Pharma Ceos Tackle a Tough Question: for Good Real Estate on Formularies

Winter Is Coming: What Can Novo BMS’ Mike Burgess Talks Challenges Stockwatch Nordisk Do Next After Stock Fall? and Developments In 2017 Drug failures in Phase III and value- Recent stock tumble and struggles What should we expect from BMS based pricing were two forces affecting have revealed armored Novo’s soft outside of oncology in 2017? (p16) Horizon and Vertex last week (p21) underbelly (p4)

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Scripscrip.pharmamedtechbi.com Pharma intelligence | informa year. That’s a very efficient way of increasing profits without innovation.” No one else was quick to agree with that suggestion, however. Pfizer’s Read responded, “I totally disagree with that.” He said the cost of drugs system-wide has not changed in two decades. “Whether you talk about three prices a year, two prices a year, double-digits, the cost of drugs has not changed,” he insisted. Lilly’s Ricks pointed to his company’s experience with insulin, which has come under attack from the public because of increasing cost. “Our net pricing hasn’t changed in seven years. It’s gone down slightly,” he said. “Our net is flat to declining.” But, he added, “The patient hasn’t seen any of that.” The reason is because pharma com- Shutterstock: Jirsak Shutterstock: panies often increase the wholesale list cost of drugs, then return money to payers in the form of rebates and discounts in exchange Pharma CEOs Tackle A Tough Question: for good real estate on formularies. Milligan, who as a top executive at Gilead has experienced his share of public criticism ‘Why Don’t People Like You?’ over the $1,000-per-pill price of the hepatitis JESSICA MERRILL [email protected] C treatment Sovaldi, talked about the need to work with payers and how that relation- Pfizer CEO Ian Read, Regeneron CEO & Co. incoming CEO David Ricks and Astellas ship contributes to the overall problem. Leonard Schleifer, Gilead CEO John Milli- Pharma Inc. president-Astellas Americas Jim One of the biggest issues with the price of gan and Lilly’s incoming CEO David Ricks Robinson were asked by Forbes editor Mat- Sovaldi was the substantial bolus of patients discussed pharma’s reputation problem thew Herper to answer a tough question at waiting to receive treatment, which pushed during the Forbes Healthcare Summit. the Forbes Healthcare Summit in New York a lot of people into the system at the same Dec. 1: “Why don’t people like you?” time, posing a unique challenge to insurers. panel of A-list pharmaceutical in- Regeneron’s Schleifer was the one that “We were unable to have a good enough dustry CEOs tried to boil down why answered the question the most directly. conversation with the payers” about Gil- Ait is that an industry that develops “The real reason we aren’t liked, in my view, ead’s HCV drugs, Milligan said. “Perhaps we life-improving medicines has a bad reputa- is because we, as an industry, have used were a little conservative about what we tion in the eyes of the public – though they price increases to cover up the gaps in in- could or should have said to them to al- never really did agree on the answer. novation,” he said. low them to prepare for the number of pa- Pfizer Inc. CEO Ian Read, Regeneron Phar- “I may be kicked off the all-star team,” tients that came forward.” As part of recent maceuticals Inc. CEO Leonard Schleifer, Gil- Schleifer joked, “But it’s just a fact. The price discussions on off-label communication, ead Sciences Inc. CEO John Milligan, Eli Lilly of drugs has gone up double digits twice a CONTINUED ON PAGE 7

BROUGHT TO YOU BY THE EDITORS OF PHARMASIA NEWS, START-UP AND SCRIP INTELLIGENCE IN THIS ISSUE Drug treatment for hearing loss

Gap between invoice, prices widening

5 Pfizer fined in UK 8 20

COVER / Pharma CEOs Tackle A Tough Question: from the editor ‘Why Don’t People Like You?’ [email protected] 3 Mylan CEO Takes Center Stage To Address EpiPen Pricing Scandal Even pharma CEOs can’t agree on the question of 4 Winter Is Coming: What Can Novo Nordisk Do Next drug pricing: Pfizer’s Ian Read and Eli Lilly’s David After Stock Fall? Ricks squared off against Regeneron’s Leonard Schei- fler on this topic at the Forbes Healthcare summit, 5 Decibel Therapeutics: Protect. Repair. Restore. where this season’s pharma villain Heather Bresch 6 New Global Generics Head At Teva also took the stage in defense of Mylan’s EpiPen price 6 Bullish Lilly Takes On New Alzheimer’s Candidate increases. In the UK, Pfizer and Flynn were fined for exploiting a loophole to hike the price of an off-pat- 7 Novartis’ Zykadia ASCEND-4 Study Close But ent epilepsy drug by up to 2,600%. No Cigar In NSCLC Most pharma companies declare they aim to serve 8 UK Fine For Pfizer/Flynn’s ‘Excessive And Unfair’ patients. Actions speak louder than words, though, Pricing Sends Clear Message To Others and the actions of those who adopt price inflation as 10 After Solanezumab, What’s Next? Alzheimer’s Options a business model simultaneously create pain for pa- Take The Stage At CTAD tients and tarnish the image of the industry. This is particularly galling for companies that eschew such 13 R&D Bites practices. It is also ironic that the generics sector, 12 Lilly’s Alzheimer’s EXPEDITION3 Proves Positive which should drive down prices on patent-expired For Biogen’s Anti-Amyloid At CTAD drugs, is responsible for some of the most controver- 14 Jardiance’s Label Expansion Will Change Diabetes sial price increases. Some of the blame can be shared Management with PBMs, insurers and the supply chain, but the fact remains that certain firms have exploited pricing 14 AbbVie/J&J’s Imbruvica On Track For GvHD confusion to practise pricing abuse, and ultimately 15 Sanofi Turns To Digital Transformation In Crisis-Hit that’s not good for patients or for pharma. China Vaccines Market 16 Interview: Bristol-Myers’ Mike Burgess Talks R&D Challenges, Portfolio Developments In 2017 17 Xencor To Raise $110m For IO Pipeline exclusive online content 18 Business Bulletin

VIDEO: Dimerix CEO Explains Company’s Different 19 Mylan Plans Workforce Reduction After M&A And Drug Combo R&D Strategy Price Scandal Global director of content for Informa Pharma Intelligence, Mike 20 Policy & Regulation Briefs Ward, talks to Kathy Harrison, CEO of Australian biotech Dimerix, about the company’s unusual business model. 21 Stockwatch: What Links Actimmune And Vertex’s http://bit.ly/2hljnlb Event Horizon?

AiCuris Seeks Partners For Antibacterial Programs 22 Pipeline Watch AiCuris CEO Holger Zimmermann talks to Mike Ward, global 23 Appointments director of content for Informa Pharma Intelligence, about the company’s journey to becoming a clinical biotech company since being spun out of Bayer AG as a small research group a decade ago. http://bit.ly/2gDx6oU @scripnews /scripintelligence

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2 | Scrip intelligence | 16 December 2016 © Informa UK Ltd 2016 HEADLINE NEWS

Mylan CEO Takes Center Stage To Address EpiPen Pricing Scandal CEO Heather Bresch defended her company’s controversial decision to raise the price of the allergy medicine to $600 during the Forbes Healthcare Summit and even took questions from fellow pharma insiders like “Why did you ruin it?” JESSICA MERRILL [email protected]

ylan NV CEO Heather Bresch, who The Forbes audience was notably a pricing scandals, like Mylan with EpiPen or became a central figure in the friendlier one than Bresch has confronted Turing Pharmaceuticals AG’s extravagant Mpublic drama that played out ear- in Washington, D.C., and some other ven- price hikes for Daraprim (pyrimethamine), lier this year over the EpiPen (epinephrine) ues, but participants still put pressure on which resulted in former CEO Martin Shkre- drug pricing scandal, continues to defend her to justify the company’s actions. One li being hit with fraud charges. the company’s decision to substantially raise audience member, pointing to some of the Most pharma executives have tried to the price of the life-saving allergy medicine good work Mylan has done providing af- paint those incidences as one-off examples and put some of the responsibility at other fordable HIV medicines to patients in Africa, of bad actors putting a negative spotlight players in the distribution chain. asked, “Why did you ruin it? What you did on the broader industry, though double- “We got a lot of things right [with was take all that good will and destroy it.” digit price increases on mature medicines EpiPen], but we got some things wrong,” Bresch responded, “We have spent $1bn annually or even more frequently are large- Bresch acknowledged to a room full of over the last eight years. That investment ly a standard practice across the industry. pharma insiders during the Forbes Health- was real and we believe it has produced Bresch insisted Mylan is not a bad actor. care Summit in New York City Dec. 1. What significant results.” “That is not who we are. We have a real op- the company failed to recognize as it raised portunity to show who Mylan is,” she said. the price of EpiPen from $100 in 2008 to ‘I do believe the system “We are not the company that bought a $600 in 2016 was how health insurance product, raised the price overnight and had changed and how that change would needs to be reinvented,’ our business model is not just taking old impact the ability of consumers to pay for Bresch said products and raising prices.” She pointed the medicine, she said. to the generic drugs Mylan is developing, “We did not fully appreciate the speed and the hundreds of millions of dollars the and the impact of patients in the high-de- company spends in R&D as evidence. ductible plans and the exposure that was Mylan didn’t develop EpiPen, but ac- She said Mylan now has the opportunity going to have,” Bresch said. quired the product from Merck & Co. Inc. to change the dialogue and work to help The chief executive’s defense of the pric- in 1997, which makes the enormous price solve some of the issues industry and pa- ing strategy has remained largely on point hike harder to justify. tients face when it comes to addressing since August, when the price of EpiPen But Bresch has insisted that Mylan in- drug pricing. became a big story in the mainstream me- vested heavily in improvements to the “I do believe the system needs to be re- dia and caught the attention of legislators. EpiPen delivery device and expanding ac- invented,” Bresch said. “If EpiPen had to be Mylan has tried to shift some of the blame cess to the drug, including to schools. to insurance companies, because of the “Headlines can get ahead of the facts,” the catalyst to show this window into what growing reliance on high-deductible health she said. “Today, we reach 80% more pa- families are facing in a rapid rise in high-de- plans that has indeed led more patients to tients than we did when we acquired ductible health plans and that can create feel the impact of drug costs, and also to EpiPen.” But expanding access to the prod- the change that the pharmaceutical pric- the broader drug supply chain, which ab- uct, including through legislation in some ing system needs to evolve in, it will have sorbs most of the impact of price increases. states requiring schools to stock EpiPen in been worth it.” For example, during an appearance be- the event of severe anaphylactic shock, has Drug pricing was a big theme at the Forbes fore the House Oversight and Government been a win-win for Mylan. Summit. During a separate discussion earlier Reform Committee hearing in September, “It has allowed for a reasonable profit,” in the day, Allergan PLC CEO Brent Saunders Bresch put the spotlight on pharmacy ben- Bresch admitted. But, she said Mylan has and Express Scripts Holding Co. Chief medi- efit managers and the lack of transparency in been misunderstood, pointing most no- cal officer Steve Miller also discussed drug drug pricing due to a complicated payment tably the company’s role in manufacturing pricing. Issues like rebates and transparency system that includes rebates, discounts and cheap generic drugs. “Today in the US, we and the challenges caused by high-deduct- allowances. In October, Mylan said it reached sell over 635 products at an average price ible health plans also came up, and Saunders an agreement with the Department of Jus- of $.25 a dose,” she said. “Access and af- warned industry that the drug pricing con- tice to pay $465m to settle charges related to fordability has been our mission.” Industry troversy is a populist issue that will likely per- rebates to Medicaid for EpiPen, though the players generally have sought to separate sist under a Trump administration. deal has not been finalized. themselves from those behind the biggest Published online 5 December 2016

scrip.pharmamedtechbi.com 16 December 2016 | Scrip intelligence | 3 HEADLINE NEWS

Winter Is Coming: What Can Novo Nordisk Do Next After Stock Fall? Change must be due for Danish diabetes giant Novo Nordisk as the firm continues to flounder in the US thanks to a tough pricing environment, increased competition for insulin products and supposed cultural differences between European and American management teams.

LUCIE ELLIS [email protected]

recent stock tumble and struggles within US operations have revealed Aarmored Novo Nordisk AS’s soft underbelly, prompting some to ask whether the Danish diabetes drug developer could be the target of keen big pharma peers that might be looking to acquire a valuable diabetes portfolio. If this question had been asked six months or a year ago, around the time of the Pfizer Inc/Allergan PLC potential $160bn mega merger, the answer would probably have been no. Novo Nordisk has always had an aura of being untouchable. A company protected by its deep roots in Denmark and the umbrella shield of the Novo Nordisk Foundation. But a lot can change in a year and Novo Nordisk has had a particularly turbulent one: the company has twice cut its long- term growth targets; its CEO, Lars Rebien Sørensen, pulled forward his retirement by two years and now a successor is poised to take the reins; and the business has slashed 1,000 jobs from its workforce – half of these $106.96bn. Sanofi has had an up and down they were always overvalued relative to job losses were recognized in Denmark year when it comes to its stock traded on their European peers. Much of that froth and most of the rest focused on the US. NYSE, but it has managed to pull itself up has rightly come out of the stock. Having And while the firm has some of the best- from the lows periodically. Novo Nordisk, fallen that far, investors would likely accept regarded diabetes therapies in the world, on the other hand, appears to be on a slip- an offer that helps them recover at least pulling in a huge share of this vast patient pery downwards slope. some of those losses.” population, its US business has continued The two major shields for Novo Nordisk However, an acquisition offer by a non- to miss targets. Does being a part of Den- of importance to Denmark and the back- Danish acquirer (with the possible excep- mark’s body and soul as one of the biggest ing of the Novo Foundation remain, but tion of the historically Swedish AstraZen- employers in the country (with 18,210 staff with such a dramatic value loss in the latter eca PLC) would run up against the same based in the region) and being affiliated half of 2016 the possibility of a buyout is type of protectionist lobby that Pfizer ran with the Novo Foundation matter when a more reasonable than ever before. Because into when it tried to buy AstraZeneca, the company has lost almost half of its market of the company’s high staff headcounts in source said. value over just four months? Denmark (a reason one analyst told Scrip it Novo Nordisk told Scrip in response Since August this year, Novo Nordisk’s has previously made the sale of Novo Nor- to questions about its performance this stock price has fallen significantly on the disk near impossible) a lot of retirement quarter that it does not comment on its New York Stock Exchange from $56 on Aug. hopes rest upon the company doing well share price. 2 to a low of $31.50 in November. Its mar- and generating profit. ket cap is now $86.2bn. Compare this with Also, investors are in a vulnerable posi- FALLING SHORT IN THE STATES its major European diabetes rival Sanofi, tion as 2016 ends, making a buyout offer One of the biggest issues for Novo Nordisk which has also faced the same crunches more palatable then in previous times of is its failings on the US market. A recent dis- on drug prices on the US diabetes market, growth. One market spectator told Scrip: cussion drew Scrip’s attention to concerns yet has managed to retain a market cap of “Novo has fallen a long way recently but that the management of Novo Nordisk’s US

4 | Scrip intelligence | 16 December 2016 © Informa UK Ltd 2016 HEADLINE NEWS

operation is facing a culture struggle be- However, during an Oct. 31 earnings tween the company’s “Danish ways” and the call in London, in which Sørensen did not Decibel strikingly different US market. take part, Jørgensen elaborated: “We can Therapeutics: Novo Nordisk rules the European diabe- improve our performance in the US by tes market but its major stumbling block looking at our commercial operations. We Protect. Repair. for the past few years has been transfer- can improve the collaboration between ring that leadership and success to North the sales force, the medical people and Restore. America. And not all of its issues can be marketing to make sure they are better fo- Emerging Company Profile: Decibel Thera- blamed on a tough pricing environment cused and better aligned by what we do in peutics, a Boston-based company focused on in the US. the market,” he said. developing therapies for hearing loss, started The top three members listed on Novo Still Jørgensen claimed the company’s adding its voice in an emerging development Nordisk US’s website under executive team US business was “doing very well.” He space in 2015, with the aim of becoming highlight the lack of fresh blood within said, “In the US we have a lower price “the premier hearing therapies company.” the company’s failing US operations. The point, but still we expect that we can company’s head of North American opera- take volume. I still think we have a strong tions is Jakob Riis, a Danish national who organic business.” has been with the company since 1996. Its During this second call Jørgensen senior vice president of national diabetes pushed aside the idea of Novo Nordisk be- sales and former VP of US national diabe- ing involved in a “large, transformational” tes sales, Andrew Ajello, has been with the M&A deal. But as pressure mounts for the firm for 15 years – though he does bring in- climax of 2016, we could see back-pedal- sights from a 10-year tenure at GlaxoSmith- ing in this area. Kline PLC. Finally, Lars Green, current senior Other options for the business, with a buy- Shepeleva Tatiana Shutterstock: VP of finance and operations, moved over out still considered tricky due to the com- With ongoing research and preclini- to the US team from positions in Denmark pany’s current ownership caveats, could in- cal candidates for hearing loss, Decibel in 2014, having joined Novo Nordisk under clude the sale of some specific assets. Novo is looking to secure a beneficial col- a graduate scheme in 1992. Nordisk’s management has expressed a de- laboration that will bump up its profile Novo Nordisk noted in its third-quarter sire to pursue R&D activities in other disease and give it the funding it needs to earnings call in September that “2017 indi- areas outside of its diabetes foundation. move forward. cates low single-digit growth in sales and These include areas such as obesity and kid- There are no therapies currently flat to low single-digit growth in operating ney disease. To progress pipeline programs available for hearing loss that protect or profit both measured in local currencies.” in these fields the company will need more restore hearing, Decibel Therapeutics’ The company has highlighted the US as capital and a bigger R&D budget. CEO Steven Holtzman told Scrip, de- its biggest concern for 2017 and the reason The company is in the weakest position scribing the area as a “white space.” The for its drop in growth expectations – result- it has held for many years and the next condition is currently managed using ing in a long-term growth forecast cut from quarter will be crucial for Novo Nordisk to medical devices like hearing aids and 15% to 5%. Furthermore, incoming CEO pull up its value, but 2017 will be vital for cochlear implants, but Decibel aims to Lars Fruergaard Jørgensen, who up until six new CEO Jørgensen to prove he’s a turn- change the standard of care by develop- months ago had not been mentioned as a around man. ing effective pharmaceuticals to help potential successor to Sørensen, did little protect, repair and restore hearing. to quell concerns about the company’s US NOVO RESPONDS TO While there are several therapeutic operations during Novo Nordisk’s 3Q 2016 US PRICING PRESSURES treatments in the pipeline for hear- earnings update. The call was Jørgensen’s When asked about the current tough pricing loss from other biotechs and one first since being revealed as the next man ing market in the US, Novo Nordisk cited a big pharma asset being developed by in charge and one observer told Scrip Jør- recent open letter by North American head Novartis AG. Holtzman is certain that gensen missed his moment to prove Novo Riis. In the letter Riis outlines three tenets the Decibel is different. Instead of just re- Nordisk had its US troubles in hand. company will focus on to help solve pricing gurgitating existing research like other Instead Jørgensen said on the Sept. 29 issues in the US: biotechs, Decibel has “an end-to-end earnings call that the company was un- • create more pricing predictability; discovery translation medicine capabil- happy with its US operations. In response • transform the drug pricing system; ity” in this area. “No one in the world to questions about the bigger picture for • reduce the burden of out-of-pocket has that full set of capability in hear- Novo Nordisk and the company’s future, costs to patients. ing and our approach is to put that he said: “To be honest I think we have to The pharma said it would continue to in place and be the premier hearing acknowledge that we are not fully satisfied talk about US pricing issues over the com- therapies company for the next several with our US operation.” He added that “sig- ing months, but it is calling for better col- decades,” he said. nificant restructuring” would be needed to laboration around the problem. regain strength and stability in the US. Published online 8 December 2016 [email protected], 8 Dec 2016 scrip.pharmamedtechbi.com 16 December 2016 | Scrip intelligence | 5 HEADLINE NEWS

New Global Generics Head At Teva Bullish Lilly SUKAINA VIRJI [email protected] Takes On New

Just months after Teva closed the knew both businesses so well was thought Alzheimer’s $40.5bn acquisition of Allergan Generics, to be a big benefit to the integration. The Candidate the company said the man expected to deal closed in September, cementing Teva lead the integration, Siggi Olafsson, will as the global generic drug leader with an 8% Undaunted by its recent disappointment step down and be succeeded by Dipankar market share. with solanezumab, Eli Lilly is adding Bhattacharjee. Bhattacharjee, who has served as presi- another clinical-stage Alzheimer’s disease dent and CEO of Teva Generics Europe since candidate to its portfolio through an April 2013, is not as well known to investors. expanded agreement with AstraZeneca. Olafsson will remain active at the company AstraZeneca PLC and Eli Lilly & Co. to ensure a smooth transition until the end have agreed to co-develop MEDI1814, of March 2017. Bhattacharjee will be based in an antibody selective for amyloid-beta the US. 42 (Aβ42), which is currently in Phase I “There will be no shortage of disappoint- trials as a potential disease-modifying ment among investors with the somewhat treatment for Alzheimer’s disease. The sudden, and surprising, news yesterday that product was discovered in AstraZen- Siggi Olafsson will be leaving Teva at the end eca’s Medimmune laboratories. of 1Q17,” Barclays analyst Douglas Tsao said The build-up of plaques in the brain in a Dec. 6 research note. containing the peptide amyloid-beta Olafsson’s intimate familiarity with the (Aβ) is one of the characteristics of AD. Actavis business would have helped a chal- MEDI1814 binds selectively to Aβ42, a lenging integration, he added, particularly form of Aβ which is particularly associ- serving as a bridge between the two legacy ated with the disease. Earlier research Dipankar Bhattacharjee management teams. suggests MEDI1814 dose-dependently Credit Suisse analyst Vamil Divan said in reduces levels of this peptide. Despite eva Pharmaceutical Industries Ltd. a Dec. 5 note that he had spoken with the the solanezumab failure in the EXPEDI- has appointed Dipankar Bhattacha- company, which said “after a challenging 2.5 TION3 study, experts say the data do T rjee as president and CEO of its years at Teva, and in particular the many chal- point to a role for amyloid in the disease. global generic medicines group, effective lenges seen in 2016, Olafsson decided it was “MEDI1814 has a unique mechanism immediately, and he will be tasked with an time to move on.” among antibodies in clinical develop- enormous job: overseeing the integration of Some investors, apparently, have been ment and could provide a distinct ap- Allergan PLC’s generic drug business. questioning the high price of the deal, both proach to treating Alzheimer’s disease,” The surprising news that the company’s analysts said. Mene Pangalos, executive vice presi- generic medicines head Sigurdur (Siggi) “To have Olafsson now leave Teva just a dent, IMED Biotech Unit and Business Olafsson will leave the company was an- few months after the deal closed, and while Development, AstraZeneca, said. nounced Dec. 5, just three months after the integration is in process, makes it more In February 2014, AstraZeneca started Teva closed on the $40.5bn acquisition of difficult for us to believe Teva will obtain as a multicenter Phase I trial of MEDI1814 Allergan’s generic drug business. much value from the deal as they have previ- in the US in people with mild to moder- Olafsson, along with CEO Erez Vigodman, ously stated publicly,” Divan added. ate Alzheimer’s disease. The study was were the architects behind that deal and Teva, meanwhile, is highlighting Bhat- designed to evaluate single and multiple Olafsson in particular was viewed by inves- tacharjee’s track record of improving rev- ascending doses of intravenously and tors as an important asset to extract value enues and profitability. He joined the com- subcutaneously delivered antibody. from the merger because of his substantial pany as general manager of Teva UK, prior to Outcomes included measures of safety, generic drug experience. He most notably which he served 15 years at Bausch + Lomb. pharmacokinetics, and immunogenicity ran the business that was briefly known as In conjunction with the latest announce- of the antibody, as well as pharmacody- Allergan generics but was previously Actavis ment, Teva reaffirmed its full-year 2016 out- namics of blood and CSF Aβ concen- and also Watson Pharmaceuticals. He had look, and said it now expects to provide its trations. The trial was also designed to worked at Watson, which acquired Actavis 2017 guidance in January 2017. correlate results with ApoE genotype. in 2012 and led the integration of those two Published online 6 December 2016 The trial was completed earlier this year. companies as president-global generics from AstraZeneca and Lilly first joined 2012 to 2014. CLICK hands in Alzheimer’s in 2014 to jointly Vigodman recruited Olaffson to Teva in Read full story at: develop and commercialize AZD3293 2014 to turn around the company’s slowing http://bit.ly/2hIvhVw in a deal worth up to $500m. generic drug business. The fact that Olaffson [email protected], 9 Dec 2016

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CONTINUED FROM COVER pharma industry, however, most certainly payers and manufacturers have pushed for predates recent changes to the country’s Novartis’ Zykadia more leeway in what they are able to dis- insurance system, including the Account- ASCEND-4 Study cuss in advance of approvals, to allow for able Care Act. better planning. Milligan suggested the dislike is partly Close But No because the business is hard to understand. “Why doesn’t the general public like us? Cigar In NSCLC Number one, what we do is complex and The presentation of the full data from it’s hard to explain to somebody,” he said. Novartis’ ASCEND-4 study of Zykadia “It’s shocking for an industry that saves lives, show decent efficacy in first-line NSCLC prolongs lives and improves quality of life but are unlikely to be enough to overcome that we don’t have a better message that… doctors’ caution over its tolerability profile, is easy to understand and appeals to the especially with rival Alecensa snapping at head and heart.” its heels. In the case of Gilead’s experience in hepa- Patients with anaplastic lymphoma titis C, Milligan said. “I think we should have kinase-positive (ALK+) advanced

Shutterstock: alice-photo Shutterstock: spent a lot more time talking about it pub- non-small cell lung cancer (NSCLC) licly. It’s a little bit difficult. You can get into treated first-line with Novartis’ Zyka- promotion-prior-to-approval problems, but PUTTING THE BLAME ON HIGH dia (ceritinib) showed a doubling we do have the ability to talk to certain areas DEDUCTIBLE PLANS of mean progression-free survival about this.” compared with those on standard Pfizer’s Read mainly shifted the blame for first-line chemotherapy, the full the industry’s reputation problem to insur- data from the ASCEND-4 study ance companies, pointing out that patients ‘You can’t have it both presented at the World Conference on average in the US pay substantially more on Lung Cancer in Vienna this week for drug costs, about 15%, than they do for ways,” Regeneron’s reveal. The median PFS with Zyka- hospital costs, about 3%. A modern scien- Schleifer said. “You can’t dia was 16.6 months, compared to tific pharmaceutical industry cannot exist 8.1 months in patients treated with without a good insurance system, Read said. say I set the drug at a fair standard first-line chemotherapy “What we have seen in the last five years is price and then have these with maintenance, equating to a a dramatic shift in cost to the consumer,” he 45% reduction in the risk of disease added. “That is one of the reasons we have egregious price increases’ progression (p<0.001). such a negative perception. The insurance “The patient response to treatment has changed, has shifted who is paying out is high and durable in the first-line of pocket.” setting,” said Bruno Strigini, CEO of The increase in high-deductible plans Novartis Oncology, adding that the has resulted in more consumers having Read said the industry needs to stop company was initiating discussions to front the cost of drugs out of pocket. A apologizing for the value it brings to soci- with regulatory authorities worldwide prime example of how this challenge for ety. Improving communication around the on the basis of the results. Novartis patients has fallen back on pharma com- value of a medicine is a common theme in released the top-line data in September. panies is what happened with Mylan NV’s pricing debates, as is the need for transpar- The data for the oral selective ALK emergency allergy treatment EpiPen over ency across the distribution chain. inhibitor compare well with those the summer. The $600 cost of the treat- But Regeneron’s Schleifer returned the seen for Pfizer’s multi-targeted tyros- ment hit patients in their wallet, resulting dialogue from value to price increases. “If ine kinase inhibitor Xalkori (crizotin- in public backlash, and eventually putting you have a drug and you price it on day ib), which inhibits ALK among other a spotlight on the substantial price hikes one and you think you are giving it value kinases, in its pivotal trial for this set- the company took on the product over and that drug hovers a two- three- four- ting. In the published PROFILE 1014 eight years of ownership. year period, have you delivered twice as Phase III study of crizotinib in first- During another panel at the Forbes much value for the same drug with no in- line use in ALK-positive NSCLC, the Healthcare Summit, Mylan CEO Heather novation? No, you haven’t.” median PFS was 10.9 months among Bresch defended her company’s decision “You can’t have it both ways,” Schleifer crizotinib patients, as compared with to raise the price of EpiPen, which was added. “You can’t say I set the drug at a fair 7.0 months for patients in the chemotherapy group (p<0.001). These data priced at $100 when it was acquired. She price and then have these egregious price were first reported in 2014 and formed also tried to put some of the blame for the increases. How am I giving more value by the basis of an expanded approval for EpiPen scandal on insurance companies doing that? What I am doing is covering up first-line use. and the rise of high-deductible plans. The a lack of innovation.” public’s generally negative view of the Published online 6 December 2016 [email protected], 7 Dec 2016 scrip.pharmamedtechbi.com 16 December 2016 | Scrip intelligence | 7 HEADLINE NEWS

UK Fine For Pfizer/Flynn’s ‘Excessive And Unfair’ Pricing Sends Clear Message To Others IAN SCHOFIELD [email protected]

The UK competition authority has fined Pfizer and Flynn Pharma duce their respective prices to levels that were “profitable” but not a total of £90m for charging “excessive and unfair” prices for “excessive and unfair.” phenytoin sodium capsules; Pfizer has said it will appeal. With an Philip Marsden, chair of the case decision group for the CMA’s earlier CMA decision to impose a hefty fine on GlaxoSmithKline investigation, said this was the highest fine the CMA had ever for its part in a pay-for-delay deal, companies should pay careful imposed and that it sent out “a clear message to the sector that consideration to any competition issues raised by their pricing we are determined to crack down on such behavior and to pro- strategies for marketed drugs. tect customers, including the NHS, and taxpayers from being exploited.” he decision by the UK Competition and Markets Authority to But Pfizer rejected the findings set out by the CMA, claiming that impose a fine of almost £90m ($113m) on Pfizer and Flynn its behavior in this matter “fully complies with established competi- T Pharma for charging “excessive and unfair” prices for the anti- tion law.” It plans to appeal the decision and to seek clarity on the epileptic drug, phenytoin sodium capsules, should serve as a warn- roles of the Department of Health and the CMA in terms of regulating to other companies that may be considering significant price ing the prices of pharmaceuticals in the UK. increases on marketed drugs. Gustaf Duhs, head of competition at law firm Stevens & Bolton It is also likely to set alarm bells ringing among the other firms LLP, said it was “rare for competition regulators to take action that are currently under investigation by the CMA for suspected against excessive prices, as it is often difficult to define when a anticompetitive behavior, particularly as this is the second major price becomes excessive. Unsurprisingly much has been made by the CMA of the very dramatic overnight price increases for the drug.” Another lawyer, Duncan Liddell of Ashurst, said the CMA had “clearly decided to make a point with a record UK fine,” noting that the authority has been under pressure to “increase its anti- trust enforcement output.” Amid the uncertainties presented by Brexit, he said, “there’s a clear message here that boards should be including competition law compliance in their priorities for 2017.”

PRICES UP TO 2,600% HIGHER The phenytoin sodium capsules case dates back more than four years, to September 2012. Before that, Pfizer manufactured and sold the drug as Epanutin, and its prices were regulated. But in Sep- tember that year, it sold the UK distribution rights to Flynn Pharma, which de-branded the drug, meaning that it was no longer subject to price regulation. Since September 2012, Pfizer has continued to manufacture phenytoin sodium capsules and has supplied them to Flynn Phar- ma at prices that were “significantly higher than those at which it Shutterstock: Sirichai Puangsuwan Sirichai Shutterstock: previously sold Epanutin in the UK – between 780% and 1,600% higher than Pfizer’s previous prices,” the CMA observed. infringement decision by the authority in the pharmaceutical sec- “Flynn Pharma then sells on the products to UK wholesalers tor this year: in February it fined GlaxoSmithKline PLC £37.6m for and pharmacies charging them prices which have been between striking deals to delay the launch of cheaper generics of its antide- 2,300% and 2,600% higher than those they had previously paid for pressant Seroxat (paroxetine). the drug.” Announcing its decision to fine Pfizer Inc. a record £84.2m and The CMA said that the amount the NHS was charged for 100 Flynn Pharma Ltd. £5.2m for breaching competition law, the CMA mg packs of the product “rocketed from £2.83 to £67.50, be- said the companies “deliberately exploited the opportunity offered fore reducing to £54.00 from May 2014. As a result of the price by de-branding to hike up the price for a drug which is relied upon increases, NHS expenditure on phenytoin sodium capsules in- by many thousands of patients.” creased from about £2m a year in 2012 to about £50m in 2013. This “extraordinary” price rise for phenytoin sodium capsules had The prices of the drug in the UK have also been many times cost the NHS and the taxpayer “tens of millions of pounds,” the au- higher than Pfizer’s prices for the same drug in any other Euro- thority said, noting that it had ordered the two companies to re- pean country.”

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Key factors in the CMA’s decision were the companies’ dominant The CMA Infringement Procedure position in their markets, and the fact that epilepsy patients cannot Once a potential issue has been identified, the CMA carries out an easily be switched from one product to another, perhaps cheaper initial consideration of issues and informal evidence gathering. drug because of the risk of losing control over their seizures. If a decision to open a formal investigation is taken, the next The authority found that both companies held a dominant posi- stage is formal information gathering powers: publishing the case tion in their respective markets for the manufacture and supply of opening notice, issuing written information requests, conducting phenytoin sodium capsules, and that each had “abused that domi- interviews, visiting and searching premises to obtain information, nant position by charging excessive and unfair prices.” and analyzing gathered evidence. It also pointed out that epilepsy patients who are already tak- If there is sufficient evidence of infringement, the CMA issues a ing phenytoin sodium capsules should not usually be switched to statement of objections, setting out its provisional findings, the other products, including another manufacturer’s version of the supporting evidence and the proposed action. product, because of the risk of losing seizure control, which can Parties have a right to reply and make written and oral representations. have “serious health consequences.” As a result, it said, the NHS “had A decision is then taken on whether or not there has been an infringe- no alternative to paying the increased prices for the drug.” ment, and a decision is issued: either no grounds for action, or an infringement decision and action (financial penalties and/or directions). “LOSS MAKING,” SAYS PFIZER Parties have a right to appeal to against the decision to the Compe- Pfizer said that phenytoin capsules had been a loss-making product tition Appeal Tribunal. and that the Flynn transaction “represented an opportunity to secure ongoing supply of an important medicine for patients with epilepsy, GENERICS TO BE SUBJECT TO PRICE REGULATION? while maintaining continuity of manufacture.” The question of generic pricing was of course a key aspect of the When Flynn launched its product, it set a price that was “be- CMA decision – particularly the fact that as a debranded (generic) tween 25 and 40% less than the price of the equivalent medicine product, phenytoin sodium capsules were no longer subject to price from another supplier to the NHS which had long been regulated, regulation. For unbranded products, the government says it relies on and appeared to be acceptable to, the Department of Health,” Pfiz- competition in the market to keep prices down, but that where there er continued. is no competition there have been “cases of large price increases.” “Against that background, Pfizer believes the CMA’s findings are To tackle this issue in the longer term, it recently introduced the wrong in fact and law and will be appealing all aspects of the deci- Health Service Medical Supplies (Costs) Bill, which among other sion.” It said the ruling also highlighted “real policy and legal issues things addresses the fact that if a company has a mixed portfolio of concerning the respective roles of both the Department of Health branded and generic medicines and has joined the Pharmaceutical and the CMA, in regulating the price of pharmaceutical products in Price Regulation Scheme, no statutory controls can be applied to the UK” and that it would “seek clarity on these issues as part of the its unbranded generic products. appeal process.” Under the bill, the secretary of state for health could require com- But the CMA was dismissive of Pfizer’s claim about the loss-mak- panies to reduce the price of an unbranded generic or impose oth- ing nature of the drug. It said it had calculated that, “according to er controls, even if the company was in the PPRS. The government Pfizer’s figures, all such losses would have been recovered within said it “intends to use this power to limit the price of unbranded ge- two months of the price rises.” neric medicines where competition in the market fails and compa- Indeed, there has been little love lost between the two during nies charge the NHS unreasonably high prices for these products.” the development of the case. In March this year the CMA fined The bill passed scrutiny by the House of Commons on Dec. 6 and Pfizer £10,000 for failing to provide it with certain information will now go to the House of Lords. within the specified time limits, describing this failure as “flagrant” and “intentional.” OTHER FIRMS UNDER INVESTIGATION Pfizer hit back, asserting that the CMA had been “inflexible” on a The Pfizer/Flynn decision will make uncomfortable reading for request for an extension of time to reply, and that given the com- companies already under the CMA spotlight. The authority is cur- pany’s “full and thorough responses and cooperation,” it was “exces- rently investigating four other cases concerning anticompetitive sive” to issue Pfizer with a fine. conduct, anticompetitive activity and anticompetitive agree- Duhs said that one of the most interesting features of the Pfizer/ ments – all opened this year – and alleged discounts, which began Flynn case was that the companies had been told to reduce their in December 2015. prices to levels that are “not excessive and unfair.” This, he said, was The names of the companies involved have not yet been di- likely to “give the NHS and any other parties that may have suffered vulged. The CMA does not generally publish the names of parties loss or damage the right to sue without having to prove that Pfizer under investigation until the later stages of an inquiry unless there and Flynn are liable.” Damages were likely to be any provable over- are exceptional circumstances, for example where the parties’ in- charge, Duhs said. volvement in the investigation is already in the public domain or is If an appeal against the decision did not succeed, Pfizer and Fly- subject to significant public speculation. The CMA will usually only nn would be faced with a difficult dilemma in setting prices going include parties’ names in the notice of investigation at a later stage forward, he added: a price that is too high might breach the CMA’s of an investigation, typically if a statement of objections is issued direction, but a low price could potentially increase the level of any (see box above). damages that need to be paid to third parties. Published online 7 December 2016 scrip.pharmamedtechbi.com 16 December 2016 | Scrip intelligence | 9 HEADLINE NEWS

After Solanezumab, What’s Next? Alzheimer’s Options Take The Stage At CTAD Lilly will make its first presentation of solanezumab data from the recently failed Phase III EXPEDITION3 study during the Clinical Trials in Alzheimer’s Disease meeting where researchers will discuss amyloid beta and other hypotheses in Alzheimer’s disease Dec. 8-10 in San Diego.

MANDY JACKSON [email protected]

ndustry executives and biopharmaceuti- that the antibody’s impact on amyloid may velopers in the past, including H. Lund- cal analysts are reluctant to say that the not be great enough to translate into a beck AS and Otsuka Pharmaceutical Co. Ifailure of Eli Lilly & Co.’s solanezumab in a clinical effect. Ltd., whose idalopirdine failed in the first third Phase III clinical trial is the end of the The Datamonitor analyst said it will be of two Phase III studies in October. Pfizer’s road for the amyloid-beta hypothesis in important to understand how early in the 5-HT6 antagonist PF-05212377 failed in a Alzheimer’s disease, so does that mean an- disease that amyloid should be targeted – Phase II study, but analyses of data that other company could effectively treat the perhaps even before a mild or moderate the big pharma presented in July noted memory-stealing affliction with a drug that Alzheimer’s diagnosis – or whether target- differences between the Pfizer and Axov- targets the menacing protein, or will other ing the protein tau may be more closely ant drugs and development programs approaches be required? correlated with slowing disease progres- that could result in a positive outcome The answer seems to be that multiple sion, providing a greater benefit in later for intepirdine. and combined approaches will be needed stages of Alzheimer’s. Axovant chief development officer Law- to slow the progression of Alzheimer’s and Despite those questions, Elsayed said rence Friedhoff said in an interview with manage its symptoms, and targeting the Phase I data for Biogen’s amyloid-target- Scrip that the company has done its best amyloid-beta protein that causes plaques ing biologic aducanumab have been en- to design and execute an efficient Phase to build up in the brains of Alzheimer’s pa- couraging, so far. There are “some mecha- III trial that mirrors the successful Phase IIb tients still could be of use in the disease. nistic differences between aducanumab study for intepirdine as an add-on to Pfizer Researchers from industry and academia and solanezumab that could suggest Inc.’s now-generic Aricept (donepezil) – a will discuss several options in develop- that the failure of one does not have to drug for which Friedhoff led the development during the Clinical Trials in Alzheim- apply to the other,” she said. “For example, ment as an R&D executive at Pfizer. Int- er’s Disease (CTAD) conference from Dec. 8 aducanumab is targeting beta-amyloid epirdine probably will be dosed on top of to 10 in San Diego. fibrils and oligomers, directly impacting existing symptom-treating therapies, if the Data from Lilly’s Phase III EXPEDITION3 beta-amyloid plaques … whereas solan- drug is approved, he noted. trial for solanezumab will be presented dur- ezumab is targeting soluble monomers Friedhoff said intepirdine also could be ing a late-breaker presentation on Dec. 8. of beta-amyloid and this approach may prescribed in combination with disease- Lilly made a big bet that its amyloid- be less effective in reducing the toxicity of modifying drugs – perhaps even amyloid- targeting monoclonal antibody could slow amyloid pathology.” targeting treatments – if a therapy that the cognitive effects of Alzheimer’s and im- An analysis of long-term data from slows or halts the progression of Alzheim- prove the ability for patients with mild to Biogen’s Phase I clinical trial will be pre- er’s ever makes it to the market. moderate forms of the disease to perform sented at the CTAD meeting, but data “We never looked upon the [amyloid- normal, daily tasks. It was not a major sur- from two ongoing Phase III studies for the targeting] antibodies as competitors,” he prise in late November, however, when the monoclonal antibody are not expected said. “It’s certainly unlikely that we’re go- company said solanezumab did not suc- until 2022. ing to discover the cure for Alzheimer’s ceed in EXPEDITION3, since the antibody and that you’re going to be able to take failed in two prior Phase III studies – just AMYLOID-TARGETING ISN’T this pill or combination of pills to make it like several other fallen amyloid-targeting THE ONLY OPTION go away. It will be like a lot of diseases of candidates. The next Alzheimer’s drug in line for po- old age where you take multiple medi- Datamonitor Healthcare analyst Maha El- tential US FDA approval does not target cations that change as you progress, like sayed said that “the failure of solanezumab the amyloid-beta protein that causes with high blood pressure, diabetes and does not necessarily have to mean that the plaques to build up in the brains of Al- heart disease.” amyloid hypothesis no longer holds true,” zheimer’s patients. Phase III data for Axov- Friedhoff said the Alzheimer’s research because it’s unclear how much of an im- ant Sciences Ltd.’s 5-HT6 antagonist int- and drug development field has reached pact the Lilly biologic has on modulating epirdine are expected in 2017, followed the conclusion that targeting amyloid amyloid levels in the brain. Pharmacoki- soon after by a new drug application alone is not the best path forward in treat- netic modeling has suggested that solane- (NDA) submission to the FDA, assuming ing the disease. zumab has limited central nervous system the study’s results are positive. Targeting Axovant recently acquired intellectual (CNS) penetration, Elsayed noted, meaning 5-HT6 has disappointed other drug de- property to make higher doses of cholines-

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terase inhibitors more tolerable. The company’s investors – and will present nine- “Our new insights are defining a more pany also has a 5HT-2A inverse receptor and 12-month safety results during the targeted, higher probability [of success] antagonist called nelotanserin that, like in- CTAD meeting. development path to advance promising tepirdine, is being tested in a Phase II study “We are very mindful of our resources, drug candidates,” Tolar said, by directing for Lewy body dementia. so we will do the best thing for the asset,” the right drugs to the right patients at the “These are modest steps, but when you Missling said in regard to next steps for right stage of their disease. add these modest steps together you can Anavex’s lead drug candidate. It’s possi- Alzheon will present data during the turn a disease that can be rapidly fatal into ble that Anavex will launch a mid- or late- CTAD meeting from a Journal of the one that can be managed effectively for stage trial in Rett syndrome, Parkinson’s Prevention of Alzheimer’s Disease pub- many years,” Friedhoff said. “If you can slow disease or another indication in 2017 to lication about the effect of tramiprosate progression by a third and another drug move the asset through development on people with the APOE4/4 genotype, can slow progression by a third and anoth- faster than it can in Alzheimer’s and at a which showed the highest efficacy sig- er one can too, you essentially have a cure.” lower cost. nal in the company’s Phase III studies in Patient enrollment in the Phase III MIND- “Other Alzheimer’s compounds do not North America and the EU, which failed SET clinical trial for intepirdine should be have that optionality,” Missling said. in 2007. completed by the end of 2016 and Axov- He noted that Alzheimer’s is a complex “This description of preferential effica- ant should be able to report the trial’s re- disease that may require multiple treat- cy of tramiprosate in APOE4/4 homozy- sults in late 2017. An NDA filing is expected ments, including combinations of novel gotes is the first for an amyloid-targeted by the end of next year. agents. Avanex 2-73 could be combined agent,” Tolar said. Tramiprosate and the Axovant will have two oral and two with a lot of its competition, given the oral follow-on drug ALZ-801, which is formu- poster presentations on Dec. 9 during drug’s tolerability to date and its efficacy in lated with increased bioavailability and the CTAD meeting showing data on drug the ongoing Phase IIa study. The company reduced gastrointestinal side effects, in- interactions between intepirdine and Al- already is testing Anavex 2-73 Plus, which teract with soluble beta amyloid peptide lergan PLC’s Namenda (memantine) in combines its drug with Aricept. monomers to prevent the formation of healthy subjects; placebo-controlled data “We are agnostic to the a-beta hypoth- amyloid plaques. on changes in how much patients de- esis,” Missling said. “We do believe it is toxic, An oral CTAD presentation on Dec. 9 pend on others for daily activities; results but it has to be looked at where it and will show that APOE4/4 genotype patients as an adjunct to donepezil (Aricept and what it’s doing. Some researchers say it is with mild Alzheimer’s disease had the best generics) in terms of functional efficacy; neuroprotective. We believe we are inde- response to tramiprosate in terms of cog- and Phase IIb efficacy results for the -in pendent of any hypothesis, because if it’s nitive and functional outcomes. A Dec. tepirdine/donepezil combo in patients overexpressed, it gets targeted; if not, it 8 poster presentation describes Phase Ib who completed the study. stays where it is.” clinical pharmacology data for ALZ-801. “We have completed a bridging Phase ONE DRUG TO EIMINATE A TARGETED TREATMENT I program with prodrug ALZ-801 includ- MULTIPLE TARGETS SEEKS NEW LIFE ing 163 subjects where ALZ-801 dem- Anavex Life Sciences Corp. is developing a Alzheon CEO Martin Tolar told Scrip that so- onstrated bioequivalence as well as an drug candidate for Alzheimer’s and other lanezumab’s failure strengthened “our belief improved safety and tolerability profile diseases that targets the sigma-1 and mus- that we must define Alzheimer’s popula- versus tramiprosate. The next step for carinic receptors to restore balance, or ho- tions based on a distinct biological pheno- the program is a Phase III [study] with meostasis, in cells. President and CEO Chris- type. This will enable us to develop medi- ALZ-801,” Tolar said. topher Missling told Scrip that its sigma 1 cines for Alzheimer’s using the successful Alzheon has designed a 400-patient receptor agonist turns the protein on, so cancer playbook of finding genetically-de- Phase III pivotal study for ALZ-801 based on that it attacks anything in cells that causes fined patients who overexpress the under- an end-of-Phase II meeting with the FDA an imbalance, whether that’s amyloid-beta, lying disease pathology and are uniquely to test the prodrug in patients with mild tau, inflammation or other causes. sensitive to a treatment.” Alzheimer’s disease who have the APOE4/4 genotype. “It’s a backup plan for restoring ho- The fact that multiple drugs have failed “Our target remains to start the study in meostasis if the day-to-day pathways of in Alzheimer’s disease is a key reason the second half of 2017 and we are com- homeostasis are not working as before,” why Alzheon is using a precision medi- pleting funding and partnership discussions Missling said. “It’s like a fire truck near a cine approach for the development of to advance the program,” Tolar said. house. If something happens, fire truck has ALZ-801. A planned Phase III program Published online 7 December 2016 to be there quickly. The protein is always in for the company’s prodrug of its own the endoplasmic reticulum and doesn’t act failed Alzheimer’s therapy tramiprosate unless there’s distress.” is focused on patients with the APOE4 Anavex has reported several updates genotype – a group of people with the CLICK View Other CTAD from the ongoing Phase IIa clinical trial highest risk of developing Alzheimer’s Presentations Of Interest for Anavex 2-73 in Alzheimer’s disease and who experience the earliest onset here: http://bit.ly/2gDk8Yu – with varying responses from the com- and fastest disease progression. scrip.pharmamedtechbi.com 16 December 2016 | Scrip intelligence | 11 HEADLINE NEWS

Lilly’s Alzheimer’s EXPEDITION3 Proves Positive For Biogen’s Anti-Amyloid At CTAD MANDY JACKSON [email protected]

Lilly’s Phase III EXPEDITION3 results for solanezumab at CTAD deposits in the brain as measured by PET imaging. Also, levels of contribute data to the Alzheimer’s field about the role of amyloid tau – another protein in the brains of Alzheimer’s patients that’s in disease progression, including the effect that other amyloid- associated with the disease – were higher in the solanezumab targeting antibodies may have in ongoing clinical trials, such as arm than in the placebo group, and brain atrophy was not sig- Biogen’s Phase III candidate aducanumab. nificantly reduced. However, Lilly consultant Paul Aisen, a University of Southern he presentation of Eli Lilly & Co.’s unsuccessful Phase III EX- California (USC) neurology professor and director of the Alzheim- PEDITION3 clinical trial for solanezumab was supposed to er’s Therapeutic Research Institute, said during a panel discussion T be the main event on the first day of the Clinical Trials in after Honig’s presentation that “this is not a refutation of the amy- Alzheimer’s Disease (CTAD) conference on Dec. 8 in San Diego, but loid hypothesis; it’s confirmation of the amyloid hypothesis,” calling updated results from the Phase Ib trial for Biogen’s earlier-stage am- EXPEDITION3 the best set of data to date that show a link between yloid-clearing antibody aducanumab stole the show after abstracts clearing amyloid from the brain and improving cognition and func- were leaked online. tion in Alzheimer’s patients. Lilly has committed to sharing its data from the company’s now The small reduction in soluble amyloid did result in a small dif- three failed Phase III studies for solanezumab and a company ex- ference in the Alzheimer’s Disease Assessment Scale-Cognition ecutive told Scrip that the EXPEDITION3 results, while disappoint- (ADAS-Cog) subscale for patients treated with solanezumab versus ing, will be illuminating for the Alzheimer’s research field. The study placebo – an 11% slowing in the rate of cognitive decline – but the of solanezumab in 2,129 patients with mild Alzheimer’s disease primary endpoint’s result was not statistically significant (p=0.095). already has shed some positive light on Biogen’s antibody, since Other secondary endpoint measures showed small, but sta- aducanumab had a greater effect on amyloid and generated dose- tistically significant differences between the two study groups – dependent responses in its ongoing Phase Ib study. Mini-Mental State Examination (MMSE; 13% slowing of cognitive Analysts provided hopeful responses to Lilly’s EXPEDITION3 re- decline; p=0.014), Clinical Dementia Rating-Sum of Boxes (CDR-SB; sults for solanezumab in terms of what they mean for Biogen’s adu- a 15% slowing in cognitive decline; p=0.004), and the Alzheimer’s canumab results, which showed a continuation of earlier responses Disease Cooperative Study-Instrumental Activities of Daily Living to the antibody, including some statistically significant data points, (ADSC-iADL; 14% slowing in functional decline; p=0.019). as well as a reduction in rates of amyloid-related imaging abnor- There are a lot of unanswered questions still about solanezumab, malities (ARIA) for patients treated with a new titrated dose. to be sure, but Honig noted that it is not clear whether the results Evercore ISI analyst John Scotti said in a Dec. 8 note that “solan- of EXPEDITION3 were attributable to the antibody therapy’s dose, ezumab did not produce statistically significant changes in amy- the study participants’ stage of Alzheimer’s disease or other factors. loid plaque deposition as measured by [positron imaging tomog- Aisen added that solanezumab may still have a role in Alzheim- raphy (PET)] compared to placebo. In fact, the absolute amount er’s for the right set of patients. Lilly is studying the antibody as of plaque that solanezumab removed in EXPEDITION3 was even a preventative therapy and in patients who have amyloid in their less … than what solanezumab had removed in prior post-hoc brains without cognitive impairment in addition to the ongoing analysis of select patients in prior Phase III trials where the results prodromal Alzheimer’s trial. were statistically significant.” Lilly senior vice president of clinical and product development SOLANEZUMAB BODES WELL FOR ADUCANUMAB Daniel Skovronsky said in an interview at the CTAD meeting that “[G]iven that solanezumab produced statistically significant results “it’s obvious that [EXPEDITION3] is a disappointment for patients on some secondary endpoints of cognition and function (most no- and for us.” However, he saw the final result as a positive develop- tably a p-value of 0.004 on CDR-SB, which is also Biogen’s primary ment for the Alzheimer’s field: “Across three trials, solanezumab is endpoint in ongoing Phase III trials), we believe these data 1) bode not working, but in each one we see a signal. It’s evidence that well for Biogen’s aducanumab in Phase III and 2) have minimal to amyloid does have a role,” Skovronsky said. “The future is a little no negative read across to the amyloid beta hypothesis (i.e., that re- brighter than if we hadn’t done this study at all.” moval of amyloid beta plaque likely results in clinical benefit, which Neurologist Lawrence Honig, Director of the Clinical Core of the Al- is being more robustly tested by aducanumab in Phase III,” Evercore zheimer’s Disease Research Center at Columbia University and a pro- ISI’s John Scotti wrote. fessor at the university’s medical school in New York City, presented Solanezumab targets soluble amyloid whereas Biogen’s adu- the EXPEDITION3 data during a special late-breaking session at CTAD. canumab clears the more bulky amyloid plaques, potentially leading Honig reviewed data that showed significant mean changes in to a more effective treatment, analysts surmised in their reviews of amyloid levels in plasma for solanezumab-treated patients, but Biogen’s leaked abstracts and a company statement that followed. that did not result in statistically significant reductions in amyloid Published online 9 December 2016

12 | Scrip intelligence | 16 December 2016 © Informa UK Ltd 2016 R&D BITES

Alexion’s Son of Soliris Aims To Takes Dosing Right Down Advantage For Synergy’s Plecanatide Alexion is setting its sights on eight- Over Rival Linzess Holds Up In IBS-C weekly dosing for its follow-up candidate to its blockbuster Soliris, testing Plecanatide met the primary endpoint in first Phase III trial in irritable this schedule in its new Phase III trial bowel syndrome with constipation, with less incidence of diarrhea than in patients with paroxysmal noctur- seen in Linzess trials. Synergy is awaiting approval in chronic idiopathic nal hemoglobinuria (PNH), based on constipation and appears on pace to file an sNDA in IBS-C during the first new Phase I/II data just presented at quarter. Top-line data for Synergy Pharmaceuticals Inc.’s plecanatide in ir- the ASH meeting in San Diego. Alex- ritable bowel syndrome with constipation (IBS-C) from the first of two piv- ion Pharmaceuticals Inc. has begun otal Phase III trials appears to be confirmation that the guanylyl cyclase C recruitment in a multinational study receptor agonist will have the advantage of less incidence of diarrhea than of ALXN1210, its longer- longer-act- its chief rival, Astellas Pharma Inc./Ironwood Pharmaceuticals Inc.’s Linz- ing antibody follow-up to its com- ess. There was also less incidence of diarrhea versus Linzess (linaclotide), also a GCC agonist, in the Phase III program for plecanatide in chronic plement C5 inhibitor Soliris (eculi- idiopathic constipation (CIC), its lead indication. Plecanatide is under re- zumab), in patients with paroxysmal view at FDA for CIC with an action date of Jan. 29. In CIC pivotal studies, nocturnal hemoglobinuria (PNH), plecanatide resulted in diarrhea as a side effect in 5.9% of patients receiving which it hopes will show the prod- the lower daily dose of 3 mg, and 5.5% of patients receiving the higher 6 mg uct can be effective given every eight daily dose, compared to the 16% incidence rate seen for Linzess in Phase III weeks, a significantly reduced dos- study. The rate of diarrhea in the first IBS-C Phase III trial was even lower ing burden compared with the older than in the Phase III trials in CIC – 3.2% in the 3 mg daily dose and 3.7% in product’s fortnightly schedule. With the 6 mg dose, according to the results Synergy released Dec. 9. Soliris, which was first launched in [email protected], 9 Dec 2016 2007, Alexion has successfully carved out a multi-blockbuster position through high prices, and proactively seeking new patients with the two rare to teach the immune system how dendritic cells that will attack the conditions for which Soliris is now to kill the cancer. After 17 years of cancer by teaching the immune sys- approved: PNH and hemolytic uremic work, Argos Therapeutics Inc. hopes tem what and where to attack. syndrome (in 2011). It is also being to present a breakthrough in 2017 [email protected], 9 Dec 2016 developed in other rare conditions in- with Phase III data for its lead can- volving complement inhibition. Alex- didate in metastatic renal cell carci- ion has recently diversified its portfo- noma – what CEO Jeff Abbey says will Gazyva’s GALLIUM Could lio with the approvals late last year of be precision immunotherapy that Be ‘Practice-Changing’ For two new products for other rare in- eventually could be applied broadly dications – Strensiq (asfotase alfa) for across the oncology space. During an Follicular Lymphoma hypophosphatasia and Kanuma (sebe- investor day presentation Dec. 7, the Genentech’s next-generation anti- lipase alfa) for lysosomal acid lipase Durham, N.C.-based biotech outlined CD20 antibody Gazyva bested the (LAL) deficiency – but sales for these the clinical development process for Roche subsidiary’s original CD20- are still tiny in comparison to Soliris. AGS-003 (now called rocapuldencel- targeting therapy Rituxan in first- [email protected], 8 Dec 2016 T) and talked about its plans for line follicular lymphoma – a result in commercializing and manufacturing the Phase III GALLIUM study that the drug. The company’s technol- one oncologist viewed as “practice- Argos Nears Phase III ogy stems from its Arcelis platform, changing.”Data from Genentech Inc.’s Results For Precision Cancer which can capture both mutated and 1,202-patient Phase III GALLIUM clini- Immunotherapy variant antigens from a specific pa- cal trial in previously untreated follicu- tient’s disease and produce an indi- lar lymphoma showed a 34% reduction With pivotal data expected in 2017 vidualized therapy for that patient. in the risk of disease progression or in metastatic kidney cancer, Argos Bringing the immunotherapy and death for the Roche subsidiary’s Gazy- hopes its drug will bridge the hot personalized medicine processes to- va (obinutuzumab) compared with the points of immuno-oncology and per- gether, Argos’ lead candidate is an company’s own Rituxan (rituximab) – a sonalized medicine with a drug that autologous therapy derived from ex- result that investigators view as poten- extract’s RNA from a patient’s tu- tracting the RNA from the patient’s tially practice-changing. mor and primes the dendritic cells tumor and optimizing it to produce [email protected], 5 Dec 2016 scrip.pharmamedtechbi.com 16 December 2016 | Scrip intelligence | 13 HEADLINE NEWS

Jardiance’s Label Expansion Will AbbVie/J&J’s Imbruvica On Change Diabetes Management Track For GvHD KEVIN SHANNON [email protected] Results suggest 67% objective response US approval of the first cardiovascular la- ments in early lines of therapy, after met- rate in second-line+ chronic graft versus bel expansion for an anti-diabetic medi- formin. Metformin is likely so ingrained in host disease; Phase III study is already cine will mark a shift in disease manage- physicians prescribing habits that it won’t testing Imbruvica for new onset disease. ment, says Datamonitor Healthcare lose much market share; instead, physi- Johnson & Johnson/AbbVie Inc.’s analyst Kevin Shannon. cians are more likely to add an SGLT-2 in- ambitious expansion plans for hibitor earlier. Jardiance’s label expansion the blockbuster BTK inhibitor Imbruvica got a leg up with promis- he US FDA approved the first car- is unlikely to have a major effect on GLP- ing updated data from a Phase I/ diovascular (CV) label expansion for 1 agonists or insulin, as they are primarily II trial of graft-versus-host disease an anti-diabetic, Jardiance (empa- used at different lines of therapy and don’t T presented in a late-breaker session at gliflozin; Boehringer Ingelheim GMBH/Eli Lilly compete directly with SGLT-2 inhibitors. the American Society of Hematology & Co.), on December 2, 2016. The drug is now Interestingly, physicians did not report a meeting Dec. 5. approved to “reduce the risk of cardiovascular specific patient population in which they After allogenic stem cell and death in adult patients with type 2 diabetes expected to see increased use of SGLT-2 bone marrow transplants, donor mellitus and cardiovascular disease”. inhibitors, despite a lack of reduction in non-fatal myocardial infarction and non- cells may attack the body, causing fatal stroke observed in the EMPA-REG GVHD, which can develop into a clinical results. chronic condition. High-dose steroid The FDA’s decision to allow Jardiance’s therapy is commonly used but is label expansion did not come as a sur- very toxic and lacks durability, and prise, but was certainly a relief for Lily and options are very limited after steroid Boehringer after the close advisory com- therapy fails. mittee vote. Imbruvica received breakthrough The decision was based on results from therapy designation with FDA for chronic GVHD, after failure with one Shutterstock: Lightspring Shutterstock: Jardiance’s EMPA-REG cardiovascular outcomes trial (CVOT) and a 12-11 vote in favor or more systemic therapies, in June and the company is expected to file Jardiance’s CV benefit and the result- of the label addition by the Endocrinologic for approval in the first half of next ing label addition are expected drive and Metabolic Drugs Advisory Committee year. significant uptake of the drug in the dia- on June 28, 2016. In December, the partners started a betes market. The split vote is not expected to in- Phase III frontline study of the drug in Respondents in a recent physician sur- hibit the drug’s uptake, though this may 186 patients with new onset moderate vey conducted by Datamonitor Healthcare change if results from Invokana’s (cana- or severe GVHD. The primary comple- and Biomedtracker on CV outcomes in gliflozin; Johnson & Johnson/Mitsubishi tion rate for the trial is March 2020, type 2 diabetes reported that the percent- Tanabe Pharma Corp./Daiichi Sankyo Co. according to clinicaltrials.gov. age of their type 2 diabetes patients who Ltd.) CVOT, expected in 2017, do not show The latest data presented at ASH receive SGLT-2 inhibitors will rise from 14% a CV benefit. earlier this month, show an objective to 25% (an 80% increase) over the next Jardiance’s label expansion is a significant step towards meeting a major unmet response rate of 67.2%, with re- three years. They expect this increase to be sponses in 71% lasting for at least five driven primarily by Jardiance, owing to its need in type 2 diabetes treatment. Car- diovascular complications are the lead- months, AbbVie reported, and about label addition and the data from the EMPA- one-third had complete responses. REG trial. ing co-morbidity associated with type 2 diabetes, affecting an estimated 22 million Furthermore, the drug demonstrated It is generally assumed that there will the ability to relieve symptoms in 61% be a class wide CV benefit, however Jard- type 2 diabetics in the US alone, according to an epidemiology study by Datamonitor of participants. iance’s label gives it a significant marketing Healthcare. advantage and physicians typically prefer [email protected], 6 Dec 2016 Published online 5 December 2016 to prescribe the drug that has data available whenever possible. CLICK Jardiance will primarily take share from CLICK You can read more on DPP-IV inhibitors (such as Januvia (sita- Read full story at: this topic at: gliptin) and sulphonylurea products. These http://bit.ly/2h3J6B5 http://bit.ly/2hoTHVa are currently the two most common treat-

14 | Scrip intelligence | 16 December 2016 © Informa UK Ltd 2016 HEADLINE NEWS

Sanofi Turns To Digital Transformation In Crisis-Hit China Vaccines Market A crisis can create opportunities when both manufacturers and service providers see the need to collaborate to meet China’s ever-changing regulatory demands. BRIAN YANG [email protected]

f there is one thing certain about China it is that there is no cer- Alibaba. A collaboration signed in September allows the French firm tainty. 2016 will possibly be remembered by many vaccine manu- to stay one step ahead as China tightens rules for tracking products Ifacturers in the country as a year of market disruption. A massive from manufacturing to distribution. product quality scandal that broke out in the spring has continued In September, the China FDA released a final opinion in which to wreak havoc on a complex and fragile system, denting both the regulatory agency requires makers to take the main responsi- small producers and large multinationals including Sanofi’s vac- bility for building a traceable system. cine subsidiary Sanofi Pasteur , who have had to adjust rapidly to a “Drug and device makers should follow good manufacturing much-changed operating environment. practice (GMP) to record all activities, and the records should be The impact has been so severe that the issues in China dragged true, accurate, total and traceable,” noted the official document, down the French group’s overall vaccines sales in emerging mar- “CFDA’s Comments on Promoting Drug and Food Makers to Im- kets by 2.2%. And for the first time in years, Sanofi’s growth in these prove A Traceability System.” market declined, despite outstanding double-digit growth from its Drugs and devices should also be traceable using their minimum pharma sales packages, added the agency. “That means that all changes should have records,” noted Ruan, who has also worked for Johnson & WHAT HAPPENED? Johnson in Shanghai as director of quality. April is traditionally a strong month for the vaccines industry in China, but this year it perhaps felt more like December, pitch dark NEW CHALLENGES and freezing. Alihealth’s product traceability system “Mashang Fangxin” has had its In that month, a mother-daughter family team in Jinan, Shan- own share of ups and downs. Previously, the Beijing-based health IT dong province was found to have distributed and sold vaccines firm obtained the exclusive rights from the CFDA to roll out a digital for over a decade across the country despite possessing no proper tracking system using a 20-digit code printed on external packaging. temperature-controlled facilities. In the aftermath of the affair, the However, that effort encountered fierce resistance from both government launched a strong clampdown, ordering the distribu- drug makers and wholesalers, who complained about the manda- tion of all vaccines to stop. tory requirement and added financial burden. “The chaos was created under a tightly-controlled planned The CFDA eventually relented and in a drastic about-turn economy,” noted Ku Lv, vice president of Liaoning Chengda Biotech stripped the rights from Alibaba, which had previously relied on Co. Ltd, a domestic vaccines maker. “After the scandal hit the indus- the business and invested heavily. The fallout hit Alihealth hard, ac- try, three government agencies jointly launched a crackdown, and knowledged Wang Peiyu, VP for its food and drug tracking business. a new regulation released April 25 essentially sent the sector back Drawing some hard-won lessons, Wang told the Kunming con- to a planned economy era,” the executive told participants in the ference that the company is now offering new QR code-based China Pharma Industry Development Summit, held Nov.30-Dec.1 tracking services free of charge and in closer collaboration with in Kunming. makers such as Sanofi. “The system is more incorporated with com- With a theme of “Reconstructing The Ecosystem for a Healthy panies’ situations, and the standards remain the same as before,” Future,” the conference was organized by the China Pharma Enter- Wang told Scrip on the sidelines of the conference. prise Management Association and the China OTC Association, and Sanofi has two main objectives in using the new system. One is executed by Sabailan, a new media industry publication platform. for its vaccines subsidiary Sanofi Pasteur to be able to fully trace Many rules contained in the new vaccines regulation are centered vaccines in China. Another application is to ensure drug safety on data and record traceability, which was where a transformation by fighting counterfeit versions in China of its best-selling blood started at Sanofi as it looked at how best to run its business in China. thinner Plavix (clopidogrel).The antiplatelet agent continues to “We actively test big ideas,” declared Alice Ruan, affiliate director enjoy stellar growth in the world’s second-largest pharma mar- of quality at Sanofi in China. These include adding new channels, ket, despite domestic generic competition. In the third quarter, innovative methods such as remote training, and the adoption of Plavix revenues increased 18% to €190m ($204.5m) in China, interactive tools, added Ruan, speaking at the same forum. compared to a 48% decline in Japan and roughly 10% drop in global sales. WORKING WITH ALIHEALTH Published online CLICK One of the new tools being used under the tighter regulatory re- 6 December 2016 Read full story at: gime is a digital traceability system based on an online platform built From the editors by Alihealth, a healthcare subsidiary of China’s e-commerce giant of PharmAsia News. http://bit.ly/2htn8YC

scrip.pharmamedtechbi.com 16 December 2016 | Scrip intelligence | 15 INTERVIEW

Bristol-Myers’ Mike Burgess Talks R&D Challenges, Portfolio Developments In 2017 Dr. Mike Burgess, the head of several disease R&D areas at Bristol-Myers Squibb, talks to Scrip on the side lines of the recent One Nucleus Genesis conference in London, UK, about the importance of a diverse portfolio, balancing R&D budgets and his industry-wide predictions for 2017.

LUCIE ELLIS [email protected]

r. Mike Burgess, senior vice presi- of trials ongoing – so it is not surprising dent of discovery medicine and that the majority of our R&D budget goes Dclinical pharmacology at Bristol- to the IO portfolio. But that is not to say Myers Squibb Co. and the head of the the non-oncology side is underfunded; company’s cardiovascular, fibrosis, immu- we have a budget that meets our needs noscience and genetically defined diseases in this area. (GDD) development teams, discusses why BMS is investing in areas outside of its core LE: How does the company manage these oncology expertise and what data readouts busy development areas, both oncology to expect from the company’s CV and fibro- and non-oncology, in parallel? sis pipeline next year. He also warns about MB: These areas are distinct from an op- the consequences of narrow R&D visions erational perspective – we are using dif- and being unprepared for exciting new sci- ferent people and approaching clinical entific developments to suffer setbacks in trials in different ways – but scientifically, early development. Dr. Mike Burgess philosophically and culturally they are Burgess, who is based in Princeton, New linked. There are significant synergies to Jersey, joined BMS as a senior VP in Janu- be gained with immunoscience and fibro- ary 2013 from fellow big pharma company Inc.: the lead program under this deal is for sis in respect to IO. We have done our best Roche, where he had held positions since intravenous CXL-1427, which is coming to to link the scientific thinking and under- 2008 and most recently acted as interim Phase II shortly. standing between these different thera- head of research and early development. [CXL-1427 works by transforming the peutic areas. compound nitroxyl once in the body and LUCIE ELLIS: BMS is currently in the spot- boosts heart muscle and vascular function.] LE: Are there any pipeline areas you would light for its immuno-oncology therapies, like to be more active in? but what else are you excited about in your LE: Why is BMS looking to diversify its port- MB: No, we have made a commitment to pipeline? folio now? be very focused in our approach. We are DR. MIKE BURGESS: Outside of oncol- MB: It is essential for the long-term health focused on the areas of IO, immunosci- ogy there is a real commitment at BMS to of the company to have R&D programs on- ence, fibrosis, CV and opportunistic efforts diversify the portfolio, so the non-oncol- going in several therapeutic areas. We have in genetically defined diseases. ogy portfolio is very significant. The areas strong revenues now and have increasing of prime importance are: immunoscience, venues from immune-oncology products, LE: What significant clinical milestones fibrosis and a new area for us of heart fail- but the health of the company overall is are coming up for the company in 2017? ure. Under immunoscience our focus is dependent on having a diverse portfolio. MB: In 2017 we expect to see data dis- on three major areas: rheumatoid arthri- Being too heavily invested in one area is closed in the public arena for several as- tis, systemic lupus erythematosus and in- a liability. Aside from that, we just have a sets. From the fibrosis perspective, we are flammatory bowel disease. All our agents decent pipeline outside of oncology and expecting data for our FGF21 asset, as in the immunoscience portfolio focus on many of these assets are first-in-class or well as data for the molecule we have just these three indications. best-in-class. Diversifying our portfolio is acquired from Nitto Denko Corp, ND-L02- In the cardiovascular setting we already not an aspirational goal for BMS – we have s0201, an siRNA against the heat shock have Eliquis (apixaban), which is doing ex- tangible assets we can develop. protein 47 (HSP47). tremely well on the market at the moment. We will also likely have data to present Behind this we have an anti-platelet agent LE: What R&D budget does the company for our CD28 agent and we have two op- and an anti-thrombotic factor XI agent in have for this diverse portfolio which in- tion agreements in fibrosis that are expect development. We also have clinical pro- cludes several early-stage candidates? to update next year: one with Galecto Bio- grams for heart failure. MB: We balance our budget and continue tech AB for a novel galectin-3 inhibitor in In this area, we announced a deal last to make a significant investment in R&D. development for idiopathic pulmonary year to acquire Cardioxyl Pharmaceuticals In the IO space, there are a huge number fibrosis (IPF); and the seconded is with Pro-

16 | Scrip intelligence | 16 December 2016 © Informa UK Ltd 2016 INTERVIEW

medior Inc. for PRM-151, which is in devel- NASH is a popular development area opment for IPF and myelofibrosis. Most of but we are focused on patients with the Xencor To these data releases will be in the second highest unmet need. Along with transfor- Raise $110m For half of 2017; it will be a busy time for BMS. mational medicines, part of BMS’s whole raison d’être is to go after patients with IO Pipeline LE: What would you highlight as the big- high unmet medical needs. For an area like gest R&D challenge currently, and how is NASH, we recognize the patients that re- Monrovia, California-based Xencor Inc.’s BMS meeting this challenge? ally need treatment are those with [fibrosis latest funding exercise is a public share of- MB: R&D is becoming increasingly com- scores of] F3 and F4 disease, as opposed to fering to raise some $110m after expenses petitive and the cycle of innovation is turn- those with F0 to F2. to advance its immuno-oncology pipeline. ing incredibly fast. The challenge is to be Xencor’s plan to publicly issue very cognisant of what the target oppor- LE: What industry trend or development 4,585,000 shares of its common stock tunity profile for a new drug needs to look are you most excited about now, and how is further evidence the clinical-stage US like. At BMS we are after transformative is BMS involved in this area? biopharmaceutical company and its products, we are not looking to develop MB: When you are in the middle of every- product pipeline are maturing. me-too drugs or products offering symp- thing it can be difficult to take a step out The NASDAQ-listed biotech Dec. 1 tomatic improvement. We are looking to and see where you are going. I think the said it filed a preliminary prospectus development medicines that fundamen- IO area has unlocked many things – for ex- with the US Securities and Exchange tally transform medical practice. Our chal- ample we are seeing new drug approvals Commission announcing the pricing lenge is to remain in the situation where come through in record times. Our own of an underwritten public offering we can make efficient calls on whether to agent, Opdivo (nivolumab), has secured 10 of 4,585,000 shares of its common discontinue molecules that don’t have the approvals in just under two years and that stock at an offer price of $24 each. legs to make it through clinical studies. is something we have not seen before. The net proceeds should be around Being in this position means we can apply Over the last few years I have seen in- $110m after expense and will be used our resources to the molecules that can dustry develop closer working relation- for working capital and general cor- succeed. Because BMS is only going after ships with regulators and thus transforma- porate purposes, as well as advanc- highly transformative medicines we have tive medicines are catching fire. This is the ing its lead compound XmAb5871 a little bit of leigh way – because we know greatest area of revolution for the industry through later stages of clinical devel- early that we have got a good medicine. in my mind. Also, like I mentioned earlier, opment and additional investment the cycle of innovation is turning fast. Five in its immune-oncology pipeline and LE: What do you expect to be the biggest or 10 years ago there was a lull, or at least a technology. hurdle for BMS progressing its later stage feeling of a lull, for pharma innovation and pipeline in 2017? now that is disappearing. We are seeing the Pipeline Promotion MB: I would call it a challenge rather than emergence of not only really good assets Founded in 1997, Xencor focuses a hurdle, but I would highlight an area of that are benefitting patients, but we are on discovering and developing fibrosis that we have a commitment in also seeing new technologies come to light engineered monoclonal antibodies and that is NASH (non-alcoholic steato- – such as CRISPR or the drugs active in the to treat autoimmune and allergic hepatitis). I think one of the challenges microbiome. These discoveries are coming diseases, cancer, and other condi- for the entire field is what the endpoints a lot more quickly than they used to. tions. Its product candidates include look like for this disease. From a regulatory XmAb5871, an immune inhibitor in point of view, liver biopsy is the current LE: What do you predict for the pharma Phase II development for the treat- standard – but the challenge is what does industry in 2017? ment of IgG4-related disease and the future look like. We recognize that liver MB: I try and avoid predictions, rather like systemic lupus erythematosus. biopsy may not be the ultimate measure horse racing, I’m notoriously bad at it. But I Amgen Inc. returned its rights to important to patients and physicians in do think, as ever, 2017 will bring some sur- XmAb5871 in October 2014 and the future, so the question is “How do we prises. Over the last couple of years every- Xencor narrowed the indications for the antibody, which targets CD19 work with regulators to understand that?” body got excited about CAR T-cells and and CD32b. But Amgen still has We are building a whole raft of non-in- now we have seen what has happened faith in Xencor’s platforms, having vasive measures into our clinical studies in for Juno over the last few weeks. agreed in September 2015 to pay NASH. There are also several partnerships Everyone gets excited about new tech- $45m up front plus up to $1.75bn with key academics or consortia that are nologies, which is great as we absolutely in milestone fees to use the biotech looking at the association between these need new technologies to help us treat firm’s bi-specific technology for the non-invasive markers and traditional liver these diseases, but we must remember development of antibodies targeting biopsy. We are some way out from have a there will be ups and downs. The compa- six undisclosed cancer and inflam- new definitive measure in NASH, but we nies and platforms that will win through, mation targets. are working on establishing the ground- will be those that stick at it. work for making that type of transition. Published online 5 December 2016 [email protected], 2 Dec 2016 scrip.pharmamedtechbi.com 16 December 2016 | Scrip intelligence | 17 BUSINESS BULLETIN

BiocurePharm Looks Beyond North America Via Sickle Cell Data Show Value Of Canada IPO Novartis’s Recently Acquired SEG101 With a business model that sets it apart Novartis AG’s recently acquired monoclonal antibody SEG101 showed a from other South Korean bioventures, statistically significant reduction in sickle cell pain crises at the antibody’s BiocurePharm plans to set up manufac- highest dose in the Phase II SUSTAIN clinical trial, a benefit one analyst turing facilities in North America and said could generate $1bn or more in annual revenue given the high unmet worldwide with local partners, and is need for the hereditary disease. The company has not indicated when it will launching a Canadian IPO in a bid to begin a Phase III program for SEG101 (crizanlizumab, formerly SelG1), transform into a truly multinational op- which inhibits p-selectin, but Novartis told Scrip that it “will continue the eration, its CEO says. “I believe we will development of SEG101 and will consult with relevant health authorities be the first South Korean bioventure to to discuss timelines.” The most advanced selectin inhibitor in development list shares in Canada,” BiocurePharm’s for sickle cell disease (SCD) is Pfizer Inc.’s Phase III pan-selectin inhibitor CEO and president Sang Mok Lee told rivipansel, which was licensed from GlycoMimetics Inc., but that candidate Scrip. “After debuting on the CSE, we is designed to treat patients when they are hospitalized for pain crises, not can move on to Nasdaq [in the US]. as a preventative therapy. SCD patients have abnormal hemoglobin that We were advised that it would be better results in sickle-shaped blood cells that stick together, causing blockages for us to proceed with our main activi- that lead to severe pain – and often hospitalization – as tissues are deprived ties in the US, while Canada serves as of oxygen. Patients generally die at a relatively young age due to organ dam- our bridgehead.” The company, which age caused by oxygen deprivation. The only cure is hematopoietic stem cell specializes in developing biosimilars, transplants, but many patients are too old or do not have a close enough ge- already set up a fully-owned Canadian netic match among family members to make a transplant possible. Hydrox- subsidiary, Biocure Technology Inc., in yurea is the only disease-modifying drug approved to treat SCD, but many Vancouver in November. This will serve patients cannot tolerate the drug’s side effects – cytopenia, headaches, skin, as the vehicle to launch the IPO in Can- gastrointestinal and other effects – or they do not see a big reduction in ada and will eventually acquire the par- vaso-occlusive crises. Hydroxyurea addresses the underlying cause of sickle ent company in South Korea in a reverse cell disease by increasing fetal hemoglobin to dilute the amount of abnor- takeover. In July, BiocurePharm reached mal hemoglobin in SCD patients’ blood. an agreement with Columbia Capital, [email protected], 5 Dec 2016 an investment firm in Canada, for the handling of the share listing in Canada. Lee noted the size of the float “won’t be large,” without elaborating. the end of 2014. His replacement, Alex hoping for a label that covers all pa- [email protected], 7 Dec 2016 Leech, led the company through more tients, regardless of positivity for CD30, Phase IIb testing and was keen to pur- though the Phase III ALCANZA study sue the product into Phase III but was was done in biomarker expressers. Data Itch-Focused Creabilis Finally unable to secure the financial resources. for Seattle Genetics Inc.’s Adectris in But all that is behind Creabilis now. “We the Phase III ALCANZA study secure Secures Its Future liked what Sienna offered. They are a new the drug’s bid – expected next year – for Sienna Biopharmaceuticals Inc. of Cali- company but they’ve got a proven track a new indication in CD30+ cutaneous fornia, a privately held medical dermatol- record of delivery and huge expertise in T-cell lymphoma. Adcetris (brentuximab ogy and aesthetics company, has acquired medical dermatology. So my board and vedotin) is currently approved for clas- Creabilis SA (more recently a PLC), for my investors decided this was a very good sical Hodgkin lymphoma and systemic an undisclosed upfront payment in cash option for the business,” Leech told Scrip. anaplastic large cell lymphoma. Seat- and stock, as well as additional payments “We feel Sienna are perfectly positioned tle Genetics and ex-US partner Takeda dependent on achieving specific regula- to develop the asset.” Pharmaceutical Co. Ltd. reported full tory and commercial milestones, which [email protected], 8 Dec 2016 results for the antibody-drug conjugate could exceed $150m. Creabilis has been in ALCANZA in CD30-positive CTCL, a ready to start Phase III trials for quite type of non-Hodgkin lymphoma, at the some time: initial Phase IIb data were re- Pivotal ALCANZA Trial American Society of Hematology annu- ported in 2013 when Immunocore’s Eliot al meeting, held from Dec. 3 to 6 in San Forster was at the helm of the company. Secures Adcetris’ Position Diego. Top-line results were released in Forster was unable to capitalize on the Regarding FDA filing in new CTCL early August. mixed results before leaving the firm at indication in 2017, Seattle Genetics is [email protected], 7 Dec 2016

18 | Scrip intelligence | 16 December 2016 © Informa UK Ltd 2016 HEADLINE NEWS

Mylan Plans Workforce Reduction After M&A And Price Scandal JESSICA MERRILL [email protected]

Mylan said it expects to cut less than 10% oping the details of the initiatives and that US Department of Justice to pay $465m of its workforce under a restructuring to further details will be disclosed as they are related to Medicaid rebates for EpiPen, streamline operations following a series finalized, including costs and savings. though no official deal has been finalized. of acquisitions. The news comes amid a Mylan has, indeed, been on an M&A The company’s stock dropped 4% to spate of negative publicity for the com- spree since 2014. Most notably, Mylan ac- $34.40 in mid-day trading Dec. 7. The stock pany, including a $465m settlement with quired the Swedish generic drug company has taken a battering over the last several the US Department of Justice over EpiPen. Meda AB for $9.9bn. earlier this year. That months, down 31% from where it was trad- mega-deal came on the heels of other ing Aug. 9 after announcing second quarter ylan NV will restructure its global acquisitions in 2015, including buying results and just before the EpiPen price scan- operations, resulting in layoffs that Mumbai-based Famy Care Ltd. for $750m dal hit fever pitch. Since then, the company Mare expected to impact less than plus contingency payments and the acqui- announced a patient assistance program to 10% of the global work force, the company sition of Abbott Laboratories Inc.’s non-US cover half the cost of EpiPen, or $300, for pa- revealed in a filing with the US Securities & developed markets specialty and branded tients with high out-of-pocket costs and an- Exchange Commission Dec. 7. generics business for $5.3bn. nounced plans to launch an authorized ge- The action is expected to streamline op- But the news also comes as Mylan has neric version of EpiPen at a cost of $300. erations globally, following a series of ac- faced backlash against the price of the Published online 7 Dec 2016 quisitions, the company said. emergency allergy treatment EpiPen (epi- Mylan employs roughly 35,000 people nephrine), which has put pressure on its View Mylan’s Busy Deal Strategy here: globally, which means some 3,500 jobs top specialty brand. In October, the com- http://bit.ly/2gw6nMy could be impacted. The firm said it is devel- pany said it reached an agreement with the

Scrip Awards Sponsored by Winner 2016 PPD’s Pharma Company of the Year Award

Scrip was impressed by Shire’s performance since its planned merger with AbbVie was called off in October 2014.

It has produced consistent growth, increased its R&D spend and acquired Baxalta to take a leadership position in rare diseases. This continued progress leaves it poised to enter the top 20 pharma companies worldwide by pharma sales Winner: Shire next year.

“We are pleased to be honored by our industry peers with this award. We welcome this important recognition of our continued growth and our deep and enduring commitment to serving patients and families across the globe that are affected by rare diseases and highly specialized conditions.” Scrip Awards Pharma intelligence | informa Dr. Flemming Ornskov, Chief Executive Ofﬁcer, Shire

scrip.pharmamedtechbi.com 16 December 2016 | Scrip intelligence | 19 POLICY & REGULATION BRIEFS

Gap Between Invoice And Real Prices Widening, Amgen/Allergan Target Lucrative QuintilesIMS Says Avastin Market With Another Global spending on medicine is set to reach nearly $1.5 trillion by 2021, but Biosimilar Filing including price concessions and re- Amgen Inc. and Allergan Inc. have filed their biosimilar version of bates drops that figure 25% to $1 tril- Roche’s anticancer Avastin (bevacizumab), ABP 215, with the European lion, according to a new forecast report Medicines Agency for the treatment of non-small cell lung cancer, target- from QuintilesIMS. The gap between ing another hefty portion of an originator molecule market that reached drug spending based on invoices and almost $7bn in 2016. Announced on Dec. 2, this is the second major filing for ABP 215 in the space of just over two weeks: the companies made a submission to the US Food and Drug Administration in mid- November. The two firms, which have a global collaboration agreement for the development of four biosimilar oncology drugs, said they believed this was the first bevacizumab biosimilar to be submitted to the EMA. Amgen executive vice-president of R&D Sean Harper described the move as an “important milestone” in the company’s efforts to expand its oncology portfolio. The EU dossier includes analytical, pharmacokinetic and clinical data, as well as pharmacology and toxicology data, the companies said. It is based on a Phase III comparative efficacy, safety and immunogenicity study that involved adult patients with non-squamous non-small cell lung cancer (NSCLC) and showed there were no clinically meaningful differences from the originator drug in terms of efficacy, safety and immunogenicity, they added. As well as lung cancer, Avastin is approved in the US, the EU and other regions for the treatment of meta-

Shutterstock: Sergey Nivens Sergey Shutterstock: static carcinoma of the colon or rectum, metastatic renal cell carcinoma, and other region-specific indications, the firms noted. Amgen/Allergan the real sale price after concessions for are not the only ones with Avastin in their sights: around a dozen other government plans and voluntary deals companies have biosimilar versions in their R&D pipeline, of which the with commercial insurers will contin- most advanced (in Phase III trials) are Pfizer Inc.’s PF-06539535, Sam- ue to widen in the next five years, ris- sung Bioepis Co. Ltd.’s SB8, Boehringer Ingelheim GMBH’s BI695502, ing to 36% in 2020, according to a new Biocad’s BCD-021, and Kyowa Hakko Kirin Co. Ltd.’s FKB238, accord- forecast report from the QuintilesIMS ing to the Informa Pharma Intelligence database, Biomedtracker. Am- Institute for Healthcare Informat- gen says it has nine biosimilars in its portfolio, including six MAbs: ABP ics. The report from QuintilesIMS, 215, ABP 980 (trastuzumab, Roche’s Herceptin), ABP 798 (rituximab; formerly called IMS Health, notes Roche’s MabThera), ABP 710 (infliximab; Janssen Pharmaceuticals Inc.’s that over the past decade, “the use Remicade), ABP 494 (cetuximab; Lilly’s Erbitux), and Amjevita/ABP 510 of off-invoice discounts and rebates (adalimumab, a version of AbbVie Inc.’s Humira), which was approved in contracts between manufacturers for marketing in the US in September. The identities of the other three and intermediaries has become more biosimilars have not been disclosed. widespread and pervasive with a wid- [email protected], 5 Dec 2016 ening gap between the so-called ‘gross’ spending on medicines and the ‘net’ realized revenue by manufacturers.” Invoice spending captures wholesaler nual review in 2015 that price conces- for commercial insurers, such as re- transactions at trade/invoice prices sions were increasing. The “Outlook bates and copay coupons, the gap in but excludes off-invoice discounts and for Global Medicines through 2021” gross spending vs. net sales for brand- rebates that reduce net revenue for report, released Dec. 6, provides a ed and generic drugs was 15% to 20% manufacturers. Net spending reflects forecast over the next five years – from between 2007 to 2011, rising to 28% manufacturer-recognized revenue af- 2016 to 2021 – and compares trends in 2016 and expected to rise further ter off-invoice discounts, rebates and to prior five-year intervals. Including to 36% by 2021. These figures derive price concessions. The widening gap concessions to government plans, for from an analysis of audited spending between list and invoice prices is a example Medicaid and the Veteran’s and net manufacturer sales. continuing trend; IMS noted in an an- Administration, and a range of deals [email protected], 6 Dec 2016

What Links Actimmune And Vertex’s Event Horizon? ANDY SMITH

Drug failures in Phase III and value-based pricing were two forces question of the value of its drug combination Orkambi (lumacaftor affecting Horizon and Vertex, respectively, last week. Biogen and and ivacaftor) for cystic fibrosis erupted into a public spat with the Teva have shown that value, at least, is a force to be argued with. Irish authorities. Having reached close to saturation in the US CF patient population, n astronomy an event horizon is the border beyond which not Vertex needed European expansion of Orkambi to meet its block- even light can escape the gravitational force of a black hole. In drug buster promises. However, after three profit warnings in the past year Idevelopment this type of barrier appears not to exist. Drugs like caused by sluggish Orkambi sales growth and a slower European up- MDCO-216 (Apo-A1 Milano) that failed once at Pfizer Inc. returned in take, the new specter of treatment discontinuations has also dogged order to fail again at another company. Orkambi. A failure by NICE to recommend Orkambi for reimbursement But the biopharmaceutical sector is approaching a much more in the UK in May was followed last week by the public disagreement significant event horizon, which requires the demonstration of cost- on Orkambi’s cost-effectiveness with Ireland’s National Centre for Phar- effectiveness in order to escape the pull of the black hole of formulary macoeconomics. Part of the disagreement centered on Vertex’s rejec- exclusion. tion of a risk-sharing agreement that would only pay Vertex for patients Horizon Pharma PLC announced the Phase III failure and discon- receiving sufficient clinical benefit from Orkambi. tinuation of Actimmune (interferon gamma-b1) in the rare inherited Vertex’s rejection of a risk-sharing agreement may have been pre- degenerative neurological disease Friedreich’s Ataxia (FA) last week. mature, since previous cost-containment efforts based on drugs that Horizon’s stock price finished the week down over 25% against the probably have limited cost-effectiveness have – like Actimmune – a NASDAQ Biotech Index’s 1% fall. The analysts from Citigroup described checkered history. Actimmune’s failure as the “removal of [a] meaningful potential growth driver” while those from Cowen described the disclosure as “disap- pointing” but stated that their “thesis is unchanged.” Limited efficacyshould result in a The Citigroup analysts probably had the better interpretation since Actimmune’s failure increases the scrutiny of, and Horizon’s depen- more restrictive label or pay-for- dency on, the company’s primary care franchise, which mainly com- performance agreements ... but will it? prises Duexis (ibuprofen and famotidine) and Vimovo (naproxen and esomeprazole). Both products are branded single-tablet combinations of generic analgesic and gastro-protective agents that are separately In 2002 NICE recommended against the reimbursement of the in- available over the counter in the US and offer only the convenience terferons (like Biogen Inc.’s Avonex (interferon beta-1a)) and Teva Phar- of a reduced pill burden to justify their higher prices. While the pharmaceutical Industries Ltd.’s Copaxone (glatiramer acetate) for multiple macy benefit managers of CVS Health Corp. and Prime Therapeutics sclerosis (MS) on clinical and cost-effectiveness grounds. As an interim LLC have recently included both products in their formularies, any measure the Department of Health agreed a number of individual premium negotiated over their generic equivalents will not be evi- agreements with manufacturers whilst the long-term cost-effectiveness dent until Horizon’s fourth-quarter financial report. The gamble on the of their drugs was assessed in a large publicly-funded study. A 10-year re- expansion of Actimmune’s label was therefore important to Horizon’s al-world study was started in 2002 which at its interim analysis after 5,600 orphan drug segment as it offered some respite from the value-based patients found a lower MS disease progression in the untreated control cost effectiveness pressures in primary care. group than in those treated with either Copaxone or the interferons. Dis- Actimmune is already approved in the two tiny and largely palliative agreements on the relevance of the data between the manufacturers treatment indications of chronic granulomatous disease and severe and NICE have subsequently prevented any of the performance-based malignant osteopetrosis. Horizon’s punt on FA and its failure in both price reductions that were envisaged as part of the study. primary and secondary endpoints has its roots in the convoluted his- Some gravitational forces are not strong enough. Actimmune’s fail- tory of Actimmune. Actimmune was the lead drug of InterMune Inc. ure in IPF in 2007 should have consigned it to the black hole of failed where for many years the majority of its sales – which reached $141m drugs. Orkambi’s limited efficacy in some CF patients should have re- in 2003 – were off-label in idiopathic pulmonary fibrosis (IPF). That was sulted in either a more restrictive label or pay-for-performance agree- until the FDA-requested the INSPIRE Phase III study in IPF which failed ments. My guess is that in the near term none of these will happen at the interim analysis prompting the divestment of Actimmune for and someone should have a word with Newton. In drug development, $55m and the settlement of the lawsuits surrounding its off-label pro- gravity is not a constant. motion and marketing. Published online 12 December 2016

ORKAMBI CHALLENGES Andy Smith gives an investor’s view on life science companies. He has Had Actimmune managed to squeak by Phase III in one of its larger been lead fund manager for four life science–specific funds, including orphan indication attempts it may still have raised questions on cost- 3i Bioscience, International Biotechnology and the AXA Framlington effectiveness because of its checkered history. That scenario would Biotech Fund, and was awarded the techMark Technology Fund Man- have resonated with Vertex Pharmaceuticals Inc. last week as the ager of the year for 2007.

scrip.pharmamedtechbi.com 16 December 2016 | Scrip intelligence | 21 PIPELINE WATCH

Scrip’s weekly Pipeline Watch tabulates the most recently reported late-stage, Phase III clinical trial developments for the more than 10,000 CLICK drug candidates under active research worldwide. To see changes to the Visit the Pipeline Watch webpage at progress of product candidates further back in the development pipeline, scrip.pharmamedtechbi.com for all and a table of the week’s product approvals, please visit our Pipeline the week’s changes to the industry’s R&D pipeline Watch webpage at scrip.pharmamedtechbi.com.

Selected clinical trial developments for the week 2–8 December 2016

LEAD COMPANY/PARTNER COMPOUND INDICATION COMMENTS Phase III Results non-small cell lung cancer (NSCLC), AURA3 study; reduced disease AstraZeneca PLC Tagrisso (osimertinib) second-line progression and improved PFS. Phase III Interim/Top-line Results BEFORE; Better than imatinib as Pfizer Inc./Avillion LLP Bosulif (bosutinib) Ph+-chronic myeloid leukemia first-line therapy. PROUD-PV; non-inferior to PharmaEssentia Corp./AOP Orphan ropeginterferon alfa-2b polycythemia vera hydroxyurea, and better Pharmaceuticals AG tolerability. TX-001HR (bio-identical estradiol postmenopausal vasomotor Met all co-primary efficacy and TherapeuticsMD Inc. and progesterone) symptoms safety endpoints. ASSIST-FL; Novartis’s first biosimilar Novartis AG biosimilar rituximab (GP2013) indolent non-Hodgkin’s lymphoma MAb, shown equivalence to reference rituximab. Teva Pharmaceutical Industries biosimilar rituximab (CT-P10) follicular lymphoma Equivalent to reference rituximab. Ltd./Celltrion Inc. Xultophy (insulin degludec and DUAL VII; non-inferior to insulin Novo Nordisk AS type 2 diabetes liraglutide) glargine with insulin aspart. Vonvendi (von Willebrand factor, Met primary endpoints in surgical Shire PLC Von Willebrand disease recombinant) procedures. Phase III Initiated ICARIA-MM; primary endpoint Sanofi/ImmunoGen Inc. isatuximab multiple myeloma is PFS. transfusion dependent beta Northstar-2; involving a gene bluebird bio Inc. LentiGlobin thalassemia therapy. Revance Therapeutics Inc. RT002 (daxibotulinumtoxinA) glabellar lines in adults. SAKURA-1,-2. Lipocine Inc./AbbVie Inc. LPCN 1021 (oral testosterone) hypogonadism A dosing validation study. Phase III Announced ANGEL-MS, a long-term GeNeuro SA/Servier SA GNbAC1 (MAb against MSRV-Env) multiple sclerosis extension study. Source: Biomedtracker

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Asceneuron SA, a company focused on directors. With more than 20 years’ experi- Robert Tjian, a member of the National neurodegenerative diseases, has appointed ence, Norden is the managing director of Academy of Sciences, has joined Nurix J. Michael Ryan chief medical officer. Ryan G9 Capital Group LLC and serves on vari- Inc.’s board of directors. He was a co- has more than 15 years’ central nervous sys- ous boards including NanoString, Royalty founder of Tularik with Dave Goeddel and tem clinical research experience and joins Pharma and Univision. Previously, he held Steve McKnight; and most recently served the company from Novartis Pharmaceuti- senior positions with Wyeth/American as president of the Howard Hughes Medi- cals Corp. At Novartis he was vice president Home Products – most recently as Wy- cal Institute (HHMI). in the neuroscience development franchise eth’s senior vice president and chief fi- and therapeutic area head for neurodegen- nancial officer. Renova Therapeutics has named Cath- eration. Ryan has also held various senior erine Bovenizer chief financial officer. clinical research and development posi- Pamel Fralick, former president and CEO Bovenizer joins the company with 20 tions at several multi-national companies of the Canadian Cancer Society, has been years’ experience in financial manage- including Pfizer, Wyeth Research and MSD appointed Innovative Medicines Can- ment for various public and private bio- Research Laboratories (known as Merck Re- ada’s president – effective immediately. tech and software companies. Most research Laboratories in the US). Prior to the Canadian Cancer Society, Fral- cently, Bovenizer was the vice president ick spent five years as president and CEO of finance and chief accounting officer at Bayer has appointed Robert LaCaze ex- of the Canadian Healthcare Association Apricus Biosciences. ecutive vice president of its new oncology and six years as CEO of the Canadian Physi- strategic business – effective Feb. 1, 2017. otherapy Association. UCB has announced several changes LaCaze is senior vice president, head of the in the composition of its board of direc- global oncology therapeutic area within Biomunex Pharmaceuticals has appoint- tors. By the next annual general meeting the pharmaceutical division at Bayer and ed Sebastian Amigorena key scientific of the company to be held on April 27, in his new role he will be a member of the advisor and Dragan Grabulovski key stra- 2017, Gerhard Mayr will have reached pharmaceuticals division’s executive com- tegic advisor. Amigorena is a research direc- the statutory age limit and will step down mittee. Before Bayer, LaCaze was senior tor at the National Center for Scientific Re- as director and chair of the board. He vice president, head of product and port- search and director of the Inserm Immunity has been UCB’s chair for four years and a folio strategy at Bristol-Myers Squibb, US. and Cancer Unit at the Institut Curie in Paris. board member for more than ten years. Grabulovski is an advisor in pharmaceutical Evelyn du Monceau, currently vice-chair, Entasis Therapeutics, a company fo- biotechnology at Grabulovski Consulting will succeed him. Meanwhile, Pierre Gur- cused on anti-infective products, has Services. Previously, he was chief scientific djian, independent director, will become appointed Greg Norden to its board of officer and co-founder of Covagen AG. vice-chair. Scrip ELEANOR MALONE @SCRIPELEANOR LUCIE ELLIS @SCRIPLUCIE YING HUANG [email protected] [email protected] [email protected] ALEXANDRA SHIMMINGS @SCRIPALEXS LUBNA AHMED @SCRIPLUBNA JUNG-WON SHIN [email protected] [email protected] [email protected] SUKAINA.VIRJI @SCRIPSUKI PAUL WILKINSON @PAUL__WILKINSON BRIAN YANG [email protected] [email protected] [email protected] ANJU.GHANGURDE @SCRIPANJUG JOHN HODGSON @SCRIPJOHN [email protected] [email protected] All stock images in this publication MANDY JACKSON @SCRIPMANDY MIKE WARD @SCRIPMIKEWARD courtesy of www.shutterstock.com [email protected] [email protected] unless otherwise stated. JOANNE SHORTHOUSE @SCRIPJO PETER CHARLISH @PETERCHARLISH Customer Services [email protected] [email protected] Tel: +44 (0)20 7017 5540 FRANCESCA BRUCE @SCRIPFRANCESCA JOHN DAVIS @JOHN023DAVIS or (US) Toll Free: 1 800 997 3892 [email protected] [email protected] Email: [email protected] STEN STOVALL @STENSTOVALL EMILY HAYES @EMILYKATEHAYES [email protected] [email protected] To subscribe, visit IAN SCHOFIELD @SCRIPIANS JESSICA MERRILL @JESSCIAMERRILL scrip.pharmamedtechbi.com [email protected] [email protected] To advertise, contact ASHLEY YEO @ASHLEYPYEO JOSEPH HAAS [email protected] [email protected] [email protected] Scrip is published by Informa UK Limited. MARY JO LAFFLER IAN HAYDOCK ©Informa UK Ltd 2016: All rights reserved. [email protected] [email protected] ISSN 0143 7690.

scrip.pharmamedtechbi.com 16 December 2016 | Scrip intelligence | 23 Pharma intelligence

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