The Man Reshaping Takeda Expect Industry To Step Up Drug Brexit: What Can The Life Sciences Christophe Weber became the first Pricing Self-Regulation In 2017 – PwC Industry Do About It? non-Japanese and first corporate Rick Judy expects pharma companies Restrictions on the free movement outsider to be president and CEO at the to announce more social contracts of people, products and finance will more than 230-year old company (p4) with consumers (p6) impact the life science sector (p16)

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Scripscrip.pharmamedtechbi.com Pharma intelligence | informa gen’s stock regained the lost ground Dec. 20, however, to close at $285.41. Beyond the longshot M&A thesis for Bio- gen, the appointment brings some uncer- tainty, because Vounatsos has not held a chief executive position before and he has not been with the company long. Vounat- sos joined in April to fill the vacancy left by Tony Kingsley and to oversee Biogen’s global commercial strategy. He previously completed a 20-year tenure at Merck & Co. Inc., where he held roles of increasing re- sponsibility in Europe, China and the US. His last job at Merck was president of the primary care business and Merck customer centricity. Scangos said during a Dec. 20 conference call that Vounatsos stood out in a search that attracted a lot of high-caliber candi- Shutterstock: kirill_makarov Shutterstock: dates. “Our board wanted a CEO with strong leadership skills, a track record of operation- al success across multiple geographies and Biogen CEO Pick Vounatsos Suggests a focus on innovation,” Scangos said. “Michel was on the very first list of candidates, and as we’ve progressed with the search, he A Return To Commercial Focus consistently stood out as our top choice.” JESSICA MERRILL [email protected] INTERNAL REVIEW PLANNED Biogen’s Chief Commercial Officer Michel keted products, particularly in the core For his part, Vounatsos would not provide Vounatsos will succeed CEO George Scan- area of multiple sclerosis, and fill a late- much in the way of detail on his vision for gos effective Jan. 6. The appointment of stage pipeline gap. generating growth from current products the longtime Merck executive appears to Biogen announced the new CEO after or filling the pipeline through deal-making. suggest a renewed emphasis on the com- market close Dec. 19 and investors reacted He said his first priority would be to con- mercial landscape for a big biotech that with the stock dropping 2.7% on the news duct a thorough business assessment and has recently played up R&D. to $278.77 in after-hours trading, possibly report back to investors, likely within three over concerns about what the appointment to six months. he appointment of Biogen Inc.’s might mean for a potential sale of Biogen. The immediate priority will be the approv- Chief Commercial Officer Michel Speculation increased, when Scangos an- al and launch of Spinraza (nusinersen) for T Vounatsos to succeed George nounced his intention to step down as CEO children with spinal muscular atrophy (SMA), Scangos as CEO effective Jan. 6 sug- earlier this year, that the company might he said. Biogen, which is developing the an- gests a renewed emphasis on commer- find a buyer. Now, with the appointment of tisense drug with Inc., cial growth at a time when the company a new CEO, some investors may have felt the recently completed a rolling NDA submission needs to squeeze growth out of its mar- chance of such a move were less likely. Bio- CONTINUED ON PAGE 8

BROUGHT TO YOU BY THE EDITORS OF PHARMASIA NEWS, START-UP AND SCRIP INTELLIGENCE IN THIS ISSUE Season’s Greetings Wishing our readers a joyful holiday season and all the best for 2017

The next issue will be 6 January 2017. For online access please contact customer services at +44 (0)20 7017 5540 or [email protected]

COVER / Biogen CEO Pick Vounatsos Suggests A Return To from the editor Commercial Focus [email protected] 3 Trump’s Rx For The Drug Industry: Take Two And Have No Idea What Will Happen In The Morning We reach the last issue of Scrip this year much as we did 4 Christophe Weber: last year: in a flurry of pharma industry deal-making. The Man Reshaping Takeda As I write, rumors that was preparing a tasty offer for Switzerland’s have been superseded 6 Expect Industry To Step Up Drug Pricing by Actelion’s curt announcement that it is in talks – Self-Regulation In 2017 – PwC once again – with Johnson & Johnson. Some believe Actelion could be sold for up to $30bn, which would 7 Purdue Signs Two Deals To Diversify Portfolio put it within spitting distance of the biggest pharma 9 Sanifit Utilizes Calcium Phosphate Chemistry To Treat deal this year, Shire’s acquisition of Baxalta. Rare Renal Disease Meanwhile, Novartis has pushed through a num- ber of transactions including that of Ziarco (see p10) 9 ’s Eucrisa Approval By FDA Adds New in dermatology and Encore Vision in ophthalmol- Dermatology Anchor ogy, and has just put $2.9bn on the table 10 Business Bulletin for aesthetics business LifeCell. It’s not just M&A – 11 Lilly’s Insulin Discounts Target High-Deductible companies are also rushing to seal collaboration and Insurance Gaps licensing deals, including Purdue (see p7). There has also been a noticeable uptick in execu- 11 Hanmi Toughens Controls As Employees Arrested tive churn. We’ve seen Alexion’s David Hallal depart For Insider Trading in less than a blaze of glory (see p10), while Cempra, Kiadis, Innate Pharma, Impax and Teva Generics are 12 The Competition Begins To Host The Post-Brexit EMA some of the firms kissing goodbye to their bosses. 14 Bristol Closes, Consolidates R&D Sites Under Happy holidays all. Cost-Containment Plan

14 Concern Over COPD Update

15 Policy & Regulation Briefs 16 Expert View: Brexit: What Can The Life Sciences Industry exclusive online content Do About It? 14 R&D Bites Oncology Scorecard – Who’s Succeeding At Cancer 19 Daiichi Sankyo Lays Out Priorities Drug Development Using Pharmapremia data, we analyze performance metrics 20 Turkey Adopts New Investment Incentives But for a select group of leading cancer companies to see where Pharma Wary the sticking points are and who is winning at industry’s most important race. 21 Stockwatch: A Biopharma Nativity Play http://bit.ly/2hzI3Zx 22 Pipeline Watch Neovacs CEO Outlines Clinical Timeline For Lupus Drug Miguel Sieler, CEO of 25-year-old French company 23 Appointments Neovacs, chats with Mike Ward, global director of content for Informa Pharma Intelligence, about the company’s early lead in immuno-stimulation research. http://bit.ly/2hR6yiw @scripnews /scripintelligence

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2 | Scrip intelligence | 23 December 2016 © Informa UK Ltd 2016 HEADLINE NEWS

Trump’s Rx For The Drug Industry: Take Two And Have No Idea What Will Happen In The Morning M. NIELSEN HOBBS [email protected]

To call the incoming US president unpre- the possibility is a definite even as it feels as On the stump, Candidate Trump made dictable would be an understatement, though the entire country is still the cast of numerous statements that went against but that doesn’t mean that industry a reality TV show. There has never been a the Republican mainstream, most notably shouldn’t know what to expect. president with such open contempt for tra- for pharma firms a suggestion that the ditional political mores, and there are those government should negotiate drug prices uspension of disbelief is a key element who maintain that combining the power in Medicare. Another pledge, one that was to the success of many dramas, so it of the presidency with Trump’s volatile per- actually on his website for a time, would Sseems fitting that even as the results sonality could produce cataclysmic results. allow importation of drugs from countries of one of the most dramatic elections in US The fate of the world is beyond the scope of where products are cheaper. history became apparent, hardly anyone our discussion here, but suffice to say that But as has been the case for much of could believe it. The Coastal Elites – feel- those in the industry who are most worried Trump’s populist rhetoric, from taxes to banking regulation, firebrand campaign speeches have cooled to more doctrinaire policy proposals. To wit, the transition agenda released after the election talks about reforming FDA, not cracking down on Rx prices. That’s not to say that drug firms have nothing to fear from a Trump administra- tion when it comes to drug prices, even as stocks in the sector went on a giddy rally after the prospect of the Clinton presidency, and its sharp attention to pricing, disappeared. The idea that drug prices are too high remains one of the few areas of bipartisan agreement among voters, and the bully Shutterstock: JStone Shutterstock: pulpit of yore is now the bully Twitter ac- ing every bit like the blue parentheses the about a Donald-induced apocalypse are count, so it’s not hard to imagine Trump country’s population centers resemble on likely no longer thinking about pipeline per- burnishing his populist credentials by the electoral map – can be forgiven for ach- formance or quarterly sales targets; instead, excoriating the next example of Rx price ing like a drug sponsor does when a prod- their focus on medications revolves around gouging. Some within industry think that uct is rejected by FDA even after it’s been deciding what products to stock in their un- problem will extend beyond 140 characters endorsed by an agency advisory commit- derground shelters. and are urging companies to take proactive tee. Their data told them it would succeed, steps on pricing before they again face the and they won a popular vote, but they are TWITTER V. POLICY prospect of genuine reform efforts. still left profoundly disappointed and won- But even executives not worried about Ar- dering what to do next. Sometimes life it- mageddon and simply trying to plan for the REPEAL AND REPLACE self can resemble being regulated by FDA. new administration are asking themselves: The biggest near-term risk to industry from Now that Donald Trump has been ap- how much do I need to think about approv- a Trump presidency appears to be uncer- proved for domestic and external use, the al and reimbursement regulations, and how tainty created by efforts to repeal and re- will need to be much do I need to need to think about PO- place the Affordable Care Act. ready for the benefits and side effects of that TUS’ Twitter? The answer is that both issues The Affordable Care Act (ACA) brought prescription. The efficacy is immediate, but will likely require a fair bit of attention, but health insurance to tens of millions of Ameri- the challenges are significant as well. Last the good news is that even as the public as- cans, expanding the number of customers year, we recommended that companies be- pects of Trump’s persona are without politi- for pharmaceutical companies. If repeal and gin preparing for the possibility of a Trump cal precedent in the US, his administration’s replace results in a lot fewer people with presidency but the circus atmosphere of policy approaches are shaping up to be al- coverage, that could mean a lot less medica- the ensuing campaign made such reasoned most generically Republican in the areas that tion dispensed. And while industry is aware forethought difficult at best. Now, though, pharma companies care about most. CONTINUED ON PAGE 8

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Christophe Weber: The Man Reshaping Takeda IAN HAYDOCK [email protected]

Christophe Weber became president and IH: So do you think this is now water under there were no real global brands, so ev- CEO of Japan’s Takeda Pharmaceutical the bridge? ery country, every region was generating on April 1, 2015, in the process becom- CW: People are now more used to me and its own strategy independently from the ing both the first non-Japanese and first I have created a lot of bridges with em- others, because of the historical set up. corporate outsider to hold the position ployees and externally. You know, in Japan What we decided was to globalize some at the more than 230-year old company. relationships are very important, and it can areas, for example R&D, and reset ambitions He has since initiated a ground-up refo- take around 18 months or so for people to here to define what innovation means. We cusing and restructuring that will alter get used to someone new. I think people confirmed we want to be an R&D-driven the fundamental shape of the company are much more comfortable now with me company with an R&D engine serving the while retaining its core identity. and my stance. People could see that I was world with products with global potential. very committed to the company. We also globalized manufacturing which was in three organizations and lacking a lot IH: Once you became CEO, how did you of potential synergies. go about getting to know the company What was more uncommon was that we and its people and communicating your also globalized the values of the company, vision? which were very strong. We defined that in- CW: From day one I was really account- ternally as “patient, trust, reputation, business.” able for the whole company…and that We trained everybody around the world on was a very powerful way as I didn’t have this. Every manager around the world who to think about “Step 1, Step 2, Step 3.” I joins the company spends one week in Ja- pan now to understand the company. Christophe Weber spent the first few months [from April to July 2015] after joining just understand- Some areas we wanted to keep more ing the company, the culture, the employ- local - the [country] general managers are IAN HAYDOCK: What made you decide ees inside and outside Japan, because really key to deliver the right service to the to accept the offer from Takeda, and what something that is misunderstood [about market and we believe that every country did you see as the main challenges for the Takeda] is that 70% of our employees are is very different…we wanted to keep this company at the time you took over? outside Japan. agile and customer-centric. CHRISTOPHER WEBER: I was really at- I had a very significant listening period So we wanted to globalize when we get tracted by the history and strong reputa- and I held a huge number of workshops to the benefit and keep it local where appro- tion of the company inside and outside get a good feel about what is working well, priate to find the right balance. Japan, but at the same time it had not what should be our direction, what we IH: What were the main factors behind the completely globalized and had lost some could improve, and how we could reshape ranking, like many Japanese companies. the company. It was very intensive but very decision to focus on selected therapeutic So it was a very exciting challenge to important. areas and why do you see these as provid- make Takeda more competitive. I had a ing attractive opportunities? good relationship with the chair [Yasu- IH: Did the feedback inform your subse- CW: It’s a very strategic and long-term deci- chika Hasegawa] and the people I met at quent views? sion. We stepped back and asked what is the the time, and I felt we could work together. CW: Yes, because it gave me confirmation environment asking - and that is significant that of areas to improve, we organized innovation. The winner will be the company IH: There was some initial controversy to work streams with teams that made rec- able to deliver truly innovative medicines. the appointment of a corporate outsider ommendations for change. This period We looked at our strengths and weak- and non-Japanese. was very critical to define the strategy of nesses by therapy area because Takeda CW: Yes, there was certainly a healthy de- the company and how it should be orga- was doing screening in the traditional bate! There were some questions at the nized to execute this. way and developing the hit molecules first AGM but I think it was more linked across therapy areas. But the risk is that to the fact that people were a bit taken IH: Did you feel Takeda had an appropri- there is no real innovation and you may by surprise more than the fundamental ately balanced business both geographi- not be the first. challenge of me being a foreigner. Frankly cally and by scale at that time? Our approach now is to focus on a few I did not experience any big push-back ei- CW: It depended on the area. Takeda has areas where we believe we can be the ther internally or externally. been an extremely diversified company, leading company or one of the leaders. We

4 | Scrip intelligence | 23 December 2016 © Informa UK Ltd 2016 HEADLINE NEWS

start from the disease and the biology and but I am very pleased it has been very suc- tion. In a way it will free up our ability to then design a molecule against this, find- cessful so far. decide which assets to take forward. ing partners if we cannot do this ourselves. Entyvio is really delivering well every- So it’s a big change and it took a while where, including emerging markets, where IH: How do you see emerging markets - to narrow down to three areas [oncology, we have reconfirmed our commitment in another major business pillar - developing CNS and gastrointestinal] plus vaccines. our strategic refocus. We want to be pres- particularly given the economic slowdown Takeda has been active in diabetes and ent in many countries but not everywhere. in China? cardiovascular for a long time, with some We are still much more diverse [in prod- CW: Over the long term we see the significant products, and we will not drop ucts] than many companies but Entyvio is emerging markets as still very attractive these, but we felt the three new core areas now our biggest product. because they are driven by population were the most attractive and where we We have global products we want to and pure demand for better treatments, could have the biggest success. launch everywhere but on top of these, and this will generate long-term growth We also looked at our financial resources our local businesses can still develop their and demand. and how much we could commit to R&D portfolios through diverse products pro- The way I see emerging markets is not as [about $3.3bn annually at present] and we vided it is margin-accretive, in line with our a smooth growth line, you will always have found a balance with this. broader agenda. cycles but the overall trend is positive and that’s why we remain committed. IH: Was it the market potential or unmet IH: Any comments on the recent rumours We used to be in value brands [in emerg- medical needs in those focus areas that that Takeda is in the running to acquire Va- were most attractive? leant’s Salix business? ing markets] but we are now launching our branded, patented products on top of CW: For sure, also internal capabilities CW: We will give a lot of information [on these and building our capabilities, helped and our market understanding and com- any potential] deal when we have some- by a new market access strategy. So this petition intensity. For example, oncology thing to disclose! We are very disciplined will diversify our growth opportunity. is already big for Takeda and was a “no- internally and we have no comment, but brainer” even though it is highly com- when we disclose something we will pro- IH: Would you consider M&A to boost your petitive. But we will not go everywhere vide a lot of information. emerging markets presence? in oncology. CW: We will always look at opportunities In CNS we don’t have a large portfolio IH: What led to the huge decision to fun- but we are not in a geographical expan- but we have invested for many years and damentally restructure R&D - were fixed sion mode, so we prefer to build our pres- we feel the unmet need is very high and costs and infrastructure inappropriate? ence where we are already strong, so we the competition is less because it’s hard. GI How do you see outsourcing working in don’t really need to make acquisitions. But is more a reactivation of our R&D as Take- practice? any that are made would be to reinforce da was at the origin of the proton pump CW: This is linked to our therapy area where we already have a strong presence. inhibitor but there were disinvestments focus; we have to readjust our capac- some a long time ago. ity. It’s more a quality-based process. We IH: How do you see Takeda’s new medicine Stepping back, it was logical but it was believe it’s good to concentrate our sites access initiatives helping branded sales in not easy to select these focus areas and to become more efficient because if you emerging markets? to move away from others where we have have project teams across five sites, it’s CW: We are focusing on branded prod- been for a long time. very difficult. So we will concentrate discovery and ucts with a high medical value, mainly IH: Within these areas can you talk about R&D in Japan and Boston, Japan mostly on Entyvio and Ninlaro. We are developing why you see Entyvio and Ninlaro becom- CNS and Boston on oncology and GI. The patient assistance programs with NGOs ing so successful? other big change is the partnership with and we will adjust product prices based CW: In 2014 it became clear that Entyvio PRA Health Sciences Inc., which will allow on the income of the population and [vedolizumab, for ulcerative colitis and us to resource flexibly depending on the what people can pay, which will help us Crohn’s disease] was a major innovation pipeline, we don’t want to be constrained to drive access. and had potential for a global launch so by fixed costs and want these to be adjust- We have opened a new office in Kenya we are launching as quickly as possible ed according to the pipeline. to promote access in sub-Saharan Africa everywhere. It’s not a traditional CRO relationship, it’s and help develop infrastructure. It will be It is a new agenda for Takeda and we are very integrated partnership and we will part of country general managers’ respon- repeating a global launch with Ninlaro [ixa- share pipeline developments with PRA in sibilities to drive access as part of the busi- zomib, for multiple myeloma] and so I think advance. Takeda was actually outsourcing ness model. it has been a huge transformation as his- a lot already. Published online 12 December 2016 torically we were a primary care company Another thing is that we want to avoid and we have become more a specialty care developing sub-optimal assets just be- This article forms part of Scrip 100 2016’s company, and it has been a huge shift in cause we have the [internal] capability - we Leadership chapter, in which the pharmaceu- medical and sales capability for example, want to put the bar very high for innova- tical industry’s c-suite talk exclusively to Scrip. scrip.pharmamedtechbi.com 23 December 2016 | Scrip intelligence | 5 HEADLINE NEWS

Expect Industry To Step Up Drug Pricing Self-Regulation In 2017 – PwC As industry begins to organize around broader self-regulation on drug pricing, PwC Partner Rick Judy expects pharma companies to announce more social contracts with consumers. Industry self-regulation on prices is one of 10 top health issues for 2017 identified by the consulting firm.

JESSICA MERRILL [email protected]

nitiatives around industry self-regulation on drug pricing will gain value,” Judy said. “Regardless of the direction in which the adminis- momentum in 2017, according to an annual trends report released tration takes us, we think a lot of these concepts have enough mo- Iby PwC Dec. 15 that outlines health industry predictions for the mentum and enough impact that we think the concept of value will year ahead. continue to dominate in 2017.” Three years of sustained pricing pressure on drugs may result in new These initiatives will include more value-based contracts between restrictions in 2017, although those restrictions might be implement- payers and pharma companies. “The training wheels are coming off ed by industry rather than regulators, the consulting firm said. value-based payments,” Judy said. Value-based contracts are gaining “What we are seeing is that the industry is generally beginning to or- momentum in the US, with several new contracts signed in 2016, but ganize around self-regulating, around building solutions to get some execution challenges continue to limit use of them more broadly. of the pricing back into check,” PwC Partner, Health Industries Advisory PwC’s report also applies to physician payments, and particularly to Rick Judy said in an interview. “There is a new realization within the the Centers for Medicare & Medicaid Services; 2017 will be the first per- folks in the pharma sector that they would rather self-regulate than formance year for the Medicare Access and CHIP Reauthorization Act have regulations dictated to them.” of 2015, the physician payment reform law known as MACRA. PwC predicts more pharmaceutical manufacturers will develop “so- cial contracts” with consumers as part of their pricing strategies, along ‘There is a new realization within the folks the lines of the one Allergan PLC unveiled earlier this year. In Septem- ber, CEO Brent Saunders vowed Allergan would not engage in preda- in the pharma sector that they would tory pricing and promised to limit price increases to single-digit per- centages taken no more than once a year. rather self-regulate than have regulations Saunders appeared recently at the Forbes Healthcare Summit in dictated to them’ and urged more pharma companies to consider similar poli- cies now before regulators decide to act. While some in the industry may have been lulled into a false sense of security following the elec- tion of Donald Trump as President in November, Saunders warned his peers to remember that Trump’s populist message could come down When it comes to healthcare policy, the year 2017 is also likely hard on the pharmaceutical industry. to be dominated by the Affordable Care Act, since President-elect Trump clearly can have as much of an impact on a company’s stock Trump has vowed to make repealing and replacing the ACA one of price with one tweet as Hillary Clinton did, he said. his top priorities. “It’s unknown what [Trump] is going to do or what his team is go- “There is a lot still unknown out there about what repeal-and-replace ing to do in regards to pricing,” Judy said, but PwC said the threat of will mean,” acknowledged Judy. “There is certainly a movement toward legislative action remains real. California voters only narrowly rejected making it a more consumer-centric model, a more free-market-based Proposition 61, a measure that would have prohibited state health system, less government.” plans from paying more for drugs than the US Department of Veteran PwC included the fate of the ACA as one of the top healthcare priori- Affairs, on election day. Other states have expressed interest in consid- ties for 2017. “The thing that is the most on the minds of health care ering similar proposals. executives that is a shift from the previous administration is the notion Others in the industry have also been advocating for more transpar- of access,” Judy said. “That’s the biggest unknown as you repeal and ency when it comes to drug pricing, with pharmaceutical companies replace ACA, what is going to happen to the 20 million people that complaining that most of the increase in prices are taken out across have gained access in the last several years through the exchanges, the supply chain, often in the form of rebates, discounts and fees. what is going to happen to their access and the downstream effects of The issue of pricing gets to the heart of PwC’s trend report this year, not having as much access.” which is that regardless of the uncertainty a Trump administration Other priorities for the sector in 2017, according to PwC, will be the brings, the focus on value over volume will continue. integration of more emerging disruptive technologies, more invest- ment in fighting infectious diseases, particularly through public-private THE MOVEMENT TOWARDS VALUE CONTINUES partnership and investment in new diagnostic tools, more partnering “The crux of our report really summarizes the trends going back to and collaborations, and a growing awareness of the role nutrition plays this concept of value and the healthcare industry really having a lot in health. of momentum that has been set forth for the past decade around Published online 15 December 2016

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Purdue Signs Two Deals To Diversify Portfolio LUCIE ELLIS [email protected]

Purdue Pharma has made headway this month on its 2016-initi- Butcher added that this deal also gives Purdue the flexibility to ated plans to diversify the company’s R&D portfolio away from maximize the value of its development pipeline by innovating the pain therapy space, having actioned two collaborative deals products with diverse drug delivery approaches. “This technol- with Exicure and AnaBios. ogy platform in particular lends itself well for rapidly bringing forward important medicines in a multitude of disease areas,” urdue Pharma LP and Exicure Inc. have entered a strategic re- he said. search collaboration, option and license agreement to discover AST-005’s SNA construct enhances cellular uptake compared to Pand develop a treatment for psoriasis. nucleic acids not in the SNA-format, Purdue highlighted. The treat- The deal also covers R&D for other diseases amenable to a gene ment “combines the targeted benefits of biologics with the ease of regulation approach utilizing Exicure’s spherical nucleic acid (SNA) application of topical steroids,” Butcher said. technology. Purdue, upon exercise of the options, will obtain full AST-005 will be the first topical therapy targeted toward demon- worldwide development and commercial rights to Exicure’s lead strating reductions in TNF-alpha for potential treatment of psoria- product AST-005 and rights to three additional collaboration tar- sis. Purdue will continue to study AST-005 in patients with mild-to- gets with associated intellectual property. moderate psoriasis – initiating further clinical studies in 2017. Purdue told Scrip in a recent interview it was expecting to an- While Purdue is not currently disclosing the other potential nounce a large deal or acquisition by the end of 2016. Kathryn diseases it will target with drug candidates licensed from Exicure, Gregory, executive director of licensing and business development Butcher said: “They could be completely different from psoriasis or at Purdue, said the company was looking for anything from “very dermatology as the technology platform allows us to consider mul- early-stage, innovative, non-opioid, non-NSAID (nonsteroidal anti-in- tiple therapeutic areas and multiple methods of delivery.” flammatory drug) pain products all the way through to anything on the market that is a good fit in terms of our commercial sales force.” MORE DEALS TO COME The company’s other recent deal was in the non-opioid R&D space. Butcher told Scrip that Purdue has done a record number of deals Purdue launched its search for partners or asset acquisitions ear- in the last two years since Timney took over as CEO, compared to its lier this year; these two recent deals are part of CEO Mark Timney’s historic activities. But the company is not finished yet. five-year plan to diversify Purdue’s portfolio away from the opioid “Outside of CNS, based on the leadership team we have built, we pain space. Timney joined to company in 2014 from Merck. He told can go anywhere,” Butcher said. “We are not interested in vaccines or Scrip in an interview earlier this year that Purdue has “fundamen- oncology because everyone else is there already. We are going to be tally changed its business model; we are now doing less internal driven by the asset and let the asset lead us onward, rather than say discovery and have instead built up a business development group we want to enter a pre-specified therapeutic area. This method is so that people know what Purdue is and that we are open for busi- throwing up much more interesting ideas in science for us.” ness.” He said the company was focused on growing its pipeline away from its current, “very narrow,” focus on abuse-deterrent opi- ANABIOS PACT oids with extended-release formulations. Purdue also signed a deal earlier this month with AnaBios Corp. Under the terms of agreement, Exicure received an upfront that will focus on non-opioid, non-NSAID compounds for the payment, will receive an equity investment and could potentially treatment of chronic pain. The goal of the collaboration is to ac- receive development, regulatory and commercial milestone com- celerate Purdue’s Nav1.7 sodium ion channel drug candidates uti- pensation worth up to $790m. lizing AnaBios’ Phase-X discovery platform. Under the terms of this AST-005 is an investigational, topically-applied SNA that targets agreement, Purdue will license to AnaBios the rights to a suite of tumor necrosis factor, a pro-inflammatory cytokine shown to be a patents for its Nav1.7 sodium ion channel blockers. AnaBios will key mediator of psoriasis. In a recently completed Phase I trial, 15 use its Phase-X technology to de-risk the assets and select a clini- patient volunteers with chronic plaque psoriasis were treated with cal candidate. The two companies will also form a joint steering AST-005 for 10 days. This study met the safety and tolerability re- committee to manage preclinical as well as clinical development quirements in patients with mild to moderate psoriasis. In addition of the lead molecule. to the safety data collected in the Phase I study, pharmacodynamic AnaBios’ Phase-X technology enables the investigation of hu- assessments were performed from the treated plaque area. man drug responses in the preclinical stage of drug discovery. It Psoriasis may seem like an odd move for Purdue, which is tra- is focused on the preservation of human sample viability as well ditionally a developer of pain therapies. Alan Butcher, head of li- as advanced in vitro interrogation methods for obtaining human- censing and business development at , said: “Our relevant data on drug activity. long-term, strategic collaboration agreement with Exicure fits Published online 13 December 2016 Purdue’s short- and long-term development strategy to identify cutting edge platforms that allow us to develop novel medi- Purdue CEO outlines plans for growth away from opioid market here: cines to address unmet medical needs across multiple thera- http://bit.ly/2i6ofKi peutic areas.”

scrip.pharmamedtechbi.com 23 December 2016 | Scrip intelligence | 7 HEADLINE NEWS

CONTINUED FROM PAGE 3 may face special risks are around Trump’s CONTINUED FROM COVER of the risks of government involvement in signature issues of immigration and trade. and anticipates a rapid approval, since there healthcare purchasing – and is certainly no The pharma industry relies on both, and the are no treatments for the devastating disease. fan of the fees that helped fund the coverage incoming president has expressed, shall we The company’s other late-stage pipeline expansion – strengthening the relative hand say, some deep skepticism about them. Un- hopeful is aducanumab for Alzheimer’s dis- of insurance companies to set coverage poli- documented workers aren’t key to pharma’s ease, an exciting and potentially lucrative cies, as many replace proposals would do, is business planning, but many of the propos- – but high-risk – opportunity. Phase III data not something sponsors want to see either. als being developed by the administration are not expected until 2019 or 2020. It’s still too early to see how the health would even eliminate visas for highly skilled Vounatsos acknowledged the pipeline insurance reform debate will play out, but workers, meaning that companies might gap between early and late-stage R&D pro- it seems safe to say that the exchanges will not be able to recruit, or even just relocate, grams as a high priority to correct. “We are have been eliminated in one fashion or an- executives and scientists as needed. obviously interested to bolster the pipeline other by the mid-term elections. What ris- On trade, pharma long ago transitioned at all stages with high-quality projects,” he said. “The team is already working on that.” es in their place – and what Medicaid will much of its product manufacturing over- Scangos earned a lot of respect from eventually look like – remains hard to say, seas, and any successful effort by Trump to Biogen investors, transitioning the com- which means companies will be forced Bring Jobs Back through tariffs would be pany into an innovative biopharma focused to manage their pipelines and price their incredibly disruptive. It’s uncertain how on neurology after taking the CEO post in products without a clear sense of who much Trump could even accomplish on July 2010. He oversaw the hugely success- their customers are going to be and how that front, though, given that his position ful launch of the oral multiple sclerosis they will pay for their prescriptions. is an outlier within the Republican party, drug Tecfidera (dimethyl fumarate), but the and building bridges to anti-trade Demo- growth eventually plateaued. CHANGES AT FDA crats might make accomplishing other Biogen’s pipeline also experienced several In the face of all that uncertainly, FDA parts of his agenda more complicated. setbacks. The company’s stock dropped con- could end up being seen as a bastion of When it comes to the status of jobs in siderably as investors grew nervous about calm predictability by comparison. Spon- the US at risk of moving overseas, pharma the high-risk nature of developing drugs in sors may not always like what they hear, should pay careful attention to the situation neurology. Scangos had more research ex- but the applications move smoothly with the Carrier factory in Indiana. The com- perience than commercial experience, hav- through, even if the agency is well off last pany had earlier announced plans to relo- ing previously served as the CEO of the bio- year’s record-setting pace for approvals. cate production to Mexico, and the decision tech Exelixis Inc., so Vounatsos is a departure FDA will of course change in many ways had been a focus of Trump’s campaign. He’s from that entrenched research background. during the Trump administration. Indeed, going to be president now, and the com- Analysts viewed the appointment as a the sixth iteration of the user fee agree- pany has changed its mind. It’s unclear what comfortable fit if not exciting. “We would de- ment, and the 21st Century Cures Act are motivated the switch – financial or regula- scribe him as a safe choice for the CEO seat, already poised to push the agency towards tory concessions from the state, perhaps, but many investors were looking for more of greater use of patient-reported data and or potentially a decision by the defense- a ‘deal-oriented’ CEO or an external executive post-market evidence. contracting parent company to encourage who has already been in a CEO role,” Barclay’s On top of that will be all the changes that good relations with the incoming head of analyst Geoff Meacham said in a note. Trump appointees will make. For example, state. The terms of the arrangement will Leerink analyst Geoffrey Porges said inves- FDA has been uncomfortable, to put it probably become clear eventually. tors are unlikely to view the appointment mildly, with the idea of allowing sponsors Does that mean that pharma firms con- as a great source of near-term upside or more latitude on off-label communications. templating moving research or produc- improved strategic decision making, given One can expect that attitude to change tion overseas should try to cut a deal with Vounatsos’ strictly commercial background. quickly in the new administration. Trump to keep the jobs in the states? If it However, he noted that a sale of the com- But the downside of changes like that, would allow the administration the oppor- pany could still be on the table. “An $80bn+ and even just an increase in the rhetoric tunity for a good public relations moment, transaction is always a low probability and calling for FDA reform, is that the agency it could be worth a try. remains so in our view; nevertheless, the op- staff itself may begin to feel disheartened. But any firms undertaking that strategy portunity in Biogen for an acquirer remains Time spent on internal policy fights is time should realize they are playing with bright, real, and with the scarcity of assets in the in- that can’t be spent advising sponsors, and orange fire. For firms that don’t get too dustry, it remains a significant source of op- a staff being constantly told it needs to close to the flame, however, its basic Re- tion value for Biogen shareholders,” he said. change its approach may in fact not be able publican glow and the fundamentally solid Jeffries analyst Brian Abrahams, how- to maintain the currently strong review. economy the new president will inherit ever, said a sale seems less likely. “We get likely means that industry is looking at a the sense Biogen is likely looking to pursue THE SIGNATURE ISSUES great four years. their path independently and that this an- Those are the kind of risks and benefits Published online 12 December 2016 nouncement reduces the near-term promi- that industry would be facing under any This article is part of Scrip 100’s nence of such a potential event,” he said. Republican president. Where companies Futurology chapter. Published online 20 December 2016

8 | Scrip intelligence | 23 December 2016 © Informa UK Ltd 2016 HEADLINE NEWS

Sanifit Utilizes Calcium Phosphate Pfizer’s Eucrisa Approval By FDA Chemistry To Treat Rare Renal Disease Adds New LUCIE ELLIS [email protected] Dermatology Emerging company profile: Sanifit Labo- antioxidant which works in a similar way to ratories, founded in 2007 as a spin-off Sanifit’s drug by increasing the solubility of Anchor from the University of the Balearic Is- calcium deposits, has been used off-label to Pfizer’s Eucrisa is one of the first new drugs lands, believes it has discovered a new treat calciphylaxis. According to Informa Phar- to launch for the treatment of atopic dermati- approach to treating calcification disor- ma Intelligence’s BioMedTracker database, tis in more than a decade. The launch reflects ders based on compounds that contain there are no other trials ongoing specifically an expansion strategy by Pfizer to move into hexasodium phytate, which inhibits the targeting calciphylaxis. However, clinicaltrials. a new therapeutic area – dermatology. formation and growth of calcium phos- gov does list a handful of studies for products Pfizer Inc. will launchEucrisa phate microcrystals in soft tissue. treating some symptoms of calciphylaxis. (crisaborole) in January as the first Sanifit’s CEO and co-founder, Dr. Joan Per- new drug for atopic dermatitis in anifit Laboratories, a small biotech ello, told Scrip that other drug developers more than a decade and as the first with offices in Palma and San Diego, active in this area are targeting the classical prong in a strategy to expand into Swants to apply 1960s calcification risk factors related to cardiovascular disease, dermatology, a new therapeutic area chemistry to heart disease conditions in re- such as hypertension, but Sanifit is target- for the big pharma. Pfizer announced nal failure patients. ing the calcium phosphate build-up in ar- the FDA approval of the topical non- To date, Sanifit has raised over €40m equity teries. “There are some products to control steroidal phosphodiesterase-4 (PDE-4) to progress development of its lead product, calcium in the blood and others to control inhibitor Dec. 14 for the treatment of SNF472, in cardiovascular disease in end- phosphate but no one else is targeting the mild-to-moderate atopic dermatitis in stage renal failure patients and in the rare crystals that develop in the arteries,” Perello patients two and older. disease calciphylaxis. The company is backed said. “Our target is an organic solid stone. Eucrisa is the first of several new by several international investors including The chemistry around our product was de- drugs on the horizon to treat atopic Caixa Capital Risc, MGA Business Consulting, veloped in the ‘60s but it has not yet been dermatitis, a chronic rash that falls un- Health Equity, YSIOS Capital, Forbion Capital successfully applied to medicine.” der the eczema umbrella but which can Partners, Gilde Healthcare and Edmond de From 2009 to 2013 Perello pioneered be severe. Rivals Sanofi and Regeneron Rothschild; as well as two pharma venture the international development of Sanifit’s Pharmaceuticals Inc. are awaiting FDA groups, Baxter Ventures and Lundbeck Fund. lead candidate from academia to its clinical approval of the first systemic treatment evaluation and SNF472 entered Phase II for for atopic dermatitis, Dupixent (dupli- SANIFIT’S PIPELINE calciphylaxis in Oct. this year. This trial marks mumab), a biologic pending at FDA SNF472 is an experimental drug for the the first clinical investigation of the drug in with a user fee date of March 29. treatment of cardiovascular diseases linked patients with newly diagnosed calciphy- Eucrisa will have the likely advantage of being more affordable than Dupix- to calcification in the end-stage renal dis- laxis. Sanifit expects top-line data from this ent because it’s a topical product, not ease population undergoing haemodialy- study in the second half of 2017. a biologic. Pfizer said Eucrisa will be sis. The drug, which contains hexasodium Meanwhile, for the larger of the two indi- priced at a wholesale acquisition cost phytate, works by stopping the progression cations Sanifit is targeting with SNF472, car- of $580 for a 60g tube, and it plans to of, and reducing, calcification in patients to diovascular calcification related to end-stage offer patient assistance programs. reduce the risk of cardiovascular events. renal disease, a Phase IIb program has been The timely approval – several weeks Sanifit is targeting two indications for approved by regulators and is due to start en- ahead of the Jan. 7 action date – is some SNF472 within the renal failure setting: car- rolling patients soon. Sanifit expects to enroll validation for Pfizer, which acquired diovascular diseases linked to calcification around 400 patients in this Phase IIb study, the drug with the $5.2bn acquisition of and calciphylaxis, or calcific uremic arte- which will have clinical sites in four European Anacor Pharmaceuticals Inc. The com- riolopathy, which is a syndrome of vascular countries and the US. Sanifit estimates that pany said at the time of the acquisition calcification, thrombosis and skin necrosis. there are approximately 2.5 million dialysis pa- that it believes the drug could reach There are currently no approved pharma- tients worldwide with no effective treatment peak sales of $2bn. ceuticals for either of these indications. for this medical condition. To date SNF472 has Calciphylaxis, an orphan disease, is seen completed more than 20 preclinical studies [email protected], 14 Dec. 2016 mostly in patients with stage 5 chronic kidney and was safe and tolerable in a Phase I clinical disease but can occur in the absence of renal trial in healthy volunteers and CLICK failure. The current standard of care includes patients after one month of exposure. Read full story at: both medical and surgical interventions. Published online 14 December 2016 http://bit.ly/2hM3wPx However, intravenous sodium thiosulfate, an Brought to you from the editors of Start Up.

scrip.pharmamedtechbi.com 23 December 2016 | Scrip intelligence | 9 BUSINESS BULLETIN

Alexion Hunts For A CEO While Investors Await Novartis Adds To Dermatology Portfolio Investigation Details Novartis has acquired UK-based dermatology company Ziarco Group Ltd. – a business started in 2012 as a spinout from Pfizer after the big pharma closed Inc. has turned its Sandwich research site in the country – for its Phase IIb atopic dermati- to board director and former AstraZen- tis (eczema) therapy. The company told Scrip that atopic dermatitis is one eca PLC CEO David Brennan to lead the of the “leading priority areas for Novartis to expand its dermatology lead- company through an unexpected transi- ership” beyond well-performing drugs Cosentyx (secukinumab), which is ap- tion. Brennan will succeed David Hallal, proved for psoriasis, and Xolair (omalizumab), approved for chronic sponta- effective immediately, in a leadership neous urticaria. Financial terms of the deal were not announced but Novartis shakeup coinciding with an ongoing au- said, “This is a typical early pipeline bolt-on deal.” The company added that dit investigation, though the company the financial details “are not material to Novartis.” Ziarco’s lead product is said it was due to “personal reasons.”The ZPL-389, a small molecule, selective histamine H4 receptor antagonist, suit- company announced the appointment able for once daily oral administration. The product has completed Phase IIa Dec. 12, along with news that Chief Fi- studies and Ziarco launched a Phase IIb trial in eczema patients in the second nancial Officer Vikas Sinha has also left half of 2016. A Phase IIa psoriasis study for the drug is also due to complete the company “to pursue other opportu- in 2017. In the previously reported Phase IIa eczema study, ZPL-389 reduced nities.” The longtime CFO, who has held EASI (Eczema Area and Severity Index) by 50% at week eight (placebo: 27%, the post since 2005, will be replaced by [p=0.01]). ZPL389 was found to be well tolerated with a safety profile compa- former Honeywell CFO David Anderson rable to placebo. Ziarco’s pipeline also includes ZPL-521, a potent inhibitor immediately. Alexion’s stock opened 10% of cPLA2a, which is at a slightly earlier stage of development for eczema. ZPL- lower at $118.61 and dropped further 521 is expected to complete Phase I/IIa studies in the first half of 2017. to close the day at $115.08, nearly 13% [email protected], 16 Dec. 2016 lower. The leadership changes raise ques- tions about what Alexion might have un- covered in the investigation, which was announced Nov. 9. At the time, the com- generic injectables segment and also ends vestment and already has the in-house pany said it was looking into allegations long-running speculation around an im- technology and expertise to make this by a former employee related to the com- minent sale of Claris’ injectables busi- happen. The major Japanese firm took pany’s sales of blockbuster rare disease ness. Several suitors including private a big step forward in its ambitions in drug Soliris (eculizumab), which resulted equity firms and the local player, Zydus April this year, when it hired Dr. An- in the company delaying its third quar- Cadila, are believed to have examined the toine Yver away from AstraZeneca ter 10-Q filing. Soliris generated sales of assets on the block over the recent past. PLC, where the French national was $729m in the third quarter, growth of Baxter expects the deal to add a global head of oncology for global medicines 9.6%. During a Dec. 12 conference call portfolio of sterile injectables, backed by development. Yver, now global head, with investors, Brennan said the ongo- manufacturing capabilities and a robust Oncology R&D in the newly estab- ing investigation is nearing completion pipeline to follow. Claris Injectables’ mar- lished Daiichi Sankyo Cancer Enter- and the firm has not identified any facts keted portfolio of generic injectables in- prise, told the Tokyo meeting that he to date that would require the company cludes 11 molecules currently approved joined his new employers “due to the in the US along with fully integrated to update previously reported historical quality of the science.” Daiichi Sankyo R&D expertise and three manufacturing results. Alexion expects to file the delayed had already laid out its strategic plans facilities registered with global regulatory 10-Q in January or earlier, he said. for the sector earlier this year, when it agencies, including the US FDA. [email protected], 12 Dec. 2016 said as part of a new five-year business [email protected], 16 Dec. 2016 plan that it was aiming to build oncol- ogy sales to at least JPY40bn ($340m) Baxter Injects $625m In in fiscal 2020 (ending March 2021), Daiichi Sankyo Lays Out and to around JPY300bn by the end ‘Foundational Asset’ Claris Priorities As It Pursues of fiscal 2025. Growth in new therapy Deal street swung back into action in Oncology Ambitions areas where the company has not tra- India ahead of the holiday season with ditionally had a presence is becoming Baxter International Inc. acquiring Cla- Daiichi Sankyo Co. Ltd. has made clear ever more business-critical amid the ris Lifesciences Ltd.’s injectables arm, its intention of becoming a major play- first patent expires this year for its Claris Injectables Ltd, for about $625m. er in the oncology sector, declaring at long-time global top seller, the antihy- The transaction fast-tracks the US firm’s a recent R&D Day that it is committed pertensive olmesartan. quest to emerge as a global leader in the to making the necessary sustained in- [email protected], 15 Dec. 2016

10 | Scrip intelligence | 23 December 2016 © Informa UK Ltd 2016 HEADLINE NEWS

Lilly’s Insulin Discounts Target Hanmi Toughens Controls As High-Deductible Insurance Gaps Employees JESSICA MERRILL [email protected] Arrested For Lilly unveiled a new discount program for et costs. “Our net pricing hasn’t changed its insulins, including Humalog, Humulin in seven years. It’s gone down slightly,” he Insider Trading and Basaglar, that will reduce costs for said. “The patient hasn’t seen any of that.” Prosecutors’ two-month probe into Hanmi people who pay full retail prices. The new discount program, announced Pharmaceutical has concluded without a big Dec. 13 in partnership with Express bang after they found the South Korean firm li Lilly & Co. will introduce a new dis- Scripts Holding Co., could save people did not intentionally delay the disclosure count program for insulins beginning who pay full price for Lilly’s insulins 40%, of a licensee decision to end a cancer drug EJan. 1 that will offer assistance to peo- the firm said. The start of the program will partnership, but several employees have ple who pay full retail prices at the pharma- coincide with the initiation of a new de- nevertheless been arrested over improper cy, including those who have no insurance ductible period for most health plans on information leakage. or are in high-deductible plans. Jan. 1 and it will be available for Huma- South Korean prosecutors have “Changes in insurance benefit design log (insulin lispro), Humulin U100 (insulin arrested four employees of Hanmi Sci- have increased the cost of insulin for human injection) and Basaglar (insulin ence, the holding company of South some people,” Lilly acknowledged in a glargine), a follow-on version of Sanofi’s Korea’s Hanmi Pharmaceutical Co. statement. “While discounts and rebates blockbuster long-acting insulin glargine Ltd., on charges of leaking undisclosed paid by manufacturers make insulin af- Lantus. Basaglar was approved last year, information and making illegal stock fordable for most people, they don’t di- but just launched this month under a pat- trading profits using the information. rectly help with the uninsured or people ent agreement with Sanofi. Two others were indicted without in the deductible phase of their high- People who want to take advantage of detention, while 11 were summarily in- deductible insurance plan.” the new discount will need to go outside dicted in the investigation. A total of 45 The rise of high-deductible plans is their health plan to a mobile and web- people, including retail investors, were one factor that has contributed to the based platform by Blink Health to get found to have taken illegal stock trad- public’s growing concern about drug the savings. One downside for patients ing profits or prevented losses using the pricing. High out-of-pocket costs fueled is that the price may not be applied to leaked information, of which fines will the public fury over the $600 price of annual deductibles. Thus, patients may be imposed on 25. NV’s emergency allergy medicine want to compare benefits and decide However, prosecutors concluded that EpiPen (epinephrine) earlier this year. which program is best for them, Lilly said. Hanmi Pharmaceutical’s owner and Price increases have played a role, but The price Blink will discount Basaglar family members, as well as company the drug industry increasingly has been from is $337.11, while the Humalog 10mL officials handling disclosures, did not pointing the finger at high-deductible in- vial price Blink will discount from is $272.32 intentionally delay disclosing a deci- sion by GMBH surance plans, which make patients front and Humulin N KwikPen is $462.85, accord- to cull a lung cancer partnership with the full cost of drugs until their deductible ing to Lilly. Humalog and Humulin come in the company. has been paid, which means they take numerous formulations and prices. In July 2015, Boehringer and Hanmi notice. Lilly estimates that about 10% of People can order their prescriptions inked an exclusive license and collabo- people in the US are on a high-deductible from Blink Health and pick up their pre- ration agreement for the development plan and about 1% are uninsured. scriptions at almost any US pharmacy, and global commercialization rights, Mylan CEO Heather Bresch, during an including , CVS, Target, RiteAid, except , China and Hong appearance at the Forbes Healthcare Safeway and Kroger, the company said. Kong, for , a novel third gen- Summit Dec. 1, defended her company’s Prescriptions reimbursed under a gov- eration, EGFR-targeted therapy for the decision to raise the price of EpiPen from ernment program are not eligible. treatment of EGFR mutation-positive $100 over an eight-year period, but said Lilly and Express Scripts have been ex- lung cancer. the company failed to understand the ploring options for patients who pay full But this October, prosecutors raided changing insurance dynamics. retail price since the fall, and the pharma the headquarters of Hanmi amid suspi- Lilly’s incoming CEO David Ricks also said it has met with advocacy groups and cions leakage of undisclosed informa- attended the conference and was asked patients to talk about their concerns. tion on Boehringer’s decision. about the cost of insulins, a category of “We’re committed to seeking addi- medicines that have also come under fire tional solutions so that everyone who [email protected], 14 Dec. 2016 for price increases. He attributed the issue uses insulin has reasonable access,” Lilly to the high rebates Lilly negotiates with added. Read full story at: http://bit.ly/2i6yX3r payers for its insulins and high out-of-pock- Published online 13 December 2016

scrip.pharmamedtechbi.com 23 December 2016 | Scrip intelligence | 11 HEADLINE NEWS

The Competition Begins To Host The Post-Brexit EMA

Denmark, France, Ireland, Italy, Spain and 2017 EMA Host SWEDEN have all have expressed a Choices keen interest in hosting the European Medicines Agency DENMARK once the UK leaves the EU. IRELAND Bids are expected to be made sometime early next year, probably once the UK gov- FRANCE ITALY ernment triggers Article 50.

There is at present no formal SPAIN process for allocating an agency to a particular EU country, as this tends to be Denmark Life sciences: Denmark is home to a number of major pharmaceutical and biotech companies including Novo Nordisk, LEO Pharma and Lund- done via a process of political beck. The country is also part of the Medicon Valley life science alliance wrangling, so each prospec- with Sweden, which includes 12 universities and 32 hospitals. tive candidate will need to Regulatory agency: The Danish Medicines Agency has some 400 garner as much support for employees and is based in Copenhagen. Its director general Thomas Senderovitz said their bid as possible from the in September that the agency was strengthening its leadership and setting up a new medical evaluation and biostatistics division to create a “Danish Medicines Agency in the other member states. European top class.”

Travel and language: Good transport links to other European capitals: one hour by air to Key factors to be taken into Berlin, two hours to London and Paris, a bit longer to Barcelona and Milan. Copenhagen has account when deciding who the largest airport in Scandinavia. Official language Danish, but English widely spoken. should host the EMA include Other agencies: European Environment Agency (Copenhagen). the existing life sciences network in the country, the role and size of the national DenmaFrancerk Life sciences: France has a strong R&D-based pharmaceutical industry. regulatory body, factors like Its life science network includes Paris Biotech Santé (a bioincubator for medicines and medical devices start ups), the Genopole biocluster, and language and accessibility the biotech, health and environment cluster, Biocitech (all in Paris) as well from other EU countries, and as regional hubs like the Lyon Bio Pole and the Eurasante health and whether there is already an biotechnology park in Lille. EU agency established in the Regulator: ANSM is a high-profile and proactive regulator and has a strong representation country. Having an existing at the EMA. agency could militate against a country getting another, Travel and language: France is at the heart of the EU both geographically and politically, and Paris has good links transport to other European cities. Lille and Lyon are also contenders although some argue that to host the EMA because of the regional life science hubs there. Language: French, English there could be synergies if the widely spoken. existing agency worked in an Other agencies: European Securities and Markets Authority (Paris), EU Institute for Security overlapping area such as food Studies (Paris), Community Plant Variety Office (Angers), European Railway Agency (Valenci- or the environment. ennes and Lille).

12 | Scrip intelligence | 23 December 2016 © Informa UK Ltd 2016 HEADLINE NEWS

Ireland Life sciences: Ireland has Regulator: The Health Products Regulatory ties, and easy air connectivity with other a strong presence in phar- Authority (HPRA) has an international reputa- EU cities. Ireland is an “English language maceutical innovation and tion and already works closely with the EMA, location” and English is “the working lan- research. The development with its staff involved in some of the EMA’s guage of the EMA and the pharmaceuti- agency IDA Ireland says committees and working parties. cal industry,” according to the Department nine of the top ten global of Health. pharmaceutical companies have operations Travel and language: The government in the country, and there are collaborative says Dublin is the best location for busi- Other agencies: Eurofound (Dublin), which clusters in pharmaceutical, biotechnol- ness continuity for the EMA because of provides information and advice in the area ogy, medical devices and diagnostics, based its proximity to the UK (some EMA staff of social and work-related policies, particu- mostly in Dublin and Cork but increasingly in currently based in London could perhaps larly living and working conditions and in- Sligo, Waterford and Mayo. commute, for example), cultural similari- dustrial relations.

Italy Life sciences: A strong biopharmaceutical R&D Spain Life sciences: A strong pharmaceutical in- and manufacturing base, as well as the Human dustry, in both R&D and manufacturing, and Technopole life science project and the Alisei clus- a network of almost 80 science and technol- ter for life sciences, both in Milan, northern Italy. ogy parks, research centres and technology The Human Technopole is intended to be a “centre institutes. The industry body Farmaindustria of excellence” in areas like genomics, neurodegen- supports a Spanish location for the EMA. Ma- erative diseases and big data, and is expected to begin construction drid and Barcelona have both expressed interest in hosting the in January 2017 with completion due by 2040. There have been sug- agency. Barcelona is the capital of the region of Catalonia, which gestions that the EMA could be located at the Human Technopole. according to the regional government accounts for almost half of Spain’s pharmaceutical manufacturing output and is home to Regulator: AIFA is a strong player in the EU regulatory network. a number of major domestic companies including Almirall and Guido Rasi, executive director of EMA, is Italian, as are some 12% of Esteve, as well as some major international pharma and biotech the EMA’s permanent staff. companies.

Travel and language: Milan seems to be the leading contender, Regulator: The AEMPS is a well-regarded agency with strong rep- rather than the capital Rome. The city is a high-profile business cen- resentation at the EMA. tre and is also slightly nearer to the geographic centre of the EU than Rome, and transport links to the rest of the EU are good. The Alisei Travel and language: Good air links between Madrid and major Cluster and the Human Technopole are both in Milan. Italian is the of- European cities. Spanish is the official language, although it has a ficial language, although French and German are legally recognized number of regional languages including Catalan, Basque and Gali- in some northern regions. English is widely spoken. cian. English is widely spoken.

Other agencies: The European Food Safety Authority (Parma) and Other agencies: Spain already hosts the EU Intellectual Property the European Training Foundation (Turin). EFSA provides indepen- Office (Alicante), European Agency for Safety and Health at Work (Bil- dent scientific advice on risks associated with foods, and there have bao), European Fisheries Control Agency (Vigo). It could also be a been suggestions that the EMA and EFSA could be merged to form contender for the European Banking Authority, which like the EMA a FDA-style agency. has its headquarters in London.

Sweden Life sciences: Sweden icon Valley life science cluster, a venture Travel and language: The government’s has a strong biophar- shared with eastern Denmark. life science advisor has said that Stockholm maceutical industry, a is a “little bit further away” and there are not network of well-known Regulator: The Medical Products Agency and as many flights as to London. Language is universities (including the UK MHRA currently lead the field in terms Swedish, but English is widely used. the Karolinska), and some of work done on behalf of the EU regulatory private and public R&D institutes like the network, acting as rapporteur for centralized Other agencies: European Centre for Uppsala Clinical Research Center. It also approval applications in about 25% and 30% Disease Prevention and Control (Stock- has an established life science quarter of cases respectively. The government says holm). This might count against Sweden in Stockholm, strengths in IT and mobile the MPA will be the largest national medicines as a location for the EMA, but on the other technology, and a good biologicals manu- agency in the EU once the UK leaves, and that hand there could be synergies between facturing base. Sweden is part of the Med- it would collaborate well with the EMA. the two.

Refs: Commons debate on EMA https://www.theyworkforyou.com/whall/?id=2016-10-12a.115.0&s=speaker%3A25386 scrip.pharmamedtechbi.com 23 December 2016 | Scrip intelligence | 13 HEADLINE NEWS

Bristol Closes, Consolidates R&D Concern Over COPD Update Sites Under Cost-Containment Plan There has been some criticism of the recent The pharma will consolidate some operations in New Jersey, it won’t renew the update to COPD management guidelines lease on a Seattle site acquired with ZymoGenetics deal and intends to close an published by GOLD, with concern over the R&D site in Connecticut as part of a cost-control plan outlined in October. how much of the changes are based on clini- cal evidence. JOSEPH HAAS [email protected] The Global Initiative for Chronic Obstructive Lung Disease (GOLD) re- ristol-Myers Squibb Co. announced a However, Bristol will not renew the lease cently published its first update in five plan to shutter some US research and when it expires in 2019 for the Lake Union years on treatment recommendations Bdevelopment sites as well as not fol- Steam Plant in Seattle that was acquired for COPD. It now favors fixed-dose low through on a planned development and integrated following the 2010 buyout LABA/LAMA combinations over ICS/ site in Connecticut as part of the cost-con- of ZymoGenetics Inc. It also will initiate a LABA combinations. It had previously tainment strategy that CEO Giovanni Cafo- phased, multi-year shutdown of its R&D recommended the use of either a LABA/ rio outlined during the firm’s earnings call plant in Hopewell, NJ, by mid-2020, close LAMA or ICS/LABA in the majority of in October. a site in Wallingford, CT, by the end of 2018 COPD patients. However, not everyone The New York pharma said Dec. 13 that and not build a planned site elsewhere in is convinced of the changes. the consolidation of its R&D facilities will Connecticut. Chiesi Farmaceutici SPA, while ac- strengthen its capabilities by, among other A Bristol spokesperson told Scrip that the knowledging an update was “a positive things, integrating biologics development plans announced Dec. 13 are “aligned with step forward,” has some concerns. with clinical manufacturing to yield greater the transformation of our operating model “The evidence base of the new version of the GOLD report is limited in certain speed and collaboration. But on the Oct. that was announced in the third quarter key areas, since, as clearly written in the 27 third quarter earnings call – during earnings call. We looked at our current US body text, the basis for treatment recom- which Bristol reported 21% year-over-year sites and made decisions to focus resources mendations is only partially from evi- at locations in the heart of vibrant ecosys- growth in global product sales, including dence coming from randomized clinical tems of academia, world-class science, in- 36% growth domestically – Caforio said trials,” said professor Stefano Petruzzelli, the pharma was undertaking “an evolution novation and business opportunities. These chief medical officer and head of global of our operating model” to focus both R&D changes will ensure we have the structural, clinical development for Chiesi. and commercial efforts on activities that of- operational and financial flexibility to deliver Chiesi does not market a combined fer the best potential long-term outcomes as effectively as possible on our mission for LABA/LAMA product. In addition, in for the company. patients. Our decisions will focus our re- September this year, the Italian firm sources, simplify our work and integrate our was the first to file a triple combination efforts based on the needs of our business product in Europe, the ICS/LAMA/ and the size of our company – today and in LABA product CHF 5993. the future.” It is likely that the publication of data Morningstar analyst Damien Conover from Novartis AG’s FLAME study com- said when asked about Bristol’s realignment paring its Ultibro Breezhaler (a LABA/ that it appeared to be adequate to meet the LAMA) with GlaxoSmithKline PLC’s Ad- cost-containment agenda cited by Caforio vair/Seretide (an ICS/LABA) in reducing in October. “The strategy looks consistent COPD exacerbations was a significant with Bristol’s efforts to keep operating costs catalyst in changing the guidelines. flat from 2016 to 2020,” he said. “This cost Chiesi however notes that “this effect control should create strong earnings lever- was not demonstrated in patients with a history of more than one exacerba- Shutterstock: toeytoey Shutterstock: age for the firm.” Bristol noted that the closures occur in tion” and so the recommendation to step up from LAMA to LABA/LAMA “is Bristol now says that it will invest in tandem with other growth of its R&D appa- at least questionable and not supported construction of a new R&D building at its ratus. This includes development of a state- by evidence.” Lawrenceville, NJ, campus, providing a of-the-art research facility in Cambridge, MA, single location for lab-based Discovery and expansion of its Redwood City campus near [email protected], 12 Dec. 2016 Translational Medicine activities. It also will San Francisco and a recently opened Princ- continue construction of a biologics de- eton Pike facility in New Jersey. The company CLICK velopment space at its New Brunswick, NJ, emphasized that its latest moves focus its Read full story at: site and continue expansion of its biologics R&D efforts on three technology hubs. http://bit.ly/2hLC1Df campus in Devens, MA. Published online 13 December 2016

14 | Scrip intelligence | 23 December 2016 © Informa UK Ltd 2016 POLICY & REGULATION BRIEFS

Actavis UK’s ‘Excessive’ Price Hikes Targeted Lilly’s Olumiant To Be EU’s First RA JAK has again fallen foul of the Inhibitor UK Competition and Markets Author- ity, this time for charging the National Eli Lilly & Co.’s Olumiant (baricitinib) is to become the first JAK inhibitor to Health Service “excessive” prices for reach the EU rheumatoid arthritis market after it won a recommendation generic hydrocortisone tablets. The from the European Medicines Agency’s CHMP. Key opinion leaders are im- CMA said on Dec. 16 that Actavis had pressed with the data, but pricing will be paramount for payers, especially raised the price of hydrocortisone 10mg given the availability of biosimilar etanercept, says Datamonitor Healthcare tablets by 12,000% compared with the analyst Christina Vasiliou. The CHMP has recommended that Olumiant be price of the branded version sold by indicated for the treatment of moderate to severe active rheumatoid arthritis another company before April 2008. in adult patients who have responded inadequately to, or who are intolerant The amount the NHS was charged for to, one or more disease‑modifying antirheumatic drugs. It can be used either packs of the product soared from £0.70 as monotherapy or in combination with methotrexate. It is taken daily as an ($0.90) in that month to £88 by March oral tablet. According to Vasiliou, pricing will be very important in terms of 2016. Prices of the 20mg tablets rose uptake. Olumiant will face competition from well-established anti-TNFs such by nearly as much, by almost 9,500%, as AbbVie Inc.’s Humira (adalimumab), and as Vasiliou highlights, ’s equating to an NHS cost of £102.74 per Enbrel (etanercept) now faces biosimilar completion. “Anti-TNFs, either the pack by March this year, compared with reference brands or their biosimilars, are likely to be the preferred first-line the original price of £1.07 for the brand- agents based on formulary placement. Payers may enforce step therapy requir- ed drug. About 943,000 packs of hydro- ing treatment with an anti-TNF before baricitinib can be used,” she says. How- cortisone tablets were dispensed in the ever, she points out that Olumiant showed superiority to Humira and metho- UK in 2015, by which time NHS spend- trexate at the first line in the RA-BEAM and RA-BEGIN studies, respectively. ing on the tablets had risen to £70m a [email protected], 16 Dec. 2016 year, compared with about £522,000 a year before April 2008, the authority said. In a Statement of Objections sent and on Dec. 14 details of the form’s to Actavis, the CMA alleged that the nine observations emerged, with company “broke competition law by analysts terming some “procedural” Will $2.5Bn Jury Verdict charging excessive and unfair prices” in nature and others “critical.” Sun for the tablets, which are used as prima- Against Gilead Stand? Pharma’s share price fell by just 0.5% ry replacement therapy for people with to INR679 ($10) on the same day While a Delaware jury found that adrenal insufficiency, a life-threatening when investors learned of the form’s Inc. willfully in- disease. The authority stressed, though, contents, and analysts said much fringed Merck & Co. Inc.’s hepati- that “no conclusion should be drawn at of the bad news was already in the tis C treatment patent and awarded this stage that there has in fact been any share price following the announce- Merck a whopping $2.54bn, the final breach of competition law.” ment a week ago that the notifica- payout is uncertain. Gilead is appeal- [email protected], 16 Dec. 2016 tion had been issued. That sent the ing the verdict to the US Court of Ap- shares down by 6% at the time. The peals for the Federal Circuit and the Analysts Cut Sun Forecasts FDA report said inspectors had un- company is expected to ask Delaware covered inadequate testing methods District Court Judge Leonard Stark to After New Halol Site Faults and laboratory controls, lax adher- set it aside. The jury awarded damages Another US regulatory rap on the ence to standard operating proce- based on a 10% royalty rate of Gilead’s knuckles for Halol, the biggest Indian dures and a range of other problems. US sales of Sovaldi (sofosbuvir) and plant of Sun Pharmaceutical Indus- “Testing programs are not adequate- adjusted sales of Harvoni (sofosbu- tries Ltd., over perceived violations ly designed,” FDA inspectors Patric vir/ledipasvir) through August 2016, of good manufacturing practices Klotzbuecher and Santos Camara which totaled $25.4bn. Judge Stark was the last thing financial markets observed in the 14-page document. will determine if Gilead must pay roy- anticipated after the company’s year- The inspectors added the “establish- alties on future sales and, if so, the long remediation efforts. Instead of ment of test procedures…(is) not ad- royalty rate. He will also determine delivering the all-clear following a re- equately reviewed and approved” and the penalty for willful infringement, cent inspection of the site, the FDA as such “the accuracy of test methods which can be up to three times the instead issued a new Form 483 listing has not been established.” damages award. potential violations of US standards, Penelope MacRae, 15 Dec. 2016 [email protected], 16 Dec. 2016 scrip.pharmamedtechbi.com 23 December 2016 | Scrip intelligence | 15 EXPERT VIEW

Brexit: What Can The Life Sciences Industry Do About It? With the UK seemingly heading towards an exit from the European Union in just two and a half years’ time, restrictions on the free movement of people, products and finance will impact the life science sector as much as, if not more than, many others. IAN SCHOFIELD [email protected]

rexit means that access to research about curbing the free movement of EU departs the EU. The report identified four networks and funding could be im- citizens into the UK, and the EU sticks by its priority areas: Bpaired, and the mobility of scientists, insistence that the “four freedoms” are indivis- • The ability to trade and move goods and researchers and company staff limited. ible, the result is likely to be some sort of “hard capital across borders. Industry wants Moreover, the relocation of the European Brexit” with all that entails in terms of trade, free trade with the EU to continue, ide- Medicines Agency will bring its own staffing legislation, regulation, migration and so on. ally on the same terms as a full member and recruitment problems, and the possibil- In the meantime, life science businesses of the customs union and the common ity of regulatory divergences between the are left wondering: should we invest in the EU VAT system, with no tariff or non-tariff UK and the EU threatens to delay new drug UK, wait, or decide now to go somewhere barriers such as inspections and import/ approvals and clinical trials. else to avoid the continuing uncertainty? export declarations, which the report said would cause “significant disruption and increased costs.” • Ensuring long-term, predictable fund- ing for scientific research, and continued ability to collaborate at scale. The group wants to convince ministers of the need for continued long-term access to EU funding and collaboration programs, particularly Horizon 2020, possibly through associate member status. • Access to the best talent: unrestricted movement of researchers and industry staff would be key to maintaining access to the best scientific talent in the UK. • The need for a unique cooperation agreement on the regulation of medi- cines in Europe. This last point is probably the area of most immediate concern to industry. Theresa May Brexit means the EMA will have to relocate Shutterstock: Charlie Bard Charlie Shutterstock: out of the UK, with all that means for its staff and its experts, not to mention the While the life science sector is well ac- LIFE SCIENCES STEERING input from the UK’s Medicines and Health- customed to adapting to rapidly changing GROUP care products Regulatory Agency, which circumstances, the upheavals and uncer- In an attempt to come up with some an- has been the lead or co-lead regulator for tainties brought by Brexit are so funda- swers in the wake of the vote, the biophar- a quarter of the 900-plus medicines ap- mental and wide-reaching that it is difficult maceutical industry and the government proved through the EU centralized proce- to know how best to mitigate the effects of set up a “UK EU Life Sciences Transition dure so far. these changes and make the most of any Programme” led by the UK EU Life Sciences Following Brexit, EU drug approvals opportunities that might arise. Steering Group, a joint industry-govern- would no longer be automatically valid in The problem is that no one yet knows ment task force co-headed by Andrew Witty, the UK, while EU incentives like regulatory what kind of relationship the UK govern- Pascal Soriot and Neil Mesher, respectively data protection and orphan drug rewards ment is planning to negotiate with the CEOs of GlaxoSmithKline PLC, AstraZeneca could be lost and co-operation in pharma- EU after Article 50 is triggered, probably in PLC and Philips Electronics UK. covigilance and other areas impaired. spring 2017, and this makes it very difficult On Sept. 6, the group presented a re- Some fear the country would as a result to plan ahead. port to ministers outlining the key issues become a “second priority” launch market Prime minister Theresa May insists she is facing the sector as well as a range of op- that was less attractive to investments in seeking the “best possible deal” for the UK in tions for preserving the competitiveness drug development and manufacture, par- its relations with Europe, but if she is adamant of the life science sector once the UK ticularly if the UK chose not to implement

16 | Scrip intelligence | 23 December 2016 © Informa UK Ltd 2016 EXPERT VIEW

the provisions of the new EU Clinical Trial There is also anxiety over aspects of re- And in his autumn statement, Chan- Regulation with its streamlined trial ap- cruitment to life science firms. Novasecta cellor Philip Hammond announced mea- proval system, which is due to come into cited some CEOs as saying that several sures for funding and promoting R&D effect in 2018. senior level people had decided not to and innovation, including additional It is clearly in the interests of the life sci- apply to work in their companies. The R&D spending via a new National Pro- ences industry to stress the importance “uncertainty and risk of the UK as a po- ductivity Investment Fund, a review of of keeping regulations aligned as far as tential non-EU country is adding a nega- the R&D tax credit and a patient capital possible, and industry has made much of tive weighting to business cases that in- review intended to tackle obstacles to the need for some sort of regulatory co- volve investing in it,” it commented. “The getting long-term investment into inno- operation agreement where the UK could whole talent pool and system of MHRA, vative firms. The BIA said it was “fantastic continue to play a part in future EU policy, EMA and clinical trials in the UK requires to see this government showing an un- guidance and legislation, including EU ap- a strong network, close relationships and derstanding of what is important to life proval procedures and pharmacovigilance a hub location. Our research reveals that science companies.” systems. executives do not view the UK as favor- But the government is sending out ably as they used to.” WHAT MORE CAN BE DONE? mixed messages about how far it is pre- Moreover, Brexit is taking up a great But with the cloud of uncertainty still hang- pared to go to protect the interests of the deal of companies’ time and resources, ing over the sector, what more can the in- life sciences sector. The prime minister may and is a huge distraction from the day to dustry do to shore up its future prospects as have said she considers it of great strate- day business of building up companies a non-EU country? gic importance to the country, but it’s not and will remain so for many years, accord- As part of an ongoing process, the life clear how far ministers were impressed ing to Harren Jhoti, CEO of Astex Pharma- sciences steering group held its second by the concerns outlined in the steering ceuticals Inc. meeting on Nov. 23. Little has been re- group’s report. “We also need to remind ourselves that vealed publicly about what was discussed And while David Davis, secretary of state we are working in a ferociously competi- although it seems that industry is taking for exiting the EU, has said recently that tive sector,” Jhoti said at the round table dis- a two-pronged approach in its talks with regulation is “one of the things that we will cussion. “So while the executives running ministers. seek to get standardized,” his colleague, the companies are distracted by this huge One is to highlight the specific Brexit- international trade secretary Liam Fox, ap- issue, they’re not building the company. related impacts on the sector – regulatory, pears to be of the opposite view. All our competitors around the world are trade, people and so on – in an attempt to In any case, even if the government did building their companies. There’s no an- ensure that the future UK-EU relationship support a regulatory cooperation agree- swer to that, it is what it is, but we all know provides a stable environment allowing ment in principle, this would still have to the EU doesn’t move very fast.” timely access to innovative medicines in be negotiated with the rest of the EU, with Novasecta also found some executives the UK, mobility of staff between the UK the outcome far from certain. were concerned that the EU itself would and the EU, and so on. So life science firms are understandably “become weakened as a pharmaceuti- The other aim is to build on the finan- uneasy about what the future holds, and cal hub compared with an increase in cial and R&D support promised by the there are signs that the uncertainty is al- the strength of the US and Asia.” One said prime minister and the Chancellor in ready making the UK look less attractive as that an Asian company had postponed its November as the first steps in a “modern, a place to invest in the longer term. planned European entry because of the ambitious Industrial Strategy,” and to en- Brexit vote. sure that the strategy is conceived in such HOLDING OFF ON DECISIONS Of course, Brexit may also give rise to a way as to strengthen the UK life science Recent research by pharma strategy con- new opportunities, and industry is doing sector and make it better able to face the sultancy Novasecta found, for example, its best not to paint too bleak a picture. challenges ahead, whatever happens on that many firms are holding off on key As the BioIndustry Association pointed the Brexit front. decisions in areas like R&D (particularly out in a Nov. 21 discussion document, the It is understood the government will clinical research), manufacturing and the upsides could include greater freedom to now release the Industrial Strategy in early supply chain. design innovation-friendly regulations in 2017, and will then invite the various in- Similar concerns were expressed at a areas such as genetic modification and dustry sectors to comment on it before round table organized by Scrip and Price- cell-based therapies, and better targeting the next Budget, which is expected to take waterhouseCoopers in September. Jo of tax incentives to key industry sectors. place in March or April 2017 – around the Pisani, partner in the UK pharma and life There was another ray of optimism when time that the prime minister has said she sciences consulting practice at PwC, said: the government said on Nov. 28 that it expects to trigger Article 50 and begin ne- “Unfortunately, we have seen some foreign plans to ratify the agreement on Europe’s gotiations over the future relationship of direct investment decisions being reversed future Unified Patent Court after all, al- the UK and the EU. It looks like spring 2017 at the last minute; we’ve seen some col- though this was tinged with doubts as to will be an interesting time in more ways laboration agreements being dismantled, whether the UK could stay in the new pat- than one. and clinical trials locations changed.” ent system post-Brexit. Published online 12 December 2016 scrip.pharmamedtechbi.com 23 December 2016 | Scrip intelligence | 17 R&D BITES

Express Scripts Adds Gilead’s Harvoni To 2017 Formularies Eisai’s Cancer Strategy Bears Fruit After making headlines with formulary Early data from an open-label, single-arm, multicentre Phase Ib/II study in- placement in 2015 that excluded Gile- vestigating the combination of Eisai Inc.’s Halaven (eribulin) with Merck & ad Sciences Inc.’s products, Co. Inc.’s Keytruda (pembrolizumab) in 106 patients with metastatic breast Express Scripts Holding Co. revealed cancer who had previously been treated with up to two lines of chemo- Dec. 12 that it will include the fixed- therapy showed an overall response rate of 33.3% in the 39 patients evalu- dose combination pill, Harvoni, on its able so far. One patient had a complete response and 12 patients a partial national preferred formulary for 2017. response. The overall response rate was also similar between both PD-L1 The pharmacy benefit manager also positive and negative cohorts. Eribulin is the first in the halichondrin class announced that its indication-based of microtubule dynamics inhibitors and is approved in the EU and US for oncology management program is ex- locally advanced or metastatic breast cancer which has progressed after at panding next year, including the addi- least one chemotherapeutic regimen for advanced disease, as well as for use tion of multiple myeloma among the in liposarcoma and soft tissue sarcoma. Keytruda is available for NSCLC covered indications. Express Scripts and melanoma and is in Phase II development for use as a single agent in said the success of its Hepatitis Cure metastatic triple negative breast cancer. Study researcher Dr Sara Tolaney Value Program, which has leveraged a of the Dana-Farber Cancer Institute in Boston explained the rationale be- discount agreement with AbbVie Inc. hind the combination: in preclinical and translational studies, eribulin in- and provided exclusive formulary po- duced tumor vascular remodeling, reduction of hypoxia and promotion of sition for Viekira Pak in treating geno- the less aggressive epithelial phenotype in advanced breast cancer tumor type 1 HCV patients over the past two tissue, she said. “We hypothesised that these effects of eribulin on tumour years, has now enabled it to negotiate biology and microenvironment may increase the drug delivery of immune better pricing for Harvoni (sofosbuvir/ checkpoint inhibitor, pembrolizumab, in metastatic triple negative breast ledipasvir). As a result, Harvoni and cancer and further enhance the possibility that pembrolizumab would en- Viekira (dasabuvir, ombitasvir, pari- able the immune system’s T cells to detect and attack tumor cells.” taprevir and ritonavir) both will be [email protected], 13 Dec. 2016 listed as preferred products on its for- mulary in 2017. Express Scripts says this will expand treatment options for physicians while maintaining an HCV of the Phase IV PLATO study. A posi- cost-of-treatment reduction of nearly tive readout would have been good 50% compared to list prices. news for prostate cancer patients and Zykadia Challenged As [email protected], 14 Dec. 2016 Pfizer, which needs to expand sales of Roche’s Alecensa Gets EU Nod Xtandi to justify the $14bn price it paid to acquire Medivation Inc. ear- Roche’s anaplastic lymphoma kinase- Xtandi/Zytiga Study Fails lier this year. Nonetheless, the chal- positive (ALK+) advanced non-small cell lenge of showing a benefit in patients lung cancer (NSCLC) therapy, Alecensa A combination of the two market- already treated with Xtandi was sub- (alectinib), has been given the green leading androgen receptor inhibitors stantial. Pfizer and Astellas still have light for approval in Europe as a second- together failed to show a benefit in other opportunities to expand Xtan- line treatment. The European Medi- already-treated prostate cancer pa- di’s indications. The companies are cines Agency’s scientific committee, the tients. Pfizer Inc./Astellas Pharma CHMP, has given the drug a positive rec- Inc.’s androgen receptor signaling studying Xtandi in other combina- ommendation in its December round of inhibitor Xtandi (enzalutamide) in tions in prostate cancer and in other combination with Johnson & John- tumor types, including breast cancer. assessments, citing its activity in ALK+ son’s androgen biosynthesis inhibitor In October, FDA approved a sNDA to NSCLC patients previously treated with Zytiga (abiraterone acetate) plus pred- update labelling for Xtandi to include Pfizer Inc.’s Xalkori (crizotinib) as a key nisone did not improve progression- new clinical data versus bicalutamide benefit of Alecensa. Pfizer’s NSCLC free survival over Zytiga/prednisone (Casodex and generics) from the TER- therapy, a multi-targeted tyrosine ki- alone in patients with chemotherapy- RAIN study, showing Xtandi reduced nase inhibitor, was approved in 2011. naïve metastatic castration-resistant the risk of radiographic progression The CHMP’s recommendation is based prostate cancer (CRPC) whose pros- or death by 40% compared to bicaluta- on two Phase II studies, in which Ale- tate-specific antigen (PSA) has previ- mide, and a median radiographic PFS censa showed objective response rates of ously progressed following treatment of 19.5 months versus 13.4 months. 50.8% and 52.2%. with Xtandi, according to the results [email protected], 15 Dec. 2016 [email protected], 16 Dec. 2016

18 | Scrip intelligence | 23 December 2016 © Informa UK Ltd 2016 HEADLINE NEWS

Daiichi Sankyo Lays Out Priorities Daiichi Sankyo says it is “committed to a major transformation in oncology” as it prioritizes and pursues projects in this field under a new team leader, who chose to highlight unique antibody-drug conjugate technology and the acute myeloid leukemia franchise at a recent R&D Day in Tokyo. IAN HAYDOCK [email protected]

aiichi Sankyo Co. Ltd. has made clear gy sales to at least JPY40bn ($340m) in fiscal gastric cancer and other HER2-expressing its intention of becoming a major 2020 (ending March 2021), and to around solid cancers. Yver spent time outlining the Dplayer in the oncology sector, declar- JPY300bn by the end of fiscal 2025. unique advantages of the Japan-developed ing at a recent R&D Day that it is committed Growth in new therapy areas where the ADC technology, which compared with to making the necessary sustained invest- company has not traditionally had a pres- standard ADCs roughly doubles the drug to ment and already has the in-house technol- ence is becoming ever more business-criti- antibody ratio (to 7-8), has high linker stabil- ogy and expertise to make this happen. cal amid the first patent expiries this year for ity, and a very short systemic half-life. “The The major Japanese firm took a big step its long-time global top seller, the antihyper- linker is cut by enzymes over-expressed in forward in its ambitions in April this year, tensive olmesartan. the cancer cell lysosome, meaning there is when it hired Dr. Antoine Yver away from no ‘leakage’ in the blood,” he explained. AstraZeneca PLC, where the French national FLAGSHIP ASSET High solubility also means that the ADC was head of oncology for global medicines Yver chose to concentrate at the R&D meet- can cross adjoining cell membranes to development. Yver, now global head, On- ing on what he described as the company’s create a “bystander effect” in the hetero- cology R&D in the newly established Daiichi “flagship asset” in oncology, the antibody- geneous tumor microenvironment and kill Sankyo Cancer Enterprise, told the Tokyo drug conjugate (ADC) DS-8201, which com- neighboring malignant cells. meeting that he joined his new employers prises an anti-HER2 antibody attached by Published online 15 December 2016 “due to the quality of the science.” the company’s proprietary peptide linker Daiichi Sankyo had already laid out its and payload technology to a novel and po- CLICK strategic plans for the sector earlier this year, tent DNA topoisomerase I inhibitor. Read full story at: when it said as part of a new five-year busi- The therapy is currently in Phase I for HER2- http://bit.ly/2hLA1uV ness plan that it was aiming to build oncolo- expressing advanced or metastatic breast or Scrip Awards Winner 2016 Best Contract Research Organization (Niche providers)

This Award for CROs that provide niche services went to Altasciences Clinical Research. Altasciences offers comprehensive Phase I/II drug development including the full array of required support services.

It has improved its range of services to meet sponsors’ expanding needs, leading to the development of Winner: Altasciences Clinical Research specialized offerings, and the judges also noted its strong social media strategy.

“As a CRO focused on early phase drug development, we are honored to be recognized as a leader in the industry. Altasciences offers all of the services of a large CRO, but with a flexible and customized approach at this critical stage of clinical development.” Scrip Awards Pharma intelligence | informa Chris Perkin, Chief Executive Officer.

scrip.pharmamedtechbi.com 23 December 2016 | Scrip intelligence | 19 HEADLINE NEWS

Turkey Adopts New Investment Incentives But Pharma Wary AHMET SEVINDIK

A new government decree on incentives for investment has gone into effect in Turkey, bringing many potential benefits for eligible greenfield projects, but continued currency and political volatil- ity, and more attractive alternatives, mean that multinationals are likely to keep their distance for now.

new “Decree on Project Based Government Incentives for In- vestment” went into effect In Turkey in November in relation Ato greenfield investments valued at more than $100m, but the continued political and currency instability in the country, along with unresolved drug pricing concerns, mean that the pharma sec- tor is unlikely to take advantage of the new measures for now. Local media have pointed out the rich “menu” of incentives that investors can choose from under the decree, including: exemption from customs duty and value added tax (VAT); VAT refunds; tax cuts or exemptions; government support for employer’s social security Mortula Luciano Shutterstock: contributions; government support for qualified employees; capital support; public purchase guarantees; land allocation; support for in- PEER GROUP frastructure; and reduced bureaucratic red tape. Besides pricing considerations, another point preventing multina- These incentives will be available for those companies making in- tional pharma firms from being upbeat over the new investment vestments of over $100m that create “medium or high technology incentives is the fact that there are no known plans by companies in at OECD standards”, have a “significant impact” on foreign trade, de- the peer group to make new greenfield investments in Turkey. crease Turkey’s dependence on imports, and meet a critical need of So far, only three multinationals have disclosed new projects this the country, the government said. year. Merck Sharp & Dohme Ltd. announced a $80-100m investment The Ministry of Economy will be the arbiter of whether investments (but spread over seven years), which includes production of hepatitis meet these conditions or not, and is also authorized to issue invitations A and MMR (measles, mumps and rubella) vaccines and in which Ko- to multinational companies to invest in Turkey under the scheme. cak Farma will be a local partner. Servier SA has decided to move some of its production operations CONTINUED VOLATILITY from France and Ireland to Turkey, and has partnered with two local However, the decree comes at a volatile time in Turkey, where the lira companies, major player Abdi Ibrahim Ilac Sanayi ve Tic AS and Ilko is rapidly losing ground against the US dollar and euro, and - despite Ilac. Sanofi has also said it wants to manufacture an insulin analog the government’s best efforts to encourage foreign investments - product in Turkey, for which negotiations with the government have continued economic volatility and political instability is discouraging already started and a local partner will help implement the project. FDI across all sectors of the economy. However, a common denominator across all these projects is that Since July, when a failed military coup attempt took place, the lira they include partnerships with local firms and only limited technol- has depreciated 17% against the US currency and 12% against the ogy transfer from abroad. Partnering up makes sense for multina- euro. This strong depreciation is particularly bad news for the phar- tionals as local companies have been investing in their production maceutical industry as it exacerbates local drug pricing issues, and is facilities in recent years, which has led to many facilities with good likely to further dissuade any new investment commitments. technology and GMP standards, but unused capacity. The average euro exchange rate applicable to imported drugs in As another business alternative to new capital investment in Tur- 2016 will be calculated by the Price Valuation Commission of the SGK key, multinationals can always acquire good selling local product (the state reimbursement body), based on the Turkish Central Bank’s portfolios and manufacture them in existing facilities. selling rates. 70% of this average value will then be used to set the So against this background, and taken from the perspective of euro rate for 2017 and to determine the prices of imported drugs. multinational pharma companies, it is difficult to see how the new Taking into account the strong depreciation of the Turkish curren- investment incentives might help attract major new greenfield for- cy, particularly in the second half, it is almost certain that the resulting eign capital from the sector, particularly as the wider general vola- rate will not be satisfactory for pharmaceutical companies. In fact, it tility means it is not a good time to build up sizeable fixed assets has become known that the government is preparing a new pricing in Turkey. decree for the industry that - although it is not finalized yet - may Published online 12 December bring further concerns. From the editors of PharmAsia News.

20 | Scrip intelligence | 23 December 2016 © Informa UK Ltd 2016 STOCKWATCH

A Biopharma Nativity Play The cadence of the news in the biopharmaceutical space slowed significantly last week in the run-up to the holidays. In seasonal spirit, Andy “the innkeeper” Smith assigns roles in the Christmas nativity play to those who did come forward – including Ophthotech, Amicus and Lilly. ANDY SMITH

laying the part of King Herod, Oph- “unfortunate” that the results of the Fovista the data that it requested a further Phase thotech Corp. reported the complete Phase III studies were “resoundingly nega- III study. With the company having lost Pfailure of the two long-anticipated tive” while those from Citigroup showed an over half its value over the year to date, Phase III clinical studies for its aptamer Fo- admirable level of introspection in report- Amicus’ investors probably wouldn’t have vista (pegpleranib) in combination with ing that “we were wrong” and concluding found a dilutive stock offering palatable Lucentis (ranibizumab) in the treatment of that Opthotech’s Phase IIb program was after the stock price fall in response to re- age-related macular degeneration (AMD). “surprisingly unreliable.” The Ophthotech cent FDA guidance. In the same way as nativity plays are stock price finished the week down about With Amicus’ and NantHealth’s track re- performed every year, there was a dis- 75%. In comparison, the NASDAQ Biotech cords in the destruction of shareholder turbing regularity to Fovista’s failure. The Index rose by 1.9%. value the roles of manger animals in the practice of using the trade or proprietary nativity play surely beckon. name of a drug rather than the generic BLUEBIRD, AMICUS, Still, if fund-raising after failure is the name for many years before the results NANTHEALTH OFFERINGS order of the day, then Ophthotech share- of the pivotal trial are known is getting to One of the gifts of the Magi – gold, or at least holders should expect a convertible offer- be as predictive of ultimate failure as the its US dollar equivalent – has been making ing sometime soon. Loss-making big data star of Bethlehem was of the birth of a an increasingly prominent appearance in the cancer analytics play NantHealth has the Messiah. The comprehensive failure of Fo- run-up to the holiday season as companies dubious record of completing its IPO at its vista – which appeared to perform worse take the opportunity of office party-induced second attempt at the height of the Janu- than Lucentis alone in many endpoints lethargy amongst investors to raise money. ary 2016 sell-off in biotech. It closed last – was also an echo of the same manage- Bluebird bio Inc.’s recent $250m stock offer- week down 26% from its IPO price. With ment team’s commercial failure at Eyetech ing followed its share price peak after its one Amicus’ and NantHealth’s track records in Pharamaceuticals Inc. where Fovista start- major conference presentation of the year the destruction of shareholder value the ed development. Eyetech’s other aptamer – before it usually goes into clinical trial up- roles of manger animals in the nativity play Macugen (pegaptanib sodium) was also date hibernation – which the analysts from surely beckon. far less efficacious than Lucentis. While Roth Capital described as “leaving room for The part of Gabriel in the nativity play many social media commentators were optimism.” Bluebird’s stock offering has lost could have been assigned to Eli Lilly & Co. quick to express disdain at the significant its participating investors over 6% since its is- last week as it took the opportunity to issue stock sales by Ophthotech’s management sue. To avoid these instant losses from equity above-consensus 2017 sales and earnings on the run-up to the Fovista Phase III stud- issuance where there is absolutely no room guidance that so encouraged investors ies, had they known of the same teams’ left at the inn to make money, two biotech that its stock price rose by over 7%. I have wholesale divestment of Eyetech stock companies raised convertible debt offerings found the recent media preoccupation at its IPO and subsequent secondary of- last week. A $250m offering from Amicus with fake news passé: biopharma compa- ferings, this surrogate marker for a lack of Therapeutics Inc. came bearing a 3% cou- nies have been generating fake news un- confidence in the role of aptamers in AMD pon and a $115m offering from NantHealth der the forward-looking statement waiver would not have come as a surprise. Inc. bore a riskier 5.5% interest rate. for years. Lilly’s new forward-looking guid- While most of the investment bank The outcome of convertible debt issu- ance should probably be bathed in the analysts covering Ophthotech might have ance by loss-making biotech companies same light as its oft-promoted but continu- been angling for a part as one of the three is generally not good, and interest rates ally dashed hopes for the success of solan- kings in the nativity play, their failure to aside, it is difficult to determine which of- ezumab in Alzheimer’s disease. Unlike the predict Fovista’s demise relegated them to fering is the riskiest investment. Loss-mak- Bible, it should not be taken as gospel. a supporting role in the Roman adminis- ing Amicus has spent many years guiding Published online 19 December 2016 tration. Having had “Buy” or “Outperform” to an accelerated approval for its small recommendations on Ophthotech in the molecule chaperone treatment migala- Andy Smith gives an investor’s view on life run-up to Fovista’s failure (and not having stat for Fabry disease. The filing was to be science companies. He has been lead fund read any of my recommendations going supported by clinical data that appeared manager for four life science–specific funds, back to 2011); the analysts from Leerink to be as reliable as those generated by including 3i Bioscience, International Bio- Partners described the failure as “unex- Ophthotech’s Phase IIb study. After a technology and the AXA Framlington Biotech pected” and “not in line with [their] expec- number of false starts with the regulators Fund, and was awarded the techMark Tech- tations.” The analysts from Cowen found it the FDA was recently so unconvinced by nology Fund Manager of the year for 2007.

scrip.pharmamedtechbi.com 23 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 9–15 December 2016

LEAD COMPANY/PARTNER COMPOUND INDICATION COMMENTS Phase III Suspended Fovista (pegpleranib) added to wet age-related macular OPH1002, 1003; primary endpoints Ophthotech Corp. ranibizumab degeneration not met. Phase III Results Phase IV PLATO study; when added metastatic castration-resistant to abiraterone and prednisone, Astellas Pharma Inc./Pfizer Inc. Xtandi (enzalutamide) prostate cancer Xtandi did not meet primary endpoint. Phase III Interim/Top-line Results The adenosine A2A receptor Kyowa Hakko Kirin Co. Ltd. istradefylline (KW-6002) Parkinson’s disease antagonist did not meet its primary endpoint. PATENCY-1; missed primary Inc. vonapanitase chronic kidney disease efficacy endpoint, positive secondary endpoints. complicated urinary tract infec- EPIC, CARE; met primary endpoints Achaogen Inc. plazomicin tions, serious carbapenem-resist- in UTIs, and mortality reduction ant infections (CREs) favored plazomicin in CREs. Synergy Pharmaceuticals Inc./ irritable bowel syndrome with plecanatide IBS-C; met its primary endpoint. Ironwood Pharmaceuticals Inc. constipation Phase III Initiated BioMarin Pharmaceutical Inc./ An analog of C-type natriuretic vosoritide achondroplasia Chugai Pharmaceutical Co. Ltd. peptide, evaluated in children. Shanghai Henlius Biotech trastuzumab biosimilar (HLX02) breast cancer Taking place in China. Phase III Announced MATCH, ALLELE; after ATA-129 (allogeneic EBV-specific posttransplant lymphoproliferative Atara Biotherapeutics Inc. hematopoetic cell or solid organ cytotoxic T-lymphocytes) disorder transplants. Source: Biomedtracker

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22 | Scrip intelligence | 23 December 2016 © Informa UK Ltd 2016 APPOINTMENTS

Shire has appointed Nawal Ouzren ment. Finally, Theorell has been appointed fairs. Previously, Garceau was CMO and head, global genetic disease franchise. Pharmalink’s quality assurance and drug executive vice president of research and She joins the company from Baxalta safety director and has previous experience development at NPS Pharmaceuticals Inc; where she was vice president for the working at large and mid-size companies. and before this he held executive clinical global franchise and before and development roles at Sanofi-Aventis, this, she was vice president of biosimilars Exelixis Inc. has appointed Susan Hubbard Aventis and Pharamacia- (Pfizer). at Baxter’s BioScience business. Ouzren executive vice president of public affairs and also previously served as a lean six sigma investor relations. Stefan Krauss has also David Zaccardelli has been appointed black belt at Baxter’s Lessines, Belgium joined the company as vice president of Cempra Inc.’s acting CEO and David production facility, head of quality at the business development. Hubbard previously Moore has been promoted to the newly Neuchatel, Switzerland plant, and senior served as an independent public affairs and created position of president and chief director of business operations for the investor relations consultant to the biop- commercial officer – effective immediately. BioScience organization. harmaceutical industry and spent over two Zaccardelli served in various senior man- decades at Gilead Sciences in various roles agement roles at United Therapeutics and Pharmalink AB, a specialty pharma com- including vice president of investor relations. before this, he founded and led a startup pany, has appointed Kari Sandvold, Nora Before Exelixis, Krauss was senior director of company focused on contract pharma- Sjödin, Ann-Kristin Myde and Liselotte business development and licensing at Bax- ceutical development services. Prior to this Theorell to key positions on its team. Sand- alta and prior to this, he was director of search role, Moore spent 14 years in commercial vold has been appointed vice president of and evaluation oncology in the global busi- leadership roles at Johnson & Johnson’s pharmaceutical development and manu- ness development unit of EMD Serono. Ortho-McNeil and Janssen Pharmaceutical facturing and most recently she was head division. He was also chief business officer of pharmaceutical development at Orexo Enterome SA has appointed Jai Patel and vice president of worldwide commer- AB. Sjödin joins Pharmalink as vice president chief medical officer (CMO) andRoger cial operations of Tranzyme Inc. of regulatory affairs and brings over 20 years’ J. Garceau non-executive director. With experience to the company. Previously, she more than 25 years of experience and a Robert Waters, Astellas Inc.’s former was global regulatory affairs director at As- background in international clinical devel- global regulatory lead, has joined the Ox- traZeneca; and before Pharmalink, she sup- opment and regulatory affairs, Patel most ford-based retinal company, Oxular Ltd., ported companies as a principal consultant recently was chief medical & scientific offic- as vice president of regulatory affairs. Pre- at NDA Regulatory Service. Myde joins the er NephroGenex Inc. Before this, he spent viously, Waters held various key European company as project director and has 25 20 years at GlaxoSmithKline plc, where he regulatory roles including head of ophthal- years of experience working in global phar- served as vice president in clinical research, mology and head of regulatory develop- ma companies and leading drug develop- medical affairs and global regulatory af- ment at Allergan plc. 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. 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scrip.pharmamedtechbi.com 23 December 2016 | Scrip intelligence | 23 Pharma intelligence

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