatier, based agreements. The pCPA has changed TT401 lowered HbA1c levels by 1.43, statistically our new hepatitis C product, and Keytruda, are the landscape for companies wishing to significant compared with placebo. It also expected to contribute meaningfully above the do business in Canada. No longer do they reduced weight by 3.3kg at the highest dose, also impact of the products that are losing exclusivity.” negotiate with sixteen or so separate public statistically significant. Editas, BeiGene Offerings drug plans and no longer can they cherry pick Emerging Markets Holding Up, Redeem US IPO 2015? the major markets first. Meanwhile, its product Takeda Pursues Turnaround US initial public offerings by biotechnology listing agreements (PLA) have essentially Takeda continues to insist that its generics-hit companies in 2015 dried up in November, but since become the gateway for companies to get business is being successfully turned around Editas Medicine Inc. and BeiGene Ltd. had strong their drugs on to publicly funded plans. on the back of strong growth for new drugs offerings to kick off February, does that mean that However, it should be noted that a PLA by no in gastroenterology and oncology, as well as dozens of drug developers will be able to go public means obliges a province to buy the drug, emerging markets, which together now account again in 2016? Since no biotech firms attempted but if the pCPA declines to negotiate, then for around half of revenues. Insisting that the an IPO in December or January, two offerings it is much harder for companies to secure latest results confirm the turnaround of Takeda is probably aren’t enough to measure the market for coverage. And, coincidentally or not, the continuing after the major patent losses of the last biotech offerings this year. Still, the fact that Editas number of PLAs negotiated in the private few years, Takeda president and CEO Christophe gained 13.8% by the end of its first day of trading Weber said the major Japanese pharma firm “is and BeiGene jumped 18% clearly provided some healthcare market has increased in recent on the right track to deliver revenue growth and much-needed confidence for investors that back years. Back in 2010 the pCPA was set up to help improved profitability.” The results seemed to therapeutics companies. The Nasdaq Biotechnology Canada’s provinces get better value for money largely bear out this view, with the three growth Index (NBI) closed 1.2% higher on Feb. 3 even when buying drugs and to ensure improved pillars logging combined growth of around though the broader Nasdaq index closed down and more consistent access to medicines. 9% in the period, despite what acting CFO 0.3%. And, at this point of 2016, every day of It was allocated no formal office and was Rudolph van Houten described as a “very volatile positive activity for the NBI is worthy of celebration staffed by employees from provincial health environment” in the emerging markets segment. for investors with significant holdings in drug departments who took up the work in their The company’s reported group revenues rose by development companies, since the biotech index is spare time. Despite the limits on resources, by 4% to JPY1,393.3bn ($11.80bn) in the fiscal nine down 33.3% from last year’s peak on July 20 and it the end of December 2015 it had completed months ended Dec. 31, with underlying growth up has fallen 19.5% so far this year. As for the IPO class by around the same percentage and forex effects of 2015, the numbers are even worse: If an investor 89 negotiations relating to branded products from a weaker yen adding around JPY20bn to the bought stock in every single first-time offering by with 24 still ongoing. Those figures will likely top line. In what he said was “a good quarter,” van a therapeutics firm last year, their average return increase as the pCPA has opened an office in Houten stressed that “emerging markets continued was just 3.6% by Dec. 31. And so far in 2016, returns Ontario and is taking on dedicated staff – it to perform well” despite the challenges “that have fallen to a dismal -21.3% as of the end of hired two people at the end of 2015 and plans everybody knows about,” although he did concede January versus the drug makers’ IPO values. to employ three more soon. growth “was at a slightly lower rate, which was no surprise given the market turmoil.” Gilead HCV Sales Decline In US Transition Results Not Good Strong sales growth continues almost unabated at Enough For Lilly? Merck Points To Keytruda, Gilead Sciences Inc., but the virology powerhouse Transition Therapeutics tanked on Feb. 1 after Zepatier Promise reported that domestic sales for its hepatitis C announcing largely positive results for its Merck & Co. Inc. urged investors to basically look drugs actually decreased by 26% year-over-year diabetes candidate due to investor worry that big past a flat fourth quarter 2015 performance on during the fourth quarter. The decline, however, pharma partner Eli Lilly & Co. may not choose to Feb. 3, emphasizing the promise of its cancer was more than offset by hepatitis C virus (HCV) commercialize the program. The biotech’s stock immunotherapy Keytruda (pembrolizumab) and drug sales growth in the rest of the world, including took a major hit, dropping as much as 30% to its just-approved hepatitis C combo Zepatier a blockbuster launch of Harvoni (sofosbuvir/ trade below $1 per share. The stock began its (elbasvir/grazoprevir) to begin to offset revenue ledipasvir) and Sovaldi (sofosbuvir) in Japan.

12 February 12th 2016 @scripnews scripintelligence.com © Informa UK Ltd 2016 headline news Novo Nordisk Says Global Payer AstraZeneca Under Pressure But Pressure Limits Price Rises (Cont’d from p11) Tresiba demonstrated it was better at $45bn Target ‘Still Achievable’ lowering rates of abnormally low blood AstraZeneca’s business is under two key While the PDL1-positive space is “very sugar events than insulin glargine was in pressures as it enters 2016, CEO Pascal Soriot competitive” it only encompasses 25-30% people with type 2 diabetes. In the SWITCH explained during the company’s fourth of patients, claimed Soriot. AstraZeneca is 2 study of 721 type 2 diabetes patients, quarter and full year 2015 presentation: the working on the assumption there is still huge Tresiba reported a statistically significant “enormous headwinds” created by the US opportunity in lung cancer in the PDL1- 30% lower rate of confirmed symptomatic patent expiry of Crestor this year and the negative space. However, “BMS has said that hypoglycemia than Lantus. And the dilutive effect of the ZS Pharma and Acerta around 70% of first-line NSCLC patients are observed rate of nocturnal hypoglycemia Pharma acquisitions. AstraZeneca reported PDL1-positive,” Bernstein analysts noted. was 42% lower than Lantus, also statistically fourth quarter and full-year numbers broadly significant. in-line with expectations, meeting guidance Diabetes Update “We are [also] waiting for SWITCH 1 data for 2015. AstraZeneca said it would refile the NDA for and if they are of a similar nature we will AstraZeneca’s growth ambitions in its new diabetes combination drug saxa/dapa consider submitting a supplemental NDA oncology are being driven by new products (a fixed-dose combination of saxagliptin and based on those two trials,” Krogsgaard Lynparza and Tagrisso. It’s still “early days” for dapagliflozin) with the FDA in the first half of Thomsen. Those headline results of SWITCH 1 ovarian cancer drug Lynparza, said Soriot, but this year following a complete response letter are expected later in the first quarter of 2016. noted that there had been a 10-fold increase in October 2015. The new filing will include in BRCA testing rates over the past 12 months additional clinical data that the company was so revenues would continue to accelerate. already in possession of. “This could enable The uncertain picture prompted Sales of Lynparza were $94m in 2015, approval before the end of 2016 and should the world’s biggest maker following a December 2014 launch. be viewed positively given its importance Tagrisso, dubbed “a cornerstone in our to AstraZeneca’s diabetes franchise growth,” of insulin to cut long-term oncology pipeline and our lung cancer noted Deutsche Bank analysts. strategy,” was approved for lung cancer by However, Soriot said that AstraZeneca still financial target for operating European regulators last week and in the US saw a lot of short-term potential in the SGLT2 profit growth to 10% from 15% two months ago. Tagrisso targets patients inhibitor dapagliflozin alone (Forxiga/Farxiga). with the T790M mutation. Soriot believes the Sales were up 137% in 2015 to $492m. “When But analysts say the SWITCH 2 data so drug had the “fastest development in history” we market the combination, it will be as a far shows only a modest advantage for of a pharmaceutical, and was discovered and separate brand,” he remarked. “We don’t want Tresiba versus Lantus, and that it remains developed in the UK, he highlighted. It first our sales team to lose focus,” so for now they unclear whether the benefit will be entered clinical testing in 2013 and was filed are just being asked to focus on dapagliflozin. recognized by payers. on the basis of positive Phase II data in under “While the results are encouraging, it will 500 patients. Sales of Tagrisso were $19m in M&A be important to see more details, such as on 2015, following a November launch, but with Soriot said any acquisitions that AstraZeneca numerical efficacy and severe hypoglycemia only 10% of relevant patients currently being looked at in the near term would have – and it remains to be seen what SWITCH 1 tested for the T790M mutation, he expects to be “accretive” because “our pipeline is shows in type 1 diabetics, who generally are significant growth as testing rates increase. full enough.” On deal size, “We’re agnostic more aggressive about tight control,” said Soriot acknowledged the competitiveness provided it is strategically aligned and the Peter Chang, principal scientific analyst at of the immuno-oncology space, and reiterated price is right,” added Soriot. BioMedTracker. that AstraZeneca was late to enter the field “People shouldn’t get lost in the woods Chang noted that in the pivotal type but intended to combat that by focusing on of whether it will be plus or minus 2% EPS 1 diabetes trials, there was no benefit on combination therapies. “A few years ago we next year,” he suggested. “People should ask, overall confirmed hypoglycemia, though in had almost nothing in oncology, and now we what will the company look like in a year the European label, a benefit on nocturnal have a very strong pipeline,” he said. or two, what’s the long term future?” He hypoglycaemia is noted. He also reiterated AstraZeneca’s ambition to acknowledged that “protecting” AstraZeneca’s “If SWITCH 1 does show a benefit on target annual sales of at least $45bn by 2023, EPS was going to be a challenge, and overall or nocturnal hypoglycemia, it would up from $24.7bn in 2015. bringing the company’s SG&A costs would of course bolster the case for the FDA to be a key strategy in achieving that goal, as make a label change to include comparative PDL1 AstraZeneca’s SG&A costs as a percentage of hypoglycemia information, though the Soriot confirmed that AstraZeneca had sales was “relatively high” compared with its company has expressed a fair degree of discontinued investigating durvalumab as a peers. “There is substantial reduction in SG&A uncertainty over what the FDA wants to see,” monotherapy for PDL1-positive non-small cell for us to achieve. The question is: at what Chang said. lung cancer in the ATLANTIC trial. “The question speed do we achieve this? To achieve it too With its launch in the US, Tresiba is now was: would we be able to take advantage of an fast may actually threaten the top line goals.” available in 39 countries. It is being withheld accelerated approval with data from ATLANTIC? He noted that AstraZeneca had the top from the German market, however, because The answer was no. Once another product has TSR (total shareholder return) value of the of disagreement over the drug’s pricing in achieved full approval, then an accelerated large cap FTSE 100 companies. “Shareholders Europe’s biggest drug market. approval is not an option [for anyone else]. The recognize our progress,” he believes. [email protected] field moved on very quickly.” [email protected]

© Informa UK Ltd 2016 @scripnews scripintelligence.com February 12th 2016 13 headline news Mersana/Takeda Deal Adds To ADC Pipeline Mersana Therapeutics is getting a vote of linker to an antibody that is delivered directly has more than doubled over the last five years. confidence from long-time partner Takeda to cancer cells, allowing for less damage to According to Citeline’s Pharmaprojects, there Pharmaceuticals as the two companies expand surrounding healthy cells. are currently two ADCs in Phase III and another their collaboration in antibody-drug conjugates Only three ADCs have ever reached the 21 in Phase II, as well as 30 more compounds and plan to move a molecule into the clinic. market – Pfizer’s Mylotarg (gemtuzumab in Phase I. Both the Phase III drugs were in that The biotech announced Feb. 3 that Takeda ozogamicin), which was later withdrawn; phase of development when Mersana and will pay $40m upfront for rights to XMT-1522, Roche’s Kadcyla (trastuzumab), an ADC of Takeda signed their initial deal in April 2014, an antibody-drug conjugate (ADC) that targets the blockbuster Herceptin; and Takeda’s but the mid-stage pipeline has ballooned – HER2. Mersana will receive another $20m once own Adcetris (brentuximab), developed by there were only 15 compounds in Phase II at an IND is accepted by FDA, which is expected ImmunoGen. the time. Seattle Genetics and ImmunoGen in mid-2016. Mersana will be responsible for are leading the development of ADCs, with preclinical and Phase I work, while the pair ADC Resurgence 22 and 10, respectively, active compounds in intend to work together on development After some struggling, the compounds are development. beyond that point. Mersana retains US and making a resurgence – the pipeline for ADCs [email protected] Canadian rights to the drug, with Takeda taking responsibility for rest-of-world Late- and Mid-stage ADC Pipeline commercialization. Phase Drug Originating and Licensing Cancer Indication Beyond XMT-1522, the two companies Companies will develop drugs using Mersana’s Fleximer Phase III moxetumomab pasudotox AstraZeneca/ Genencor Hairy cell leukemia ADC platform against targets that Takeda selects. The biotech will have the option to Phase III inotuzumab ozogamicin Pfizer/ UCB Acute lymphocytic leukemia co-development and co-commercialize one Phase II glembatumumab vedotin Celldex Therapeutics/Amgen/ Breast cancer, Melanoma molecule of its choice that comes out of the Seattle Genetics collaboration. All told, Mersana is eligible for Phase II milatuzumab-doxorubicin Immunomedics Myeloma, Non-Hodgkin’s lymphoma, $750m in milestone payments. Chronic lymphocytic leukemia XMT-1522 will be tested in four groups of Phase II L-DOS-47 Helix BioPharma NSCLC patients – those with breast, gastric and non- small cell lung cancers, as well as patients Phase II PSMA ADC Progenics Pharmaceuticals/ Prostate Seattle Genetics that have shown resistance to currently HER2- targeted therapies. The company wants to Phase II coltuximab ravtansine ImmunoGen/Sanofi Non-Hodgkin’s lymphoma, concentrate on low-expressing HER2 patients Acute B-cell lymphoma that do not respond well to many of the Phase II indatuximab ravtansine Biotest/ImmunoGen Myeloma currently available treatments. Phase II denintuzumab Seattle Genetics Non-Hodgkin’s lymphoma This will be the first molecule that the Phase II isactuzumab govitecan Immunomedics NSCLS, Breast, Gastric, Colorectal, Liver, pair move into the clinic, but far from its first NSCLC, Pancreatic, Prostate, Head and partnership. Takeda and Mersana initially neck, Renal, Ovarian, oesophageal, teamed up in April 2014. The original deal Bladder, Cervical, Endometrial allowed Takeda to use the Fleximer platform Phase II labetuzumab govitecan Immunomedics Colorectal for a small number of targets. That partnership Phase II HuMax-TF GenMab/Seattle Genetics Ovarian, Cervical, Oesophageal, was later expanded in January 2015 and again Endometrial, Bladder, Prostate, Head now. Mersana CEO Anna Protopapas told Scrip and neck, NSCLC that Mersana could gain almost $1bn from Phase II Resimmune Angimmune Cutaneous T-cell lymphoma, Takeda through all three iterations of the deal Melanoma, Acute lymphocytic and another $1bn in other partnerships. leukemia Protopapas has seen both sides of this deal Phase II mirvetuximab soravtansine ImmunoGen Ovarian, Fallopian tube, Endometrial, and has shown her true faith in the platform; Peritoneal the CEO joined the company in March 2015 from Takeda’s oncology unit, formerly known Phase II polatuzumab vedotin Roche/Seattle Genetics B-cell lymphoma, Non-Hodgkin’s lymphoma as Millenium Pharmaceuticals. “Three partnerships in two years is a Phase II anetumab ravtansine Bayer/ MorphoSys/ImmunoGen Solid tumors, Mesothelioma testament to the fact that we are making real Phase II lifastuzumab vedotin Roche/ Seattle Genetics Ovarian, Fallopian tube progress,” said Protopapas, who noted that the Phase II TAK-264 Seattle Genetics/ Oesophageal, Pancreatic lead program, XMT-1522, “is very robust.” She Takeda Pharmaceuticals pointed out that Mersana’s ADCs can attach Phase II depatuxizumab mafodotin AbbVie (Abbott)/Seattle Genetics Brain, NSCLC, Head and neck, Colorectal 15 drugs to the antibody, instead of the typical four seen in other ADCs. Phase II vadastuximab talirine Seattle Genetics Acute Myelogenous leukemia ADCs have been evolving over the last Phase II rovalpituzumab tesirine Stem CentRx Small cell lung cancer several years and are becoming of increased Phase II BMS-986148 Bristol-Myers Squibb Co. Solid tumors interest to many companies. ADCs are made up of a cytotoxic payload attached with a Source: Citeline Pharmaprojects

14 February 12th 2016 @scripnews scripintelligence.com © Informa UK Ltd 2016 headline news Pierre Fabre To Feed R&D Pipeline France’s Pierre Fabre has set up an innovation equity if that makes sense, but we are not But he also pointed out that what fund to invest in collaborations with start- looking to sit on company boards,” he added. differentiates the fund from VCs is the ups and biotech that is very much tailored Pierre Fabre Pharmaceuticals is undergoing company’s laboratory resources and its to the “needs of a mid-sized European a re-engineering of its R&D effort that has clinicians and researchers. And although “we pharmaceutical company,” the company included the closing of research facilities and are not going to necessarily compete with big announced Feb. 3. job losses, and the fund will be used to build pharma in terms of numbers, we are going to The Pierre Fabre Fund for Innovation, whose up its pipeline in three core areas of oncology, market significant firepower in terms of being size was undisclosed, is a strategic initiative to dermatology and onco-dermatology, where it able to mix cash and human resources and build relationships and to use the company’s has marketed products or research expertise. offer an attractive value proposition to our research laboratories and know-how in Currently, Pierre Fabre’s pharma pipeline external collaborators.” collaborations with biotechs and public and is thinly populated, although it does have Audoly also believed the dynamics of private research laboratories, in order to bring some early clinical-stage CNS products and investing and collaborating with European disruptive medicines to patients, said Laurent consumer products in development, and biotechs was to some extent different to Audoly, head of research and development at recently added to its oncology portfolio, by collaborating with US biotechs. “We are only Pierre Fabre Pharmaceuticals. “We will share licensing Array BioPharma’s investigational an hour away by plane from most of the value and risk with external collaborators and MEK inhibitor binimetinib and its BRAF innovation hubs in Europe, and can work a lot will exit collaborations when they no longer inhibitor encorafenib for marketing in Europe closer with our partners,” he noted. make sense,” Audoly added in an interview and merging markets. The products are Pierre Fabre is due to start roadshows with Scrip. nearing completion of Phase III studies. in Europe shortly to explain its ideas, “Our objective is to get a drug on the Audoly is agnostic about how the fund and has set up a steering committee market in the next five years using this would interact with venture capital. “We are consisting of Bertrand Parmentier, general mechanism, and we are going to be looking to create momentum, and we do manager of Pierre Fabre laboratories, transparent and have skin in the game,” Audoly not mind collaborating with corporate VC, Frédéric Duchesnes, general manager of continued. “A collaboration might mean standard VCs, or syndicates of investors,” he Pierre Fabre Pharmaceutical’s division, and getting proof of concept or early clinical data said. “We are going to uncover a lot of great Frédéric Desdouits, executive vice president that could trigger an option deal or licensing projects in Europe. At the same time, we will of licensing and acquisitions. Audoly will agreement, and we might take a minority not exclude any other geographical corridors.” manage the project. [email protected]

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© Informa UK Ltd 2016 @scripnews scripintelligence.com February 12th 2016 15 headline news Zika Gets Political It’s inevitable that whenever an issue of Lawmakers demanding concern among Americans reaches a fever answers and pointing fingers pitch – and generally not before – lawmakers are quick to demand answers, often pointing fingers of blame. And it’s been no different for the Zika virus, which has been spreading through Central and South America since first being detected in Brazil this past May – found now in nearly 25 countries and the US territories of Puerto Rico and the US Virgin Islands, with dozens of cases reported in the US of Americans who traveled to affected countries acquiring the virus. The International Health Regulations Emergency Committee of the World Health

Organization (WHO) is mulling over at a Feb. Pan JJ/shutterstock.com 1 meeting whether the outbreak constitutes a “public health emergency of international concern.” And US officials last week said there’s already efforts underway by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, in developing two vaccine candidates to prevent Zika, with several In a letter to Fauci, Sen. Kirsten Gillibrand “The feds should deploy all the possible biopharmaceutical companies expressing (D-NY) urged him to shift the agency’s resources to prevent contain and treat the interest in taking those products through to resources to “aggressively combat this global Zika virus abroad,” Schumer said during a Jan. advanced development. health challenge” and “prioritize” research into 31 briefing with reporters. The US government the Zika virus. also needs to “expeditiously work with private Gillibrand said she would plead with her industry to develop a vaccine a treatment and Lawmakers say not enough is colleagues on the Senate Appropriations a test for the virus,” he said. being done to protect the public Committee to provide the NIAID with Sen. Edward Markey (D-MA) also sent letters emergency funding to support its efforts in to health and human services secretary Sylvia and insist the response should accelerating the development of screening, Mathews Burwell and WHO director-general treatment and prevention technologies. Margaret Chan asking each to explain what have started sooner She also went on to lecture Fauci – one efforts they had underway to deal with the of the world’s preeminent experts on Zika virus. Sen. Lamar Alexander (R-TN), chair of infectious diseases – on how Zika is spread, In their letters, all of the lawmakers the Senate Health, Education, Labor and which may have brought a few eye rolls expressed their concerns about the growing Pensions (HELP) Committee, on Jan. 29 said from the NIAID chief. evidence there may be links between Zika he plans to “soon” convene a hearing to “gain Fauci wasn’t the only top government and microcephaly, which causes abnormally a better understanding of how the Congress health official to get harangued by lawmakers small heads and brains in babies. can support efforts to prevent further over the Zika virus. ‘It is critical that we better understand spread of the virus and protect families Indeed, Centers for Disease Control and the nature of the link between the virus and from being affected” – calling the situation Prevention director Thomas Frieden – also microcephaly, as well as other potential negative “heartbreaking,” a “big concern” and a “threat” a highly regarded expert in infectious pregnancy and public health outcomes,” Sen. to the US. diseases – also got a few letters from Patty Murray (D-WA), ranking member on the But several US lawmakers have complained lawmakers telling the agency what’s what Senate HELP Committee, told Burwell. not enough is being done to protect the about Zika, including one jointly from Sens. Sen. Richard Blumenthal (D-CT) didn’t public and insisted the response should have Ron Johnson (R-WI), chair of the Senate waste any time with the agency chiefs and started sooner – noting that NIAID director Homeland Security and Governmental Affairs instead went to the top – calling on President Anthony Fauci had acknowledged his Committee, and Tom Carper (D-DE), the Barack Obama to ask Congress for funding in agency has “not spent anything” previously ranking member, and a separate letter from his fiscal year 2017 budget request to combat on R&D activities for diagnostics, vaccines or Chuck Schumer (D-NY). the Zika. therapeutics on Zika, although he did point “The Zika virus has left tragedy in its wake, But Obama already directed Burwell, Fauci, out the US has made “substantial resource and while I appreciate that federal agencies Frieden and others on the president’s national commitment to the virus class,” spending are beginning to focus on the emerging security and health teams to step up their $97m on research in other flavivirus areas, like threat of the virus, more must be done,” efforts to fight Zika. West Nile virus and dengue fever. Johnson said in a statement. [email protected]

16 February 12th 2016 @scripnews scripintelligence.com © Informa UK Ltd 2016 R&D bites R&D Bites show any efficacy in slowing decline in the 6-minute ZIKV Vaccine Candidates walk distance (6MWD) compared with placebo. The Lilly drug was tested in a Phase III study in 330 Speed Into Labs patients with DMD, a devastating disease that effects When Scrip first wrote about Zika virus (ZIKV)

Titov Nikolai/shutterstock.com mostly young boys and results in declining muscle less than two weeks ago there was no record function. These boys don’t usually live into their of any clinical development ongoing for a teenage years and often die of problems with lung treatment or vaccine against the mosquito- function after living much of their life in a wheelchair. transmitted disease, let alone any available therapies. There was just one collaborative Lilly’s Cyramza Indian Debut? pair working preclinically on a possible DNA- Eli Lilly & Co. appears to be on course to bringing based vaccine, Inovio Pharmaceuticals and its anticancer, Cyramza (ramucirumab), to India, after a key local expert panel recommended the GeneOne Life Sciences, but this was a recently under FDA scrutiny, with a filing from the Cranbury product for marketing in two indications. A subject launched program at the very early stages site in the US. Top Sun officials anticipate savings expert committee (SEC), which advises the Indian of research. But as we enter, at least seven around 30% for the US healthcare system with the regulator on trial-related permissions as part of potential ZIKV vaccine programs are now generic’s arrival. a layered approval process, has recommended in play from various groups, including big marketing authorization for ramucirumab for pharma, biotech and government research UK’s Mission Banks £60m gastric cancer and non-small cell lung cancer bodies and there are still more on the horizon. For DUB Inhibitors (NSCLC). Lilly told Scrip that it was awaiting the It would be fair to say that public interest in UK fund manager Neil Woodford’s investment trust formal letter from the SEC, but shared no specifics ZIKV and its potential link to birth defects, the has joined existing investors in a £60m fundraising on its India plans for Cyramza. India currently World Health Organization’s recent forecast by Mission Therapeutics, the UK drug discovery firm follows a three-tier review process for clinical trials, working to discover drugs targeting the ubiquitin under which applications are initially evaluated by to expect 3-4 million infections across the pathway. The company was set up in 2011 by the specialized SECs. The recommendations of the SECs Americas in the next 12 months, and perhaps management team of kuDOS Pharmaceuticals, are vetted by a technical review committee and the upcoming Olympic Games in Brazil, at the which was bought in 2005 by AstraZeneca after finally cleared by an “apex committee.” epicenter of the outbreak, have helped to spur it had conducted early development of the now scientific research for vaccine development. approved ovarian cancer drug Lynparza (olaparib), India’s Bharat Enters Zika Fray With an inhibitor of poly ADP ribose polymerase (PARP). Two Vaccine Candidates Mylan Generics In Europe Mission’s scientific founder and chief scientific India’s Bharat Biotech International Ltd. has Mylan’s generic versions of zonisamide capsules, officer is Professor Steve Jackson, who founded announced what it called two “promising” amlodipine-valsartan tablets and rasagiline tablets KuDOS and who continues to carry out pioneering potential vaccine candidates to protect against received positive opinions from the EU’s top research into DNA damage repair at Cambridge the mosquito-borne Zika virus which has been scientific advisory panel on Jan. 28, but the US University’s Gurdon Institute. declared an international public health emergency company withdrew a marketing application for and said it was seeking global patents for generic aripiprazole earlier in the month because of Gilead Files Truvada For HIV PrEP the vaccines. The privately held firm said in a formulation issues, the European Medicines Agency The European Medicines Agency has accepted statement it believed it was “probably” the first reported Jan. 29. The three products cleared Gilead Sciences’ filing for the use of its HIV drug company in the world to seek a global patent for marketing are generic versions respectively Truvada in pre-exposure prophylaxis (PrEP), a new for a vaccine against the virus, which has been of Eisai’s epilepsy therapy Zonegran, Novartis’s indication that AIDS activists and others have been tentatively linked to a steep rise in babies in antihypertensive Exforge (amlodipine plus valsartan) urging Gilead to seek in the EU for some time. South America born with microcephaly, a serious and Teva’s Parkinson’s disease therapy Azilect. The news comes after the French government condition characterized by a small head and brain. Several other companies already have approvals for last month began reimbursing Truvada for PrEP The virus also is suspected of causing a rare illness generic versions of rasagiline in the UK, and other under a “temporary use recommendation” (RTU), known as Guillain-Barre syndrome that can lead to companies may have EU approvals for generic a regulatory tool that is used to make marketed temporary paralysis. zonisamide or amlodipine-valsartan through drugs available for a non-authorized indication. national or decentralized procedures. Gilead said at the end of last year that it planned Amgen’s Repatha Meets Endpoints In to file a centralized approval application with the GAUSS-3 Trial US Cost-Saver Gleevec Generic EMA in the first quarter of 2016. Truvada, which Results from Amgen’s Phase III GAUSS-3 trial Sun Pharma has launched its generic version of contains emtricitabine and disoproxil fumarate, evaluating Repatha (evolocumab) in patients Novartis’ blockbuster anticancer Gleevec (imatinib was approved in 2005 for use in combination with with high cholesterol have added to the growing mesylate) in the US at a savings of around 30%, other antiretroviral agents for the treatment of evidence that the novel drug has the ability to putting the spotlight on the specialty segment HIV infection in adults, and according to Gilead reduce LDL (low-density lipoprotein) cholesterol which is probably, for the first time, witnessing it is “currently the most prescribed antiretroviral in those patients who cannot tolerate statins or genericization of such a high cost therapy. Manish treatment in Europe.” decrease levels of this ‘bad’ cholesterol through Jain, a founder partner of SageOne Investment diet. The three-part GAUSS-3 (Goal Achievement Advisors, told Scrip that he expected Sun to rake DMD Community Hit Again After Utilizing an Anti-PCSK9 Antibody in Statin in sales of around $450m on a “conservative basis” With Cialis Fail Intolerant Subjects-3) study, evaluating the from its generic Gleevec during the exclusivity The hopes of patients with Duchenne muscular injectable proprotein convertase subtilisin/ period at current price levels, ruling out the need dystrophy hit another roadblock last week as the kexin type 9 (PCSK9) inhibitor, met its co-primary to go any lower for now. The Indian firm, being the patient group received news that Eli Lily & Co.’s endpoints, top-line data show. The two endpoints first-to-file an ANDA for generic Gleevec with a para tadalafil was not effective in treating the devastating were the mean of percent reductions from IV certification, is eligible for 180 days’ marketing pediatric disease. Parent Project Muscular Dystrophy baseline in LDL cholesterol seen at weeks 22 and exclusivity. Sun had earlier de-risked its Gleevec published a letter from Lilly on Feb. 3 that expressed 24; and the percent reduction from baseline in generic, originally filed from the Halol site, currently the company’s disappointment that tadalafil did not LDL-C at week 24.

© Informa UK Ltd 2016 @scripnews scripintelligence.com February 12th 2016 17 headline news

NewLink Brings Witty’s Wish: Hold Off On GSK Flavivirus ‘Dream Break-Up Chatter There is an “extraordinarily low” likelihood let’s just put together these two massive Team’ To Zika of GlaxoSmithKline Plc. spinning off its companies…on Monday. Then on Tuesday NewLink Genetics Corp. is not just another consumer healthcare business within the let’s do something completely different company jumping on the bandwagon of next three years, said CEO Andrew Witty. with them. The reality is there is a huge the latest global health crisis – in this case, Getting the margin structure right of the amount of day-to-day activity if we want the Zika virus, a mosquito-borne illness joint venture with Novartis was a “three year to secure the sales growth and the margin rapidly spreading throughout Central and journey” and despite making “great progress” development that we’ve laid out and South America and certain US territories, in 2015, there was still work to be done. committed to for this business.” with the first continental US transmission “Time is everybody’s friend here,” said Witty, Meanwhile, Witty is not ruling out further of the disease reported on Feb. 2, which speaking during the presentation of GSK’s augmentation of its portfolio. He cited the apparently involved sexual contact. annual results and fourth quarter financials recent addition of Bristol-Myers Squibb’s Indeed, the Ames, Iowa-based biotech, on Feb. 3rd. pipeline of HIV assets to ViiV Healthcare and an which recently gained worldwide Witty is also cautious of making the split expansion of GSK’s alliance with Adaptimmune recognition for its experimental Ebola after the three year timeframe, preferring to for cell therapies to treat cancer. vaccine – which so far has shown to be build “a balanced set of businesses” rather The BMS HIV transaction was a “competitive the most effective among those that have than aiming for one key vertical. “Things situation,” he said. It wouldn’t take a “rocket been tested in the past year – comes to are always changing, the markets always scientist” to work out who the competitors Zika with one of the most experienced fluctuate,” he said. “In the long run there were, and GSK was “able to go in and win” and knowledgeable vaccine development will always be evolution…with different those assets. teams working in flaviviruses. pressures [emerging].” “Actions speak louder than words, right? “I’ve got what I call a flavivirus dream A company with a “character of So very clearly, we have got capacity,” said team,” declared Thomas Monath, chief innovation” married with “annuity” Witty. However, “We’re not going to be sucker scientific officer and chief operating officer businesses such as GSK’s vaccines and punched into buying an asset that’s 20% at NewLink’s infectious disease division. consumer health units “is very valuable.” cheaper than an extraordinarily overpriced In Monath’s past life, he was the chief GSK took a lot of flak in and around [asset] two months ago. And we’ve all seen science officer at Acambis Inc., a publicly 2013 as growth was in significant decline. that happen.” traded company that was acquired in “And this was because we had a massive Any acquisition would have to fit within 2006 by Sanofi-Pasteur, the vaccines pharmaceutical business that had reached GSK’s current portfolio. “We have an awful division of Paris-based Sanofi SA. maturity,” he said. Had GSK been a pure lot of innovation in-house coming through. While at Acambis, Monath led the play pharma, pulling itself out of that We have an awful lot of collaboration assets development of the ChimeriVax flavivirus decline would have been a major coming through. So I’m not sat here starving platform on which Sanofi’s now-successful undertaking. Instead, it was able to boost or desperate... [However] where we see things dengue vaccine, Dengvaxia, was based. its vaccine and consumer healthcare units, that fit really well, we’re going do it.” Dengvaxia is the only approved dengue resulting in £2bn of new product sales in GSK’s R&D portfolio has a number of vaccine in the world – winning regulatory 2015, of which $682m was in the fourth significant milestones coming up in the nods this past December in Mexico, The quarter, noted Witty. 2016/2017 timeframe. These include up Philippines and Brazil. At the halfway point in 2015, GSK said it to 10 regulatory filings, including Shingrix Monath said the ChimeriVax flavivirus expected to deliver new product sales in (shingles vaccine), sirukumab (rheumatoid platform – which he called “my baby” excess of £6bn by 2020. Witty now believes arthritis), Benlysta SC (lupus) and ICS/LABA/ – also was used to make vaccines GSK will likely hit the £6bn mark in 2018. LAMA (COPD). against Japanese encephalitis and West Revenues are now split across It also has up to 10 Phase III starts Nile, although the latter is only used in Pharmaceuticals 58%, Consumer Healthcare scheduled including cabotegravir (HIV), animals, with the world still waiting for a 26% and Vaccines 16%. Pharmaceuticals daprodustat (anemia) and the Men ABCWY product for humans. turnover was £14.2bn in 2015, down 7% vaccine, plus up to 20 Phase ll starts in Sanofi itself on Feb. 2 announced it, on a reported basis, primarily reflecting the immuno-inflammation, oncology, respiratory too, was launching a Zika vaccine project disposal of GSK’s late stage oncology business and infectious diseases. based on its dengue platform – declaring to Novartis. GSK has been working hard to transition that its “expertise and established R&D and Witty did acknowledge that it would its respiratory portfolio away from Advair to industrial infrastructure” for Dengvaxia could “disingenuous” to dismiss the “optionality” of a new generation of products. While Witty be “rapidly leveraged to help understand splitting up the company, but noted there knows he can’t rule out the possibility of a the spread” of the Zika virus “and potentially would be a “whole series of challenges” generic Advair in the US in 2017, “I’m not speed identification of a vaccine candidate including the “not insignificant matter” of its spending every waking moment worrying for further clinical development.” partner Novartis in the joint venture, that about it,” he said. “It’ll be a bump in the road Monath said he brought along would make such a move “challenging.” [if it comes],” but GSK has restructured in a “number” of his Acambis/Sanofi Also, and “more importantly,” according anticipation of a generic Advair and “it would teammates to work with him at NewLink. to Witty, was the issue of maintaining be coming into a much less strategically Read the full story online at: “the momentum and performance” of important phase of the company.” http://bit.ly/1ol4TnX [email protected] the company. “Sometimes people think [email protected]

18 February 12th 2016 @scripnews scripintelligence.com © Informa UK Ltd 2016 “THe Pink sHeeT” & scriP inTelligence Marketing SolutionS

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Matt Dias • HeaD of aDvertising Phone: +44 (0) 20 701 74188 Email: [email protected] “The Pink Sheet” expert view French Industry Head Lauds New Drug Pricing Deal After years of a rather frosty relationship with for hepatitis C, which “took the government market,” Lamoureux said. “This is interesting the French drug pricing authorities, it seems by surprise,” he said. “These major innovations because as well as assessing the budgetary things are improving, at least if the agreement were not well anticipated, and we think that impact we will be able to gauge the savings just inked by the industry association Leem is having more predictability means a more generated and we hope to better get an idea anything to go by. coherent economic policy.” of the role of medicines in the efficiency of The latest three-year framework agreement Under the new agreement, companies the healthcare system.” (“accord cadre”) signed by Leem and the have committed, as far as possible, to provide government’s pricing committee CEPS data needed to anticipate the arrival of Performance Contracts (Comité Economique des Produits de Santé) “therapeutic innovations likely to have a “Performance contracts,” which are used seems to be based on a more consensual significant budget impact for payers or a where a price cannot be agreed under the approach to the question of balancing access significant impact on the organization of usual mechanisms, are another key aspect of to new medicines with the need to keep healthcare in the coming five years.” the new deal. While these figured in previous healthcare spending within reasonable limits. As for clarity, Lamoureux said that the framework agreements, not much use was According to Leem’s director general negotiators wanted to remove all the made of them, according to Lamoureux. “But Philippe Lamoureux, the deal is evidence ambiguities that plagued the previous now the new agreement gives more detail of a new pragmatism on the part of the agreement. For example, for a number of on how these agreements should work. They authorities, and is the result of “dialogue years Leem had had disagreements with the will also be applied when setting the prices of and concertation.” The agreement that has authorities over the amount of savings that orphan drugs, which was not the case before.” been reached, he says, is “both balanced and needed to be made in the pharma sector. Under performance contracts a conditional modern, because each side has listened to the “But now we are working together on trends price is established and a set of parameters laid other’s concerns as well as trying to anticipate in spending, savings from cost-containment out to evaluate the drug’s performance in the the therapeutic revolutions of tomorrow.” measures, and so on.” real-life setting. The assessment can be done The agreement, Lamoureux told Scrip in an But possibly the most important aspect of in various ways, such as using observational interview, contains fewer ambiguities than the deal is its consensual, two-way nature. “In studies, market data, or information from its predecessors, offers more predictability in our dialogue with the government,” Lamoureux registries. The result can be a re-evaluation of terms of the prices of costly new drugs, and said, “we said the agreement needed to the price or the payment of rebates. gives more weight to “performance contracts” prioritize the bilateral aspect, so that when we As before, the agreement also has an based on real-life results. have difficulties we will try to find a solution accelerated pricing procedure for some And while providing for better recognition within the contractual framework, not through innovative drugs, and a “pre-evaluation” of innovation, it allows more scope for taking authoritarian measures.” system whereby products that have gained account of efforts to promote the use of The fact that the government is more a marketing authorization recommendation generics and biosimilars and the way that willing to listen was demonstrated by the fact from the European Medicines Agency’s medicines are prescribed and used in practice. that the 2016 social security financing law CHMP can be submitted to the CEPS and The framework agreement, which is passed at the end of last year “has not added the transparency committee (which assesses renegotiated every three years, lays down any new constraining measures, as was the the medical value of drugs) before they have principles for setting new drug prices, mainly case in the three earlier laws. For France, this is gained a full MA, thereby reducing the time to on the basis of medico-economic evaluations a real revolution.” a pricing and reimbursement decision. There carried out by the HTA body, the HAS (Haute The 30-page framework agreement is a are also clearer rules for decisions on products Autorité de Santé). These principles then complex document, with a great deal of such as drug-device combinations. form the basis of individual companies’ emphasis on the practical arrangements for negotiations over their own pricing negotiating drug prices. Lamoureux singled Steering Committee agreements with the CEPS. out a few of aspects as deserving particular In order to oversee the proper implementation These individual agreements include a list attention. of the framework agreement, a steering of the prices of the company’s reimbursed One is the so-called “European guarantee” committee (Comité de Pilotage de la Politique products and any clauses attached to them which says that medicines of higher therapeutic Conventionelle, or CPPC) is being put in place. (such as triggers for any price revision), as well value will have a price that is not lower than The CPPC, composed of representatives of as any commitments in terms of promotion the lowest price in four reference countries – the pharma industry and the CEPS, will aim to and proper use of medicines. Germany, Italy, Spain and the UK. This guarantee ensure that the principles of the agreement are is valid for five years, and can be extended to properly applied, and that it works as it should. Predictable And Clear six years for products for which studies have It will also act as a forum for discussions on In its discussions with the government over been carried out in accordance with a pediatric monitoring drug spending, both current and the framework agreement, Leem emphasized investigation plan (PIP). Lamoureux said that predicted, and any changes in price setting three key principles, Lamoureux said: Leem managed to fend off government efforts and regulation, and will propose measures that predictability, clarity, and the bilateral nature to exempt from this guarantee those products could have a favourable impact on the financial of the agreement. with the highest budgetary impact. regulation of healthcare systems. That there was a real need for predictability Playing a bigger part now is medico- The CPPC will set up a working group to – for example, in terms of keeping an eye economic evaluation. “We decided with look at proposals for new ways of financing on the kinds of new products that might be the government to develop studies on the new innovative drugs, and in addition will heading the health insurers’ way – was clearly budget impact for all products with sales of have three “technical groups”. demonstrated by the arrival of the new drugs more than €50m in their second year on the [email protected]

20 February 12th 2016 @scripnews scripintelligence.com © Informa UK Ltd 2016 stockwatch Courage Under Fire One of the most frightening experiences I had as an infantry soldier was to come under, albeit simulated, mortar fire. Sitting in a damp ditch at night whilst the enemy threw what would have been high explosive and shrapnel at me gave me nightmares for weeks afterwards. In a very metaphorical sense, this is what the stock market for life science stocks feels like at the moment. Gojda/shutterstock.com Lukas Almost every day the pharmaceutical and biotechnology indices trade down in a barrage of selling, and bad or even mediocre news from this earnings season inflicts severe damage. The effects over the past year of foreign currency translations on companies reporting in either US dollars or Swiss francs continue to take their toll both on results for results the analysts from JP Morgan and Piper tax rate. The analysts from JP Morgan noted last year, and on financial outlooks for 2016. Jaffray described as ‘impressive’ and ‘very that while its 2016 EPS guidance was below Pfizer Inc. kicked off another week of strong’, respectively. Gilead beat consensus both consensus estimates and the $4.20 fourth-quarter earnings announcements estimates of sales and earnings by significant management incentive target, AstraZeneca’s with sales and earnings that beat analysts’ margins and while there was some discussion remuneration committee (who owe their jobs consensus estimates, although the earnings on the strength of the ex-US sales of its HCV to the management’s over-optimistic targets per share (EPS) beat was a modest $0.01. As antivirals against weakness in the US, the which enabled Pfizer’s bid to be rebuffed) if to set the cautious tone for the week – and worst criticism that appeared to be levelled at would probably ensure that its management with more than half of its sales outside the Gilead was – like that of Pfizer and most other continue to receive their bonuses. Talk about US – Pfizer warned of a currency headwind of profitable life science companies to have “you scratch my back.” Interestingly, the about $2.3bn for 2016. Not for the first time, reported so far – around weak 2016 guidance. prospect of pariah status seemed to fit with the devaluation of the Venezuelan Bolivar Pfizer has already answered last quarter’s AstraZeneca CEO Pascal Soriot’s laissez faire was responsible in Pfizer’s case, this time questions on what it was going to buy, while dress code as he appeared tie-less at the delivering a dent of about $800m to its 2016 Gilead addressed those questions this quarter analysts’ meeting on the same day as Martin sales guidance. The analysts from Citigroup with the short-term fix of an expanded $20bn Shkreli appeared as the only similarly attired described Pfizer’s fourth quarter as ‘largely buy-back of its own shares. The Gilead share testifier before a Congressional Oversight robust’ but highlighted the lower quarterly price ended the week up 3.0%. committee. AstraZeneca’s shares finished the tax rate, which would have provided some The middle of last week was bracketed week down over 7.2%. respite from the effects of weak currencies. As by the fourth-quarter earnings reports of No infantry soldier comes out of a mortar long as its results don’t deviate too far from the UK’s biggest pharmaceutical companies, barrage unscathed. The best you can hope analysts’ estimates, Pfizer is likely to get a free GlaxoSmithKline Plc (GSK) and AstraZeneca for is to be covered in mud. Some, like pass over the next year as the merger with Plc. GSK delivered results that the analysts AstraZeneca, will take a direct hit. Allergan Plc completes. On the other hand, from Citigroup described as ‘startlingly close The Magna Biopharma Income fund the merger and integration of two companies to consensus expectations’ and concluded holdings include Pfizer, Allergan, Gilead, as big as Pfizer and Allergan are likely to result that ‘the organic GSK thesis is not exciting.’ Novartis, Abbott and AbbVie. in a bit of a corporate “building site” at least GSK has become a focus of interest, like Andy Smith into 2017 and that lack of visibility in this Johnson & Johnson (J&J) and possibly market is unlikely to endear investors who Novartis AG, in the potential break-up of Andy Smith is chief investment officer of Mann shun opacity. The analogy of the building their conglomerate structures. Whilst the Bioinvest. Mann Bioinvest is the investment site is quite germane to the Pfizer-Allergan management of all three companies are adviser for the Magna BioPharma Income transaction since with the Allergan share price resisting investor pressure to do what Pfizer fund which has no position in the stocks trading at about a 20% discount to Pfizer’s has promised to consider after the Allergan mentioned, unless stated above. Dr Smith gives offer, investors may be thinking that planning transaction, they would do well to look at an investment fund manager’s view on public permission may be denied. The prospect of how the quarterly results of Baxter Inc. and life science companies. He has been lead fund further executive action by the US Treasury Abbott Inc. continue to benefit from share manager for four life science– specific funds, Department hangs whistling over this sales of their former spin-outs of Baxalta Inc. including International Biotechnology Trust and transaction like an inbound mortar. However, and AbbVie Inc., respectively, and Abbott’s the AXA Framlington Biotech Fund, and was the recent public and political outcry against large holding in Mylan Plc. Shares of GSK awarded the Technology Fund Manager of the the president’s justified executive action on finished the week down 1.6%. year for 2007. US gun laws may have done this particular AstraZeneca reported fourth-quarter inversion an unintended favour. The Pfizer sales that were 1% ahead of (declining) share price ended the week down 4.2%. consensus estimates, and Core EPS that For all Stockwatch articles visit Perhaps the savior of the sector came in the was 2% below. Like Pfizer, AstraZeneca’s scripintelligence.com/stockwatch form of Gilead Sciences Inc., which unveiled earnings quality was reduced by a lower

© Informa UK Ltd 2016 @scripnews scripintelligence.com February 12th 2016 21 pipeline watch

Scrip’s weekly Pipeline Watch tabulates the most recently reported late-stage clinical trial and regulatory developments from the more than 10,000 drug candidates currently under active research worldwide.

Late-stage clinical developments for the week 29 January-4 February 2016 Lead Company Partner Company Drug Indication Market Comments REGULATORY APPROVAL Dr. Reddy’s – Zembrace SymTouch migraine US The FDA has approved ZEMBRACESymTouch a drug-device combination product Laboratories (sumatriptan succinate) intended for the treatment of acute migraine episodes, with or without aura, in injection adults who are inadequately managed with existing treatment regimens. The a prefilled, ready-to-use, single-dose disposable autoinjector containing 3 mg of sumatriptan, will be marketed in the US by Promius Pharma. Otsuka Holdings OptiNose Onzetra Xsail (sumatriptan migraine US OptiNose’s licensing partner, Avanir Pharmaceuticals, has reported that the FDA Co. Ltd. nasal powder), formerly has approved Onzetra Xsail , for the acute treatment of migraine with or without AVP-825 aura in adults. It is the first product developed by OptiNose to receive FDA approval and is an intranasal medication delivery system using the novel Xsail Breath Powered Delivery Device, and is expected to be available in the US in coming months. AstraZeneca PLC – Tagrisso (AZD9291, non-small cell lung cancer EU Conditional marketing authorisation for the treatment of adult patients with osimertinib) 80mg once- (NSCLC) locally advanced or metastatic epidermal growth factor receptor (EGFR) T790M daily tablets mutation-positive NSCLC. REGULATORY FILING ACCEPTED Gilead Sciences – Truvada (emtricitabine HIV prevention EU Gilead Sciences’ Type II variation application for once-daily Truvada in Inc. 200mg/tenofovir disoproxil combination with safer sex practices to reduce the risk of sexually acquired HIV-1 fumarate 300mg) infection among uninfected adults at high risk, a strategy known as pre-exposure prophylaxis or PrEP, has been fully validated and is now under evaluation by the EMA. Truvada was approved by the EMA in 2005 in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults. FAST-TRACK STATUS Conatus – emricasan non-alcoholic US For the treatment of liver cirrhosis caused by nonalcoholic steatohepatitis. Pharmaceuticals steatohepatitis Inc. Eagle – Ryanodex (dantrolene neurology US For the treatment of exertional heat stroke, an investigational new indication for Pharmaceuticals, sodium for injectable the product. Eagle plans to meet with the FDA to review the results of the clinical Inc. suspension) trial and to determine next steps for this development program. BREAKTHROUGH THERAPY DESIGNATION Allergan plc – Rapastinel (GLYX-13) major depressive disorder US Allergan announced that its Phase III-ready investigational medication rapastine (MDD) received Breakthrough Therapy designation for adjunctive treatment of MDD. This follows the Fast Track Designation for rapastinel granted by the FDA in 2014. CHMP POSITIVE OPINION ON FIRST APPROVAL Actelion Nippon Shinyaku Uptravi (selexipag) pulmonary arterial EU For the long-term treatment of PAH in adult patients with WHO functional class Pharmaceuticals hypertension (PAH) (FC) II-III, either as combination therapy in patients insufficiently controlled with Ltd. an endothelin receptor antagonist and/or a phosphodiesterase type 5 inhibitor, or as monotherapy in patients who are not candidates for these therapies. Bio Products – Coagadex 250 IU and 500 Factor X (Stuart-Prower EU For the treatment and prophylaxis of bleeding episodes and for perioperative Laboratory Ltd. IU powder and solvent for Factor) deficiency management in patients with hereditary Factor X deficiency. Coagadex was solution for injection. designated as an orphan medicinal product on September 2007. Bristol-Myers AbbVie Empliciti (elotuzumab) multiple myeloma EU For the treatment of multiple myeloma as combination therapy with Revlimid Squibb Company and dexamethasone in patients who have received at least one prior therapy. CHMP POSITIVE OPINION ON SUPPLEMENTAL APPROVAL Otsuka Holdings Lundbeck Abilify Maintena schizophrenia EU The CHMP adopted a positive opinion for a Type-II variation related to the update Co. Ltd. (aripiprazole) of the European summary of the product characteristics for Abilify Maintena to include data related to its effect and safety on acutely relapsed adults with schizophrenia. Abilify Maintena is indicated for maintenance treatment of schizophrenia in adult patients stabilized with oral aripiprazole and the new data will support the physician in transitioning patients to the prolonged release formulation after symptom control has been achieved. Celgene – Revlimid (lenalidomide) mantle cell lymphoma EU The CHMP adopted a new indication as follows: “Revlimid is indicated for the Corporation treatment of adult patients with relapsed or refractory mantle cell lymphoma.” Novartis AG Ligand Promacta (eltrombopag immune EU The CHMP adopted an extension to the existing indication as follows: Revolade is olamine) thrombocytopenic indicated for adult chronic immune (idiopathic) thrombocytopenic purpura purpura patients aged 1 year and above who are refractory to other treatments (e.g. corticosteroids, immunoglobulins)

22 February 12th 2016 @scripnews scripintelligence.com © Informa UK Ltd 2016 appointments

COMPLETE RESPONSE LETTER Telesta – MCNA bladder cancer US The FDA has issued a Complete Response Letter to Telestas BLA for MCNA. In this Therapeutics Inc. letter, the FDA communicated that an additional Phase III clinical trial for MCNA would be necessary to adequately establish MCNA’s efficacy and safety. The FDA also encouraged Telesta to meet with them to discuss further clinical development of MCNA. REGULATORY FILING Synergy Ironwood plecanatide chronic idiopathic US The plecanatide NDA is supported by positive results from two Phase III clinical Pharmaceuticals constipation trials which Synergy completed in 2015. If approved, Synergy plans to launch Inc. plecanatide with the this indication in the 1Q 2017. SUPPLEMENTAL REGULATORY FILING GlaxoSmithKline – FluLaval Quadrivalent seasonal influenza US This vaccine is currently approved for active immunisation against influenza A plc (influenza vaccine) vaccines subtype viruses and type B viruses, in persons three years of age and older. The submission seeks an expanded indication for children six months through 35 months of age. Eli Lilly & Boehringer Ingelheim Basaglar (biosimilar insulin types 1 and 2 diabetes US Eli Lilly has submitted a supplemental application for an 80-unit Basaglar pen for Company glargine) FDA review. Boehringer Eli Lilly Jardiance (empagliflozin) type 2 diabetes EU Eli Lilly announced that they submitted data from the EMPA-REG OUTCOME trial Ingelheim GmbH of cardiovascular outcomes associated with Jardiance to European regulators. PHASE III TRIAL INITIATION Spectrum Hanmi Pharmaceutical eflapegrastim (SPI-2012) neutropenia / leukopenia – Spectrum Pharmaceuticals has initiated the planned ADVANCE trial to evaluate Pharmaceuticals the safety and efficacy of SPI-2012 as a treatment for chemotherapy-induced Inc. neutropenia in patients with breast cancer, which will serve as the basis for a BLA filing. The company expects to complete enrollment in 2017. Roche Holding AG AC Immune crenezumab Alzheimer’s disease – A Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel- group, efficacy and safety study of crenezumab in patients with prodromal to mild Alzheimer’s disease is currently recruiting participants. Target enrollment is 750 participants. PRODUCT LAUNCH Boehringer Pfizer Spiriva (tiotropium asthma US Boehringer Ingelheim Pharmaceuticals announced that Spiriva Respimat is now Ingelheim GmbH bromide) available by prescription for the treatment of asthma in US pharmacies. Eagle – docetaxel injection breast, gastric, head and US Eagle Pharmaceuticals announced the shipment and commercial availability of Pharmaceuticals neck, prostate and non- Alcohol-Free Docetaxel Injection for the treatment of breast cancer, non-small cell Inc. small cell lung cancer lung cancer, prostate cancer, gastric adenocarcinoma, and head and neck cancer. Docetaxel Injection is the first alcohol-free formulation approved in the US. Amgen Inc. - Blincyto (blinatumomab) acute lymphocytic US Amgen announced that the Company launched Blincyto, for the treatment of leukemia acute lymphocytic leukemia. Nippon Shinyaku - Erizas Nasal Powder 200µg allergic rhinitis South Nippon Shinyaku announced that their licensee YooYoung Pharmaceutical has Co. Ltd. 70 metered spray Korea launched, in South Korea, a dry powder spray for allergic rhinitis, Erizas Nasal (dexamethasone Powder 200µg 70 metered spray, a product developed for South Korean market. cipecilate) Source: BioMedTracker

Immune Pharmaceuticals, Inc. has appointed started his career at Schering-Plough in 1992 as a Sickle cell disease focused Dilaforette, AB. has John Neczesny to its board of directors; he sales representative. appointed Lena Jendberg vice president of will sit on the the audit committee and on development. Jendberg joins the company from the compensation committee. With 27 years’ Patheon has appointed Andrew G. Long senior Swedish Orphan Biovitrum AB (Sobi), where she experience in investment banking, Neczesny has vice president and global business controller. He was global program director, project and portfolio previously been managing director at Oberon brings over 25 years’ experience to the company management and strategic operations since 2010. Securities, LLC. and vice president, corporate and most recently was vice president, global finance development at Par Pharmaceuticals Companies. of biotech product development company, Fisher CellCentric, a company developing anti-cancer He was also an investment banker at Bear Stearns & Scientific Group for Thermo Fisher. Prior to this, Long compounds, has appointed Nigel Brooks Co. Inc., in the Healthcare group, and later held the was vice president, worldwide finance and supply director of translational science and Martin Page position of managing director. chain management at Cambrex Corporation. consultant. Brooks was previously involved in AstraZeneca plc’s clinical trials and he also led the Astellas Pharma Inc. has promoted James Agios, a company focused on cancer and rare AstraZeneca urology disease area team. He currently Robinson from president, Astellas Pharma US to genetic metabolic disorders, has appointed holds a senior leadership role at the Manchester president Americans Operations, for Astellas US Steve Hoerter to the newly created position of Cancer Research Centre. Page brings experience in LLC – effective April 1, 2016. Robinson, who joined chief commercial officer – effective Feb. 16, 2016. oncology R&D and held various senior management the company in 2005 as vice president of health Hoerter, who brings more than 20 years’ experience positions including European oncology therapeutic systems and was named senior vice president of to the company, joins Agios from Clovis Oncology area head for Glaxo-Wellcome, and global head sales and marketing in 2011, will succeed Masao Inc. where he was CMO. He has also held senior of oncology research for Johnson & Johnson Yoshida, who is retiring in June 2016. Robinson commercial roles at Genentech and Roche. Pharmaceuticals where he was vice president.

© Informa UK Ltd 2016 @scripnews scripintelligence.com February 12th 2016 23 There’s a reason why some of the world’s LARGEST Life Sciences companies are growing their businesses IN WALES

And you could too.

No-one delivers like Wales. Wales is a thriving place for life sciences companies to grow and prosper. With access to world-leading researchers, highly skilled graduates and science professionals, it is no wonder global industry leaders have chosen to grow their business on Welsh soil. GE Healthcare, OrthoClinical Diagnostics, Siemens Healthcare, Zimmer Biomet UK and ReNeuron all have a presence here. Wales has key strengths in med-tech, pharma services, e-health and cell therapy, and growth is accelerating in the sector due to our vibrant eco-system. The heart of this is our Life Sciences Hub – set up to stimulate collaboration and innovation between Business, Academia, the NHS and Government organisations. The dedicated £100m Life Sciences Investment fund can also provide equity funding to businesses and as a result, in Wales, ReNeuron is developing one of the UK’s most advanced commercial cell therapy manufacturing facilities. With success stories such as this, it is no surprise Wales is building a reputation as a world class centre of excellence in Life Sciences.

To join the growing number of life sciences companies thriving in Wales, JustAsk.Wales.com +44 (0) 3000 6 03000

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