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October 16th 2015 No 3773 scripintelligence.com

Lemtrada ‘Acts Like Chemotherapy For MS’ At 5-Years Around two thirds of patients on Genzyme’s multiple sclerosis treatment Lemtrada (alemtuzumab) need no additional treatment up to four years after the two courses of infusion that make up its standard treatment schedule, according to Genzyme’s Mike Panzara, therapeutic area head of MS, neurology and ophthalmology. “It’s important to understand and identify this subgroup that didn’t require additional

treatment,” he told Scrip from the annual lassedesignen/shutterstock.com European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) meeting being held last week in Barcelona. “We’re looking for potential biomarkers now.” Genzyme, a Sanofi company, presented SEEKING ANSWERS: Genzyme to research multiple abstracts of data from clinical trials biomarkers for five year remission subgroup involving its newer MS drugs Lemtrada and Aubagio (teriflunomide). Most notably, in the extension of two across relapse, disability, brain atrophy and number of patients are in a stable state of Phase III pivotal studies (CARE-MS 1 and MRI lesion activity. However, Panzara would remission for up to five years following the CARE-MS 2), 68% and 60% respectively not go as far as calling Lemtrada – a CD52- first infusion. We’ll keep looking at that for of Lemtrada-treated patients needed no targeting monoclonal antibody – “curative” another five, 10 and even 15 years and hope additional infusions in the prior four years. in this subgroup of relapsing remitting MS to be able to say the same.” There were also consistent effects seen (RRMS) patients. “All I can say is that a sizeable Turn to page 4 What Do Express Scripts’ Repatha, Praluent Deals Mean? After all the handwringing about whether the US, said it has sealed deals for both calls for capping future cost increases and payers would cover the newly approved drugs – declaring it has scored discounts on managing who gets the cholesterol-lowering proprotein convertase subtilisin/kexin 9 the medicines, which means neither will be medicines, which is aimed at lowering costs (PCSK9) inhibitors Praluent (alirocumab), excluded from its formulary. for its plan sponsors. marketed by Sanofi SA and Regeneron Express Scripts said its agreements with While Express Scripts said it has locked in Pharmaceuticals Inc., and Repatha the PCSK9 inhibitor makers to put Praluent reduced prices from Sanofi and Regeneron (evolocumab), from Amgen Inc., Express and Repatha on the PBM’s “national preferred on Praluent, whose wholesale acquisition cost Scripts Holding Co., the largest pharmacy formulary” – the nation’s largest formulary was set at $14,600, and Amgen on Repatha, benefit management (PBM) company in covering about 25 million Americans – also Turn to page 8

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Lucie Ellis, Creative Content Reporter, 4 Scrip Intelligence

I recently conducted a group of interviews 1 Lemtrada ‘Acts Like Chemotherapy 14 R&D Bites For MS’ At 5-Years with three management level female 16 Sanofi Builds Indian Sugar Clinics executives from Bayer Group. Inevitably we 1 What Do Express Scripts’ Repatha, 16 Pharma Grapevine: Puppetry, ended up on the topic of women in business: Praluent Deals Mean? Pumping Iron And Patent Shoes specifically women in pharma. The numbers alone tell the story well… 3 Did Biopharma Really Lose 17 Policy & Regulation Briefs In TPP Trade Deal? and it’s an unfavorable tale. 18 Stockwatch: Colors Of The Fall Only 16% of top tier senior executives in 4 Neurocrine Ready To Take On Teva the top 20 pharmaceutical firms, ranked by 20 Expert View: 3D Printing – A Brave 6 Profile: Cipla’s Hamied On Cambridge, New World For Pharma And Patents 2014 sales, are female, against 84% of men in O-Levels And Sticking It Out power positions. 21 NHS Innovative Drug Scorecard Paints On the top 20 boards of directors, the story 7 Unique Funding Pans Out For Visterra Unclear Access Picture is similar: only 23% of directors are women, 8 FDA: Sun’s Elepsia Approval 22 US Capitol Capsule: Advance Science, leaving 77% of all directors men. Was ‘Erroneous’ Don’t Pressure FDA On Approvals, While the situation is obvious, the reason Drug Chief Tells Advocates for this massive gender gap is not as clear. 9 Don’t Pick On Poor Valeant 23 Pipeline Watch Many pharmas are outspoken about their 9 Will Firing Leif Save Arena? intensions to build up numbers of female 24 Appointments executives. And in biotech the amount of 10 Business Bulletin female CEOs has risen sharply in recent years. 11 Spark Restores Vision In PhIII; But the very top level in pharma remains Hopes To Lead Gene Therapy unmovable. Even at Bayer, where I easily found three senior women to chat to, the 12 Who Will Get First AD Drug highest power positions are all filled by men. To Market In Over A Decade? In my opinion, big pharma is stuck in a 13 Meet The Company Giving Patients bit of time warp. The same people have Access To Unlicensed Medicines circulated the same group of companies for too long. Fresh blood is needed to revive aging business models. I’m not saying the solution to all problems is to chuck a load Scrip of women in there and let them fix it. What I am saying is the timing is almost perfect Editor: [email protected] Managing Editor: [email protected] for new executives with bold ideas to move News Editor: [email protected] up the ladder. Big pharma needs a shake-up South Asia Editor: [email protected] and if the result of this is more than 16% Washington Editor: [email protected] US West Coast Editor: [email protected] of powerful women get noticed for their Features Editor: [email protected] leadership qualities and business prowess, Senior Reporter: [email protected] then I’d call it a win. Principal Analysts: [email protected]; In the words of one of my interviewees, [email protected]; [email protected] We would love to hear your comments about Reporter: [email protected] Scrip’s coverage. Feel free to tweet us or post Jessica Federer, head of digital at Bayer [email protected] Reporter: a discussion on our LinkedIn group, for your Healthcare, “It’s 2015! We know the Creative Content Reporter: [email protected] chance to interact with editor Editorial Assistant: [email protected] Eleanor Malone importance of gender equality and diversity. Production: [email protected] and the rest of the Scrip Intelligence team. No more excuses.” Pharma Data Editor: [email protected] Read more on this story on Scrip’s website: Global Content Director: [email protected] Follow us at: @scripnews http://ow.ly/TcC3m All stock images in this publication courtesy of www.shutterstock.com unless otherwise stated. Join us at: linkd.in/scripintelligence And look out for the full interviews from Customer Services three Bayer women working in pharma in Tel: +44 (0)20 7017 5540 or (US) Toll Free: 1 800 997 3892 next week’s edition of SCRIP Intelligence. Email: [email protected] To subscribe, visit scripintelligence.com To advertise, contact [email protected] Scrip is published by Informa UK Limited. ©Informa UK Ltd 2015: All rights reserved. ISSN 0143 7690.

2 October 16th 2015 @scripnews scripintelligence.com © Informa UK Ltd 2015 headline news Did Biopharma Really Lose In TPP Trade Deal? After more than six years of intense efforts Froman said that in debating the exclusivity abusive intellectual property protections for to lobby a group of Asia-Pacific trade issue, the ministers all recognized the pharmaceutical companies.” ministers – a pact that eventually involved “importance” of innovation and having Peter Maybarduk, director of the Access representatives from 12 nations – the effective market protection for encouraging it. to Medicines Program at the Washington innovator biopharmaceutical industry failed to But he said there also was a “recognition that consumer watchdog Public Citizen, warned get what it most wanted in the Trans-Pacific there may be multiple ways of achieving that.” that those government “mechanisms” Froman Partnership (TPP): 12 years of data exclusivity “The outcome, I believe, both encourages mentioned, but gave no clear details on, protection for biologics against biosimilars. and incentivizes the innovation around could be used by the USTR to “browbeat But did brand-name biopharma really lose important life-saving medicines and treatments countries, now and in the future, to get what in the TPP? and ensures access to affordable medicines big pharma wants, and pull countries toward While it didn’t get 12 years across the more broadly around the world,” he said. longer monopoly periods.” board in all 12 TPP nations – Australia, Brunei Maybarduk said the final Asia-Pacific trade Darussalam, Canada, Chile, Japan, Malaysia, Unhappy Innovators deal does not appear to adhere to the standard Mexico, New Zealand, Peru, Singapore, US and But Jim Greenwood, president and CEO of the under the so-called May 10th 2007 Agreement Vietnam – the innovator biopharma industry Biotechnology Industry Organization (BIO), – a deal reached by Democratic congressional did get a “minimum” of five years, and that’s begged to differ, declaring that his group leaders and the Bush administration – on significant, considering more than a third was “very disappointed” in the outcome access to affordable medicines, which he said of those countries currently don’t have any of the TPP negotiations over exclusivity could complicate the TPP’s prospects at getting exclusivity protection. protection, calling it “short-sighted,” with the through the US Congress. Plus, US Trade Representative (USTR) potential to “chill global investment” and “slow Michael Froman noted during an Oct. 5 press development” of new treatments. 21st Century Trade Deal conference that individual nations will be “BIO strongly believes that 12 years of data But in declaring they had sealed the TPP deal able to use “government measures that can exclusivity is a prerequisite to attract the on Oct. 5 – although some finalizing of the text achieve a comparable outcome.” investment required to continue medical still needs to take place – the 12 trade ministers “For some of us, in our systems we use innovation and develop new biological cures said they achieved their goal of reaching an data protection as the method for creating and therapies,” Greenwood charged, insisting ambitious, comprehensive, high standard effective market protection,” Froman that what Congress established under the and balanced agreement, which they insisted explained, noting the US supports 12 years BPCIA was the “appropriate period” to foster would “benefit our nation’s citizens.” under the Biologics Price Competition and innovation and provide access to biosimilars “TPP brings higher standards to nearly 40% Innovation Act (BPCIA) – the law that granted in a “reasonable timeframe.” of the global economy,” Froman said. “We think the FDA the authority to approve biosimilars “This term was not a random number, but it helps define the rules of the road for the Asia- – while other nations have eight or 10 years, the result of a long debate in Congress, which Pacific region in a way that’s consistent with although Brunei, Malaysia, Mexico, Peru determined that this period of time captured the interests and the values that we share.” and Vietnam currently have no exclusivity the appropriate balance that stimulated Froman noted that the 12 ministers and protection. research but gave access to biosimilars in their staffs were working on the TPP until a timely manner,” John Castellani, president 5am EDT on Oct. 5 – pointing out the press First Trade Deal With Exclusivity and CEO of the Pharmaceutical Research and conference that had been set for the day Froman pointed out that the TPP is the Manufacturers of America, said of the 12 years before had been rescheduled several times. “first trade agreement in history to ensure a under the BPCIA. “At the end of the day, here we are as 12 minimum period of protection for biologics,” But Chester “Chip” Davis, president and CEO TPP partners having achieved something and by putting such measures in place, he of the Generic Pharmaceutical Association – that some time ago people didn’t think was insisted it would “help set a reasonable model who used to be a lobbyist for PhRMA before achievable,” said Canadian trade minister and will create an environment in which recently switching teams – praised the TPP Tim Groser, who praised his colleagues for through comparable treatment there will be agreement as an effort to improve worldwide getting a “21st century high-ambition trade an effective period of protection to encourage patient access to affordable medicine. agreement actually negotiated, getting it both innovation and access.” done, one that is going to serve us very well He said the debate over biologics Angry Patient Advocates and will set the rules for the 21st century for exclusivity was “one of the most challenging Médecins Sans Frontières/Doctors Without trade within the Asia-Pacific region.” issues in the negotiations.” Borders, however, said it was dismayed by In the US, President Barack Obama But, Froman said, “We’ve worked the TPP deal, asserting the agreement would cannot sign off on the TPP for at least 90 cooperatively with all of our TPP partners to “raise the price of medicines for millions by days, although his administration is already secure a strong and balanced outcome that unnecessarily extending monopolies and further claiming it as one of his major achievements. both incentivizes the development of these delaying price-lowering generic competition.” Under the trade promotion authority – new life-saving drugs, while ensuring access “The big losers in the TPP are patients and commonly called fast-track – which Congress to these pioneering medicines and their treatment providers in developing countries,” granted in June, the full text of the TPP must availability.” the humanitarian group said, declaring the be made available to the American public for “What we are doing in TPP is recognizing deal would “go down in history as the worst 60 days before lawmakers vote on it. Congress that we’re all trying to achieve that effective trade agreement for access to medicines also can only give the TPP an up-or-down market protection and deliver a comparable in developing countries, which will be vote and cannot amend or filibuster it. outcome through various mechanisms,” he said. forced to change their laws to incorporate [email protected]

© Informa UK Ltd 2015 @scripnews scripintelligence.com October 16th 2015 3 headline news Neurocrine Ready To Take On Teva Lemtrada ‘Acts Like Chemotherapy For MS’ At 5-Years (Continued from page 1) Lemtrada’s safety profile has relegated the product to at least third-line in the treatment of multiple sclerosis, but the five year data presented at ECTRIMS could change the Lemtrada story, Datamonitor Healthcare lead analyst Daniel Chancellor told Scrip. “It’s exciting because there are some patients who only need two short courses of treatment at month zero and month 12 and then nothing else. Lemtrada is essentially behaving like a chemotherapy, like its original use in leukemia. And of icsnaps/shutterstock.com course there will be cost implications of only having to pay for these two courses, whereas all the other treatments for MS are required for the rest of a patient’s life.” Neurocrine sizes up its first shot to Lemtrada’s price tag of around $160,000 is play against Teva in the big leagues relatively palatable if only two courses are needed, notes Chancellor. Neurocrine Biosciences Inc. is readying its The biotech intends to use this data, as well Other data presented at ECTRIMS Phase III movement drug for a filing with the as data from KINECT-2 and earlier studies to highlighted that both Lemtrada and Aubagio FDA next year and is prepared to take on its file a New Drug Application with FDA in 2016. “slowed brain atrophy” in MS patients, much-larger competitor, Teva Pharmaceuticals noted Panzara. “Other MS treatments have – investors clearly believe they can do it, How It Stacks Up demonstrated this,” he admitted, “but not in pushing the stock up on the news. Neurocrine’s NBI-98854 would compete with a manner that has been consistent across Neurocrine jumped more than 10% to Teva’s Austedo (SD-809), which the Israeli studies, apart from Gilenya (fingolimod). When trade near $43 on Oct. 8 after the biotech company picked up in its $3.2bn acquisition you put this together with the data we have announced positive results from its Phase of Auspex Pharmaceuticals. Both drugs inhibit in reduction in disability progression, it makes III trial of NBI-98854 in patients with dopamine through the VMAT2 pathway. a difference.” tardive dyskinesia who have underlying “Our research with our psychiatrists and Aubagio sales growth has been slow schizophrenia. neurologists, and the market research that our but steady, Panzara added. “We launched The VMAT2 inhibitor is meant to help with commercial group is embarking on, all tell us it without as much fanfare as others might the involuntary muscle movements – like lip people like the idea of a once-a-day drug that have launched their new MS drugs. It smacking, tongue protrusion, lip puckering doesn’t require titration, that doesn’t have such was approved on the basis of one study; and facial spasm – caused by the prolonged a narrow therapeutic window that you have to physicians started using it, they had good use of older antipsychotic patients who have titrate,” said O’Brien. “Again, we will see when experiences – anecdotally the word we hear taken the drug to control conditions like -- we look forward to taking our data into the a lot to describe the drug is ‘quiet’ – and schizophrenia, schizoaffective disorder, bipolar commercial marketplace. I think physicians like we’ve added to the body of data. So yes, it’s disorder and major depressive disorder. what they see when they see this data.” doing well.” The late-stage KINECT-3 trial showed Analysts also believe that NBI-98854 would The incidences of PML that continue to that at six weeks, patients taking the 80mg hold up well competitively against SD-809. blight other MS products is not something dose of the drug showed a 3.1 reduction Leerink Swann analyst Paul Matteis admitted in that Genzyme concerns itself with. “When compared with placebo on the Abnormal an Oct. 8 note to investors that a comparison we talk to physicians, we focus on our own Involuntary Movement Scale (AIMS). of the drug’s data is not apples to apples. data and our own side effect profiles. Every Patients taking the 40mg dose were also “However, ‘809 was able to generate a 1.4 product has its own benefits and risks, and assessed and Clinical Global Impression of point placebo-adjusted benefit on the AIMS that is what we focus on.” Change (CGI-TD) for both doses was studied score versus 3.1 and 1.8 points for the 80mg as a secondary endpoint. and 40mg NBI-98854 doses. Mechanistically, it Gilenya at ECTRIMS The biotech’s Chief Medical Officer Chris is unclear to us why the two products would Novartis presented its own long-term O’Brien said during a call with analysts have differentiated safety profiles as they both efficacy data of Gilenya at ECTRIMS, citing on Oct. 8 that the company began seeing inhibit dopamine release through VMAT2, and ‘no evidence of disease activity’ based on signs of improvement in patients on the thus the varying effects may be due to patient four parameters: relapses, MRI lesions, brain drug at two weeks and that doses got better populations, chance, timing of evaluation, shrinkage and disability progression (NEDA- over time. or study design. However, in any case, this 4)). According to Novartis, 31% to 45% of Neurocrine intends to publish the full could improve perception of ‘98854 in the patients continuously treated with Gilenya results of the study in a major medical journal marketplace, important for NBIX given the in the FREEDOMS core and extension trials and will continue an open-label extension of difficulties competing with TEVA’s commercial achieved NEDA-4 in each of the years three to KINECT-3. NBI-98854 is also being studied in CNS franchise,” he wrote. seven after treatment initiation. patients with Tourette syndrome. [email protected] [email protected]

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Art: PXL15004A_002A2_SWOP3.tif (CMYK; 284 ppi; Up to Date), PXL- PAREXEL wTag Gray-4C.ai (Up to Date) profile Cipla’s Hamied On Cambridge, O-Levels And Sticking It Out Cipla’s journey over the years is steeped in levels at the age of 18, military service was history. Chair Yusuf Hamied recalls growing compulsory. So all the students in class with up in the midst of leaders of India’s freedom me had done two years of military service and struggle, including Sarojini Naidu who became were 20. When the lectures started, the teachers president of the Indian National Congress, had to review things because those students Zakir Husain (who became the President of had not really studied for two years. And that’s India), BG Kher (chief minister of Bombay) and what saved me. Otherwise, I’d have been very Sardar Patel (India’s first home minister and backward! I had to work for the first two years deputy prime minister), among others. for virtually 10-15 hours a day to catch up. Hamied’s father and Cipla’s founder, K A I finished my PhD at the age of 24. When I Hamied, supported Mahatma Gandhi’s Non- finished my PhD, I was offered a fellowship at Co-operation Movement against British rule. Christ’s College but I turned it down. Because, When Gandhi visited Cipla in 1939 he was in my heart of hearts, I knew that there were said to have urged the company to supply many chemists in the laboratory who were medicines for the Indo-British war effort. much cleverer than me. Yusuf Hamied’s mother was Jewish and his Dr Yusuf Hamied grandparents were killed in the Holocaust. AG: You have been living largely in the In a candid interaction with Scrip’s Anju UK and have watched and steered your Ghangurde in Mumbai as part of our ongoing I think what really shaped us was the variety company’s growth in India… two quite executive profile series, Hamied recounts the of people that we met as kids. In those days different worlds. What was the journey like influence of the late Lord (Alexander) Todd, there was no TV, hardly any radio… so people and the key challenges? Nobel Laureate and master of Christ’s College, used to meet more often. One thing that my YH: I came back in 1960 but I still kept Cambridge, on his life; how he nearly packed parents allowed the children to do was mix in touch with Cambridge and science up and left India between the 60s and the with their friends. So we grew up meeting all in particular and we’ve seen Cipla grow. early 70s; and his views on religion. my father’s friends. In my growing up years, When I first came here Cipla’s turnover was I met Zakir Husain, Sarojini Naidu, Sardar INR4,800,000 [now $73,271] the entire factory Anju Ghangurde: You arrived as an infant Patel, Morarji Desai, BG Kher. My father was a was this building where we are now seated. at the Gateway of India in Mumbai, member of the legislative council. It is really We went through a rough period from which your father, in his autobiography, something…the way we grew up. the 60s to the early 70s. How often during refers to as an auspicious place and one that period I very nearly packed up and left reserved for the landing of kings and AG: What about the years at Cambridge? India. The pharma industry was dominated princes. Has that probably played out, in YH: First it was Cathedral School in Bombay by multinationals and we formed the Indian some ways, in your life? (now Mumbai). I was generally among the top Drug Manufacturers’ Association. Even at that Yusuf Hamied: No, I would put it students, particularly in science subjects. time we were always fighting monopoly. But I slightly differently. In 1952, my father was made Sheriff of still feel the entire Indian bureaucracy was, at The origin of all that was…my mother was Bombay. The sheriff was required to receive that time, sold out to foreign firms. Lithuanian, my father Indian. My father went foreign dignitaries. In 1953, I got my results Yet some of us stuck it out. What you see to study in Germany in 1925; my mother was of senior Cambridge O Level and the results today is certainly an outcome of the past. I also studying there. were fairly good. One of the dignitaries who don’t think people really even today appreciate But the story goes back. In 1920, Gandhi came to India during that time was Lord that….the struggles we had in those days with had given a call for students to boycott Todd [then the master of Christ’s College, some foreign firms. Those are legendary stories. universities in India run by the British Cambridge] and my father as Sheriff had When India’s patent laws changed [India’s [government]. Then my father left Allahabad to go and meet him. One thing that my Patents Act 1970 abolished product patents University, Zakir Husain left Aligarh University. father did was to keep his children with for pharmaceuticals, food and chemicals and They met in Sabarmati Ashram and became him whenever he met people. I was 17 allowed only process patents in these fields], bosom pals. and father told me to carry my results. My we were one of the few companies already in On Gandhi’s request, Zakir and my father father happened to ask Lord Todd what the active pharmaceutical ingredients (APIs). We were sent to Delhi and joined the Jamia Millia minimum qualification was for a student to got our first US FDA approval in 1984. And I Islamia [National Muslim University]. In 1924, study at Cambridge and he said: “We have shared that knowledge with industry. It was a my father insisted that Zakir go abroad to no such rules; we admit anyone we consider different era of co-operation. study and he went to Germany and in 1925, suitable to be a student of our well-known In the 60s and 70s, made in India was my father followed. There he met my mother. university.” I never did A levels and got generally a bad name, at least in pharma. They got married in 1928 in a mosque in admitted to Christ’s College, Cambridge, Nobody would meet us, show us their Berlin and there was also a civil marriage in only on my O level results. Today, I would, factories, buy from India. During that period, London, before they came to India. perhaps, never have got admission. At slowly I tried to put India on the map. I used My sister was born in 1934. Cipla started in that time it was a different era. I joined to promote India. I always believed, then 1935…it was a struggle. I was born in 1936. Cambridge at the age of 18 in October 1954. and today, that if India improves, Cipla will When I was due, my mother said she’d like to Others in my class had done A levels and improve. If I’m fighting patents or saying have her baby at home and the family went in were two years ahead of me. What saved me compulsory licence, I’m not fighting for Cipla. 1936 to Vilnius, Lithuania. was that in those days after you finished A I don’t have any ulterior personal motive.

6 October 16th 2015 @scripnews scripintelligence.com © Informa UK Ltd 2015 profile/headline news

In the late 80s, we were doing APIs, exports Because in 1925, the word “India” did not started booming. Around the time of us exist, we were Hindustan, and every citizen Unique Funding getting US FDA approval, we then thought of Hindustan was a Hindu. Now, let us again that we should look at the global picture and change our name to Hindustan and we are all Pans Out For Visterra not just India. By that time you had the jet Hindus. What difference does it make? On the heels of getting a second grant flights going and you could get to England in from the Biomedical Advanced Research eight-nine hours. AG: Who do you admire in the industry? and Development Authority (BARDA) Today the world has shrunk and you can’t YH: I don’t like the word admire… but of the US Department of Health and restrict yourself to only being an Indian player. prefer the word achievers. I would say what Human Services (HHS), Visterra Inc. is You have to think globally. We started thinking Sun Pharma has done under the Indian ready to advance its broad spectrum globally in the mid-80s. We thought someone circumstances and become global has flu treatment – a drug that could have in the family should globalize and my wife been unparalleled. In the second range, in particular uses in hospitals and during and I decided we could divide our time no particular order, the achievers would potential pandemics. between India and the UK. We got the right of be Dr Reddy’s, Wockhardt, Lupin, Cadila The Massachusetts biotech announced abode in the UK, which took lot of effort. and Glenmark. Special achievers have Oct. 5 that BARDA is contributing another been the Hyderabad [based] companies $29.1m to the development of its flu AG: Who was your biggest influence, like Aurobindo, Hetero and others that are treatments, with the potential to bring in and why? coming up...Divis, Shasun. Hats off to the as much as $204.5m should VIS410 should YH: The three people who influenced me Indian enterprise. BARDA decide to move forward with the the most were my father, Lord Todd and the option. The full funding would span five senior tutor of Christ’s College, Dr Pratt, who AG: How do you get step back and get years and would allow Visterra to pay for admitted me on the recommendation of Todd. perspective? the submission of its Biologics Licensing YH: As long I feel I can contribute Application (BLA) with the FDA. AG: What’s the one corporate action you scientifically or business-wise, I will stay here. VIS410 is a monoclonal antibody meant regret you made or didn’t make? If I can’t contribute, I’ll step down. But again to treat all strain of influenza A, including YH: When I came back to India, the there has to be a team effort. In this team the seasonal strands of the flu and the population in Bombay was around two effort the people in your team must think as highly-mutated forms that have emerged million and yet I saw the writing on the wall… if the company belongs to them. There has to over the last few years. that India’s biggest problem was going to be be a sense of belonging. This could be a major seller for family planning. And that something had to the biotech due to increases in the be done about it. AG: We are seeing non-traditional players incidence of the flu in recent years. In the following years, among other things, like Apple, Google, and Samsung making Companies have struggled to get Cipla took up the manufacture of hormones. inroads into the healthcare space. What patients to take their preventative We set up a factory in Bangalore to produce kind of industry do you envisage say a vaccines, but also have not always essentially hormones for family planning. In decade down the line? been successful with those vaccines 1973, I personally went to the government and YH: The traditional industry will continue. for those patients that are compliant. said that we can offer you the pill at cost price Let us look at the world either from a literacy Flu vaccines typically prevent three to of INR2 per month. At that time the price of the or poverty point of view. I can’t see, in the four of the most common strains of pill in America was around $6 a month. I told Third World or the developing world, major the seasonal flu, but can be completely the government that we didn’t have the muscle changes, at least not in the next decade. I can ineffective against preventing the to market and distribute the product and that I see major changes for people who can afford infection when other strains become was willing to put the Bangalore factory totally in the developed world. You will get all your more prevalent during a season or at the disposal of the government. But they health data on your phone. There will be a highly mutated strains emerge like the turned us down. In retrospect, that was perhaps greater load on diagnostics. H1N1 virus that devastated the US a few the biggest failure in my career… that we were years ago. AG: One myth about industry that you’d not adequate enough to fight the problem of Visterra intends to position VIS410 as like to set straight? family planning. And today, I still believe it is a treatment for patients in the hospital – India’s biggest problem. YH: The Indian industry is being crucified where influenza spreads more easily and internationally. This myth that Indian products where patients with a more severe case AG: What is the best advice you’ve ever had? are substandard, where does it come from? usually end up. YH: I think the best advice was indirectly For example, today, we are making certain Visterra is a unique story; the given to me by my father. He was a Muslim, anticancers…you mean to say the foreign company is funded by a variety of my mother was Jewish…I went to an Anglo- firms have not picked up our products in sources, including the government Scottish Christian school. All my friends in the market and analysed them? And if our grants from BARDA, as well as traditional class and my closest friends are all Hindus. products were not equivalent to theirs, would venture funds and corporate venture We grew up in a total secular environment they keep quiet? investors. It completed a Series B … the 50s, the 60s in India. Even today, And, the gesture shown by one or two financing in October 2014 that included when I’m asked my religion, I write “Indian.” companies to license their products to contributions from Merck Research My contention is that we are all the same India and the Third World, like Gilead, ViiV Labs Venture Fund, Temasek and Vertex stock. When I was young, my father told me Healthcare have done, should be more Venture Holdings. that when my mother first met him in 1925, widespread for the good of the world. [email protected] she said: “You are a Hindu.” And he said: “Yes.” [email protected]

FDA: Sun’s What Do Express Scripts’ Repatha, Praluent Deals Mean? (Continued from page 1) whose WAC is slightly lower at $14,100, Sanders (I-VT) and Rep. Elijah Cummings Elepsia Approval the PBM would not disclose what those (D-MD), who introduced legislation last markdowns came to under the agreements. month aimed at reining in prescription drug Was ‘Erroneous’ In August, Steve Miller, senior vice- costs and stopping price gouging. Cummings The US FDA has stated that its earlier president and chief medical officer at Express and 17 other Democrats have called for approval of Elepsia XR (levetiracetam Scripts, said the PBM would “leverage” Valeant to be subpoenaed to appear before extended-release tablets), the new the competition between the two PCSK9 the House Oversight and Government Reform drug application (NDA) of Sun Pharma inhibitors “to achieve the greatest possible Committee – a hearing that has yet to be Advanced Research Company Ltd (SPARC), discounts for our clients and patients.” scheduled. But with the PCSK9s, Whitrap said was “erroneous.” He and leaders from rival PBM CVS his company will be able to “provide some SPARC, which is the listed spin-off R&D Health Corp. had both argued the PCSK9s assurance to our clients that we are able arm of Sun Pharmaceutical Industries Ltd, had the potential to become the costliest to not only deliver immediate affordability recently received a Complete Response therapies in the US – breaking the American but also long-term affordability. That’s what letter (CRL) for Elepsia XR from the FDA health system’s bank. Miller said it was interests our clients.” rescinding its earlier approval, citing Express Script’s “preference” for the PCSK9 “We are able to keep things at a sustainable the compliance status of the firm’s manufacturers to provide “favorable pricing rate for our clients,” he added. manufacturing facility for the product on so that it would make sense for our national the approval date. formulary to cover both products,” rather than The FDA has now clarified to Scrip that excluding one or both drugs. Putting caps on future costs also the approval occurred when the Center provides predictability for plan for Drug Evaluation and Research was Caps On Future Cost Increases “transitioning” to a new application review In addition to the undisclosed discounts on sponsors so they don’t fall victim system and implementing new processes Praluent, which was approved in the US on July to sudden price escalations for personnel. 24, and Repatha, which gained the FDA’s nod “At that time, the compliance status of on Aug. 27, Express Scripts said it also intends to this facility was not accurately displayed or cap the entire plan cost in 2016 for the PCSK9 Express Scripts estimated that its national appropriately accessed in the new system, inhibitors for clients enrolled in its recently preferred formulary clients collectively will resulting in the erroneous approval of this created Cholesterol Care Value program. spend about $750m on the PCSK9 inhibitors in application,” the FDA told Scrip Oct. 2. Express Scripts spokesperson David 2016, which it said was “far lower than industry SPARC previously said that it hoped Whitrap told Scrip the company has created forecasts.” Whitrap said that figure is actually to market Elepsia XR at a significant “individualized” ceilings for amounts the plan a “small percentage of the national spend premium to generics and was eying sponsors in the national preferred formulary, on this,” although he pointed out Express commercialization in the US by the which is mostly employers, will need to spend Scripts’ clients represent about a quarter of the second half of 2015–2016. on the PCSK9s, “which is much lower than American population for the drugs. The FDA’s clarification is significant they were expecting.” given that news of the CRL and its “It’s a novel approach we are bringing to Controlling Use linkage to Sun’s Halol site, which is to the pharmacy space,” Whitrap declared, noting Express Scripts said its Cholesterol Care manufacture Elepsia XR, had spooked the caps will be “customized” around the Value program relies on “rigorous clinical investors who viewed the CRL as a sign of demographics of the plan sponsors. documentation” to ensure the PCSK9 limited progress at resolving current good Putting the caps on future costs of the inhibitors go to the “right patients, while manufacturing practice (cGMP) issues at medicines also provides predictability for the minimizing unnecessary risks and wasteful Halol, though some analysts maintained plan sponsors so they don’t fall victim to the spending.” that such fears were overblown. sudden price escalations that have been the Whitrap said the firm would require doctors Sun’s Halol facility, seen as a key site for talk of Wall Street and Washington alike in the to show their patients have tried and failed India’s top drug firm, is currently under past month, Whitrap said. statins, rather than just claiming someone is FDA scrutiny for cGMP deficiencies, The move could put more pressure on the statin-intolerant, before Express Scripts would although the company has been working entire biopharmaceutical industry, which cover the use of the PCSK9 inhibitors. with the agency to set things right and already is under attack after companies like In managing who gets the PCSK9s has taken several corrective measures. Turing Pharmaceuticals AG increased the inhibitors, he said Express Scripts is using price of its toxoplasmosis medicine Daraprim The FDA also indicated that the Elepsia the FDA’s labeling and the protocols the (pyrimethamine) by more than 5,000%, which manufacturers have laid out. Express Scripts XR case had little in common with the the CEO has now backed away from, although argued that for the large majority of the more agency’s previous decision wherein it’s unclear by how much, and Valeant than 70 million people with high cholesterol, it rescinded tentative approvals for Pharmaceuticals International Inc., in a similar “statins are the clinically appropriate, tried- Ranbaxy’s generic Nexium (esomeprazole move, raised the costs of Nitropress (sodium and-true therapy.” magnesium) and Valcyte (valganciclovir nitroprusside) from $257.80 to $805.61, “When older therapies are going to be just hydrochloride). or 212.5%, and Isuprel (isoprenaline) from as effective, it’s generally in the best interests of In March this year, Sun announced the $215.46 to $1,346.62, or about 525%. the country and the interests of those patients closure of the merger with Ranbaxy. Both firms have caught the attention of to be on those medications,” Whitrap said. [email protected] congressional leaders, including Sen. Bernie [email protected]

8 October 16th 2015 @scripnews scripintelligence.com © Informa UK Ltd 2015 headline news

Don’t Pick On Poor Valeant Will Firing Leif lost about $100 per share in value in the last month, but that can easily be attributed to a Save Arena? variety of macro-economic factors including Arena Pharmaceuticals finally admitted a slide in the general stock market, as well as things aren’t working for the company

Mr.Nikon/shutterstock.com a pullback from healthcare stocks – and of and has moved to push out longtime CEO course, that whole drug pricing issue. Jack Leif. Trying to put a bright smile on Valeant, in particular, has come under fire the bad situation, the obesity drugmaker since those in the political spotlight have said Oct. 5 that Leif will “retire” at “the chosen to take aim at drug pricing after the request of the board of directors.” New York Times published a story detailing the While immediately beginning a search liberties with pricing Martin Shkreli’s Turing for a new CEO, Arena director Harry Pharmaceuticals has taken. Yet, most analysts Hixson will fill in as interim CEO and Valeant Pharmaceuticals International Inc. are currently rating Valeant’s stock a “buy” principal financial officer. Hixson, 77, does not like to be picked on – by anyone. The and consider this a great time to invest in the has been on the board since 2004. He multi-national conglomerate is whining that company (any analyst would point out that previously served as CEO of Sequenom the mean bloggers are saying nasty things and the fundamentals backing Valeant’s business from 2009 to 2014, where he was tasked Valeant wants to set the record straight. model have not changed and therefore, with turning around the company after The specialty pharma filed a document with the drug pricing issue hasn’t affected the the biotech had a major scandal regarding the US Securities and Exchange Commission investment thesis). the mishandling of data. on Oct. 6 to “correct misleading reports.” In conjunction with firing the The chart-like document lists the source that Doth Protest Too Much management, Arena also intends to said mean things and when, the nasty lies and Valeant’s outcries in the document filed conduct an evaluation of its programs Valeant’s “facts.” The particularly odd part about with the SEC defend the company against and will announce later this year its plans the document is the three sources that Valeant a number of issues, but in particular are for 2016. feels the need to defend itself against – a short- related to price increases. For example, The move is not a surprise to selling research firm, a small Canadian research Veritas Investment Research claimed in an shareholders of Arena, who pushed up firm and a blog by a nameless writer who Oct. 1 report that absent certain price hikes, the stock almost 9% in late-day trading claims to have worked in the industry. While Valeant would never be able to meet its after the announcement. The upward virtually anything can sway investors, these earnings expectations. Valeant contends momentum continued in after-hours sources probably can’t be held accountable for that the acquired products and any price trading of the stock, as it climbed another the dramatic slide the company has seen to its increases were included in said guidance – 5%. The stock currently trades around stock price in the last month. not exactly a denial that the price increases $2.15 per share, but traded as high as Both research firms have released reports are being made. $6.28 in the last 52 weeks and shares recently that are calling out Valeant on the Meanwhile, Citron Research published a reached $13.50 in mid-2012. price increases it has made to several drugs – report on Sept. 27 that included a chart of Arena has been disappointing investors an issue that the specialty pharma has come price increases for Valeant products – and has for several years now as its obesity drug under fire for in recent weeks, while the blog since made a website devoted to the topic. Belviq (lorcaserin) struggled to get has made it a mission to reveal all the evils Valeant argues that the data is presented in approval from FDA and has failed to gain that are Valeant. a way that is misleading because it shows any traction in the market, with annual Valeant’s business model has been a topic increases to wholesale acquisition price (WAC) sales of only $45m. of conversation for years, but came under and does not take into account discounts and Arena isn’t the only obesity drug particular scrutiny when it was making rebates, etc. “For example: since January 2015 developer to struggle. Vivus has also its bid for Allegan earlier in 2015. The Valeant has raised the gross price of Jublia been floundering as well, and took the Canadian company has made no qualms 20% but realized 2% net price increase,” says step to replace its own CEO in 2013. All of about telling the industry that it doesn’t Valeant. The company also argues that most the obesity drug developers face similar believe in spending money on R&D. Instead, of the drugs included in the chart have a challenges – a need for physician education, Valeant has amassed an empire by acquiring generic alternative available. less than stellar efficacy, underwhelming companies and in-licensing drugs that are Much of the document is spent laying out commercial efforts, reimbursement snafus and poor pricing strategies. already on, or near, to market. While many inaccuracies that Valeant found within the Arena doesn’t have much to fall back people in the industry don’t see this as a blog posts by AZ Value Investing, a series of on either; the drug developer is currently sustainable business model – and it likely posts by an anonymous source that doesn’t working on a life cycle management wouldn’t be if every company subscribed to seem to be associated with any business or program for lorcaserin that includes an this bit of wisdom – it has worked rather well research firm. None of the discrepancies have indication in smoking cessation, but has for Valeant. to do with product price increases. little else in its pipeline. What investors What was once a small Canadian While Valeant’s outspoken CEO Michael of Arena should really be wondering dermatology company is now a multi-national Pearson has never seemed the type to suffer is whether a change in management specialty pharma with a market capitalization fools, the SEC filing seems only to be calling can really prompt a turnaround for the over $50bn. Valeant’s stock currently trades more attention to three little-read naysayers. floundering company. at about $165 – well above the $50 per share Begging the question, why did Valeant bother? [email protected] it traded at in 2012. Granted, the stock has [email protected]

Merck Invests In zhangyang/shutterstock.com access and policy research at PDCI Market Access (PDCI), a Canadian pricing and reimbursement Bionomics consultancy. Private insurers are starting to Merck & Co. has expanded its three-year old worry about cost containment and according deal with Australia’s Bionomics, pushing further to PDCI, product listing agreements could into their collaboration in chronic pain. The pair become a prerequisite for companies selling announced Oct. 8 that the extension of the expensive specialty drugs. In an interview collaboration includes the New Jersey-based with Scrip, Mani explained what companies big pharma taking a 5% stake in Bionomics human papillomavirus (HPV), but Advaxis expects need to know about these agreements to get by buying 21m shares at 59 cents apiece. In to get the program back on track “expeditiously” ahead. Canada was the world’s 10th biggest mid-2013, Merck agreed to pay up to $172m without significant interruption to the trials. Even pharmaceutical market in 2014. The private sector generated nearly 60% of drug spending, or in option and milestone fees for Bionomics to so, investors were unhappy that the company did not expeditiously report the news to shareholders, $CDN16.7bn. Private insurers took $CDN10.3bn, use its proprietary ionX genomics-based, ion with the rest generated by out-of-pocket channel-targeting CNS drug discovery platform pushing Advaxis from $10.31 when the stock market closed to $7.65 after hours. The FDA shut spending. But insurers are no longer the “free and MultiCore combinatorial chemistry down the company’s studies in HPV-associated ride” for companies that they used to be, says technology to discover small molecules for cancers after Advaxis submitted a safety report Mani. Traditionally they have been reluctant the treatment of chronic pain, including regarding a cervical cancer patient treated with to apply the kind of cost savings seen in the neuropathic pain. Other financial details of the axalimogene filolisbac in 2013 in an investigator- public sector, but they are now starting to voice collaboration have not been disclosed. sponsored clinical trial. The woman’s blood tested concerns about the cost of some drugs. Specialty positive in July for Listeria monocytogenes (Lm) – drugs account for 2% of claims, but 26% of drug Indian Contract Manufacturing: the bacteria that the company uses in its vaccine spending, according to the 2014 Drug Trend Prospects And Pains candidates to induce an immune response Report from Express Scripts, Canada’s second Is the general uptrend in India’s contract against cancer – when she was admitted to the biggest PBM (pharmacy benefit manager, which manufacturing segment sustainable, despite some hospital for end-stage cervical cancer symptoms. adjudicates claims). One big insurer, Manulife, sentiment-dampening run-ins with regulators over says it is concerned about the increasing number compliance concerns? Yes, if a clutch of industry Roche’s Tchoumi On Selling of high priced drugs entering the market, and experts are to be believed. These experts also Cancer Drugs In EMs it wants to start a debate about whether “more underscore that firms that “follow” clients’ molecules Maturin Tchoumi, managing director of Roche expensive drugs generate sufficient additional across discovery and development all the way (India) Private Limited, leads the company at health outcomes to justify the higher cost”. It cites to manufacturing are likely the ones who have a time when drug pricing is a highly sensitive as an example Amgen’s anti-cholesterol PCSK9 an edge. Earlier this year, the Indian credit rating topic, thanks to Turing’s headline-grabbing inhibitor Repatha (evolocumab), which it says can agency CARE Ratingssaid that it expected the Indian price gouging act and subsequent retraction. cost up to $CDN7,300 per patient per year. “That’s contract manufacturing segment to grow at a While all eyes are on the differential pricing 80 times the cost of the generic version of the compound annual growth rate of around 17-18% structure for Roche’s just launched anticancers cholesterol drug Crestor. When you consider that till 2018. Navroz Mahudawala, managing director Kadcyla (trastuzumab emtansine) and Perjeta about 40% of all Canadians between the ages of of Candle Partners, a boutique investment banking (pertuzumab) in India, Tchoumi, in an interview 40 and 59 have unhealthy levels of cholesterol, firm, told Scrip that the current growth rates were with Scrip, refers to how Roche’s partnership with the scope of the financial impact grows,” it says. “definitely sustainable” for next four-five years as they the local firm Emcure has led to a “significant are still on a low base. He maintained that Indian increase” in the number of people able to access Biogen’s Kingsley To Blame firms in the space such as Dishman Pharmaceuticals oncology drugs in India. Roche’s “The Blue For Tecfidera Sales? and Chemicals Ltd, Syngene International Ltd Tree” programme for its oncology portfolio and The timing of Biogen’s Oct. 9 announcement that and Piramal Enterprises Ltd are still generally pipeline drugs is also expected to move the Tony Kingsley, executive vice president of global small compared with their global counterparts access needle, he indicates. Roche, which has commercial operations, is leaving the company and the low-base effect would make the growth had its share of pricing flak in this part of the came at an unfortunate time – just weeks before sustainable. Dishman recently disclosed that it holds world, some years ago pared prices and expanded third quarter earnings will reveal whether Tecfidera a license agreement from Janssen to produce the access to products like Herceptin (trastuzumab) (dimethyl fumarate) sales are growing, stable or active pharmaceutical ingredient (API) of Sirturo via a second brand program in partnership with sliding. Biogen’s stock ended the day down 3.8% at (bedaquiline). Others like S V Veerramani, president Emcure. A financing scheme, where patients can $269.16 per share, which is the company’s lowest of the Indian Drug Manufacturers’ Association, potentially stagger payments for medicines, is also closing price of the year, as investors and analysts recently said that growing contract manufacturing now on the cards for certain Roche anticancers. wondered whether Kingsley’s departure – either industry could also provide a “burgeoning” Tchoumi also underscored the need for greater voluntarily or at the request of his employer opportunity for small and medium-sized enterprises. regulatory transparency in emerging nations. This, – is a sign that sales for Tecfidera and the rest especially in view of the shift from the model of the company’s multiple sclerosis franchise Advaxis Sinks On Delayed of products being approved first in developed continued to disappoint in the third quarter. Disclosure Of Clinical Hold markets to one, as in the case for biosimilars, Tecfidera quickly became a blockbuster drug Advaxis Inc. fell 25.8% in after-hours trading where within certain emerging markets, and Biogen’s top-selling product with $883.3m on Oct. 6 when the company said the US FDA companies are able to apply for local or regional in sales during the second quarter of 2015 when placed a clinical hold on its investigational new approvals long before they submit data to the the company declared that it was the top-selling drug (IND) application for axalimogene filolisbac authorities in developed markets. oral MS therapy in the US. Even so, sales this (ADXS-HPV) – a disclosure that was made five year have come in below analyst consensus and days after Advaxis received word from the agency. Get Ahead In Canada’s Private Market investor expectations, and the sales growth rate The clinical hold affects four ongoing clinical trials Canada’s private pharmaceutical market is a has slowed as cases of progressive multifocal for the Princeton, New Jersey-based company’s big and growing opportunity for companies, leukoencephalopathy (PML) have been reported in therapeutic vaccine for cancers caused by the but taking a piece of the pie is not as easy as it MS patients treated with the drug.

10 October 16th 2015 @scripnews scripintelligence.com © Informa UK Ltd 2015 headline news Spark Restores Vision In PhIII; Hopes To Lead Gene Therapy Spark Therapeutics is preparing to seek the delivered via adeno-associated virus (AAV) first-ever US FDA approval for a gene therapy vectors. The gene therapy has a breakthrough after several people who couldn’t read a therapy designation from the FDA for the menu in a dimly lit restaurant or take a walk treatment of IRDs. alone at dusk had their vision restored in a Phase III clinical trial testing SPK-RPE65. Approval Plans, Pricing Two-thirds of the 21 people with RPE65- Spark is speaking with the FDA and ex-US mediated inherited retinal dystrophies regulators about submitting applications for (IRDs) who were treated with SPK-RPE65 in a marketing approval. The company will narrow 31-patient Phase III trial derived the maximum its guidance regarding the timing of those possible benefit that could be measured filings to specific timeframes in 2016 and polygraphus/shutterstock.com by the study’s primary visual function test – beyond following those discussions. navigation of a mobility course under lighting While it would be quite a feat for Spark to levels ranging from a moonless summer night win the first-ever FDA approval for a gene (one lux) to a brightly lit office (400 lux). Spark therapy, Marrazzo noted that SPK-RPE65 plans to submit a biologic license application would also be “the first pharmacological (BLA) in 2016 and CEO Jeffrey Marrazzo hopes treatment in an inherited retinal disease. the company will be a leader in its field when Patients don’t care if it’s a gene therapy, they it comes time to price the gene therapy. just want to get better.” Philadelphia, Pennsylvania-based Spark would’ve qualified for the Phase III study, we Payers are more likely to care about the traded as high as $74.93 per share on Oct. have followed them for two to four years mode of delivery for Spark’s treatment, since 5 – a 70.6% gain over its Oct. 2 closing price and the benefits have been maintained the US doesn’t have a model on which to – after the company revealed top-line results in the mobility test and light sensitivity,” base pricing for a gene therapy. Marrazzo and noted that it will provide additional Marrazzo said. said the company has done some market details from the pivotal trial at upcoming research and has been speaking with payers medical meetings. However, the stock about pricing and payment models for ultimately closed 20.7% higher at $53.02 on a ‘My goal is to be in on SPK-RPE65, but it’s too early to speculate day when the Nasdaq gained 1.56%, but the the discussion about how we on what the therapy’s pricing will be and Nasdaq Biotechnology Index fell 0.68%. whether treatment will be paid for in a lump create a payment model for a sum fee or a payment over a certain period Phase III Data of time. With its Phase III data and plans for a 2016 BLA one-time treatment’ “It may be a long-lasting or a one-time submission, Spark’s SPK-RPE65 development treatment. Patients gain function back and program remains on the schedule revealed at Spark’s gene therapy achieved statistical they do not have to get treatments over the start of 2015 when the company began significance for two out of three of the Phase and over again. It has the potential to be its campaign for an initial public offering. Now, III study’s secondary endpoints: full-field extremely meaningful to patients and their Spark’s stock is trading 130% higher than light sensitivity threshold testing (p<0.001) families,” he said, noting that about 3,500 its $23 IPO price as the company begins to and mobility test change score for the first people in the US and the five largest EU share data from its Phase III program to treat injected eye (p=0.001). SPK-RPE65 did not markets suffer from vision loss due to a IRDs caused by mutations in the RPE65 gene, show a significant improvement in visual mutation of the RPE65 gene. which initially leads to “night blindness” and acuity (p=0.17), which was expected based Based on the functional improvement for eventually results in total loss of vision. on prior studies and the effect that RPE65- people who’ve received SPK-RPE65 to date, “This is a degenerative disease, so people mediated IRDs have on vision loss. Marrazzo noted that Spark will “continue work are getting worse. We didn’t just stop their “This is a disease that is affecting light on pricing and accelerate those discussions vision from getting worse, we gave them sensitivity and peripheral vision rather than we’ve had with payers, looking at how we back function,” Spark Therapeutics co-founder central vision,” Marrazzo said. measure the benefit and what value it brings and CEO Jeffrey Marrazzo said in an interview Spark picked its Phase III endpoints based to families.” with Scrip. on guidance from the FDA, but added But a larger question looms: What is SPK-RPE65 met the Phase III primary visual acuity – a measure of central vision the most appropriate payment model to endpoint by showing a statistically significant – as a secondary endpoint, because some accelerate and encourage investment in improvement from baseline at one-year patients in earlier studies gained letters on potentially curative gene therapies and after treatment in terms of improvement of the standard eye exam chart. Patients in the incentivize their development rather than functional vision as measured by the change Phase III study, who ranged in age from 4 to lifelong treatment with prescription drugs? in bilateral mobility testing for 21 patients in 44, also had improved visual acuity, but the “My goal for this company is to be on the the clinical trial’s intervention group versus 10 difference between the intervention and leading part of this discussion of how we patients in the trial’s control group (p=0.001). control groups was not statistically significant create a payment model for a treatment that “Part of the data to be released in the or clinical meaningful. is one-time treatment. I think it’s important future shows the improvements we saw at The company reported no serious adverse that people focus on that payment model each of the time points over that year. In the events or deleterious immune responses for piece as much as pricing,” Marrazzo said. second Phase I study we ran, in subjects that patients treated with SPK-RPE65, which is [email protected]

© Informa UK Ltd 2015 @scripnews scripintelligence.com October 16th 2015 11 headline news Who Will Get First AD Drug To Market In Over A Decade? Analysts’ current impressions are that Axovant managed to gain a strong amount encenicline has the better data. of investor support for its only pipeline candidate in June when it raised a massive GSK Cast-Off $315m through an initial public offering; this Axovant, a wholly owned subsidiary of year’s biggest biotech IPO so far in terms of Roivant Sciences, picked up RVT-101 from money raised. GlaxoSmithKline for just $5m, via a licensing Daniel Chancellor, lead analyst at agreement, in December 2014. At the time, Datamonitor Healthcare, said investors were some saw this as GSK losing faith in the buying into this drug because “the general product, which in July 2011 reported poor sentiment around Alzheimer’s disease R&D is results in two failed six-month trials. Both of much more positive compared to a couple of these trials missed their primary endpoints years ago.” of significant improvement in cognition. GSK He added, “Axovant will sink or swim based Lightspring/shutterstock.com determined the product didn’t warrant the on this drug, but then the company was R&D spend required to take it to market. only created because of the opportunity to However, others believed the drug just in-license the product for a low price.” fell afoul of cost-cutting. It has since shown statistically significant results in Phase II and Phase III Details has shown stronger efficacy data overall On Oct. 6, the FDA agreed to a Special than its biggest competitor, Lundbeck’s Protocol Assessment (SPA) supporting idalopirdine. Axovant’s Phase III program for RVT-101, Alzheimer’s disease (AD) drug developer In Phase II, an analysis of all patients with providing further backing for the drug’s Axovant Sciences, which earlier this year raised complete data at each study visit showed promise in AD. a record-breaking sum of cash, has launched that patients receiving 35 mg RVT-101 The 24-week Phase III MINDSET trial will a large Phase III study for its 5-HT6 receptor in combination with approved, generic compare 35 mg, once-daily oral doses of antagonist, RVT-101– a move it hopes will set therapy donepezil demonstrated significant RVT-101 to placebo in approximately 1,150 the company up to seek the first approval for improvements in cognition and function at 12, patients with mild-to-moderate Alzheimer’s any new AD product in over a decade. 24, 36, and 48 weeks, compared with patients disease on a stable background of donepezil The 5-HT6 class has been an active space receiving donepezil alone. But analysts at therapy. The primary efficacy evaluations for Alzheimer’s research – a notoriously tricky Sagient Research’s BioMedTracker noted the are the Alzheimer’s Disease Assessment area of with a high margin for failure – with Phase II data showed that the effects of RVT- Scale-cognitive subscale (ADAS-cog) and a number of pharmas getting products into 101 were only modest on cognition. the Alzheimer’s Disease Cooperative Study- larger clinical trials. However, they said “even mild improvement Activities of Daily Living scale (ADCS-ADL), H. Lundbeck A/S has been leading the way on top of stable donepezil treatment would each of which have been used as endpoints with its offering, idalopirdine (Lu AE58054), fill a large unmet need.” The analysts added, to obtain regulatory approval of currently- which is in Phase III; while Pfizer Inc. and “We believe that replication of this Phase marketed AD treatments in the US and Suven Life Sciences also have 5-HT6 receptors II trial using the ADCS-ADL and ADAC-Cog Europe, Axovant noted. The study is being in Phase II for the treatment of AD. AbbVie is endpoints could very well lead to approval.” led by Axovant chief development officer Dr. a bit further behind with a Phase I candidate Based on the Phase II results, BioMedTracker Lawrence Friedhoff, who previously headed (see table). increased its likelihood of approval rating for the development program for donepezil (Eisai RVT-101 by 5%, to 20%, which is 3% above Co., Ltd /Pfizer Inc.’s Aricept, approved in 1996), First New AD Drug? average for a similar product at the same the most widely used Alzheimer’s treatment. If successful in Phase III, Axovant intends to stage of development. [email protected] submit a new drug application to FDA by the end of 2017. But it will be fighting for first- 5-HT6 Receptors In Development to-market status for this class of AD drugs against Lundbeck’s product. Originator Company Partner/ Licensee Product Stage of Development It will also be competing to be the title of GlaxoSmithKline (discontinued) Axovant (ongoing) RVT-101 Phase III “first AD therapy in over a decade” against Lundbeck Otsuka idalopirdine Phase III Forum’s encenicline, which is also entering Phase III. Encenicline, a partial agonist of Suven Life Sciences None SUVN-502 Phase II the alpha-7 nicotinic acetylcholine receptor, Pfizer None PF-5212377 Phase II saw positive Phase II data in which the 2 Roche Holdings AG (discontinued) BioTie Therapeutics (ongoing) SYN120 Phase I mg dose of the drug improved ADAS-cog Abbott AbbVie ABT-354 Phase I scores by 2.2 points over 23 weeks in “add-on” patients stable on ACheI therapies and “de AllaChem None AVN-101 Phase I novo” patients who had never taken or had AllaChem Avineuro AVN-211 Preclinical previously taken but were not currently being Suven Life Sciences None SUVN-507 Preclinical treated with AChEI therapies, donezepil or rivastigmine. Suven Life Sciences None SUVN-512 Preclinical

12 October 16th 2015 @scripnews scripintelligence.com © Informa UK Ltd 2015 headline news Meet The Company Giving Patients Access To Unlicensed Medicines There is a big unmet need around the A good example of that is in the US, where products. How you manage access to these ethical management and supply of you can look at the ‘Right to Try’ legislation products has to be done in a very ethical and unlicensed medicines. Their unlicensed and the 21st Century Cures Act which were controlled way to try and mitigate the risk of status could be due to the products still been passed recently. The FDA and the US counterfeit or unsuitable substandard drugs being experimental, or that the products government have realized that they can’t entering the supply chain. have been approved in certain territories stand against this anymore and need to but not others. And as patients and their engage in the debate and find workable SV: So who predominantly drives physicians become increasingly demanding solutions. And that’s just one example. Clinigen’s business activities? Patients or about access to hard-to-get medicines, pharma companies? a trend which is expected to continue, SV: You recently signed a managed access SC: Fundamentally with the supply of pharma companies understand they have program for an investigational ALS unlicensed medicines, it is the unmet medical a responsibility to work with physicians therapy with Neuraltus Pharmaceuticals. need highlighted by physicians in treating to enable access. And companies such How does this fit into the situation that their patients who have exhausted all licensed as Clinigen are there to help. Scrip’s news you describe? treatment options that is important here. With editor Sukaina Virji spoke to Clinigen’s SC: The Neuraltus partnership and other the managed access side, it’s predominantly deputy CEO Shaun Chilton. similar agreements are being driven by more from the pharmaceutical company because informed patients who are going to their they are at a very important stage of Sukaina Virji: Why is there an unmet need physician and saying, ‘OK, I’ve got this disease. development with their product. They do in unlicensed medicines? You’ve diagnosed me. I’ve done my own [managed access] for a couple of reasons. Shaun Chilton: There is quite a startling research online and accessed clinicaltrials. One, physicians are becoming more and more statistic: around 80% of the world’s population gov and talked to patient forums, and I’m connected and so in these niche areas, key doesn’t have access to the medicines they much more aware of what’s out there and opinion leaders, the investigators of the big require. Partly this is because of the changing what’s in development, and what’s available trials, and people running investigator initiated commercial model of pharma. Pharma no in different parts of the world that I can’t get studies talk to each other at conferences and longer does the big bang global launch to access to.’ Patients are increasingly saying they know what’s in development; it gets them tens of countries and for broad indications. It to their physician: ‘You’ve tried everything thinking. So when they’re treating their patients is a very much more targeted launch process else, and I want to be part of managing my who have these rare diseases, mostly oncology now: the major developed pharma markets own treatment, and I have a view – rightly or or infectious disease conditions, the difficult and relatively narrow indications and then the wrongly – on the types of treatments available.’ to treat cases, and when they have exhausted life cycle is managed from there in terms of We can help respond to that in two licensed therapies, they are aware that there is progressive launches expanding indications ways. With managed access, we work with another avenue, a legitimate ethical avenue, to based on increasingly real world data, and pharmaceutical companies of all sizes to access new innovative medicines. So they will only then if there is real commercial benefit manage – in a controlled way – early access often petition the pharma company. coupled with unmet or underserved patient of those more innovative experimental drugs. But it’s also in these pharmaceutical need. Clinigen does not say ‘Drug A is better companies’ interests because, at that pre- than Drug B and more appropriate for your launch stage, it is a great opportunity for the SV: How do regulators feel about the patients.’ The decision that, ‘Every opportunity opinion leaders and the treating physicians supply of unlicensed medicines? to prescribe a licensed medicine has been to get as familiar as they can with these new SC: What’s becoming increasingly obvious exhausted and I now have to look at innovative medicines. That works both ways: is that the regulators on one side and experimental medicines or medicines that aren’t the treating physicians get more familiar, and physicians and patients on the other side available in my country in the best interests of ultimately are able to treat patients in a more are now almost meeting in the middle. The my patient,’ is very much made by the physician. effective way, and also they are able to feed regulators understand that there is a need We then work with the pharmaceutical back to the pharma company how they are to manage the supply of medicines on an company to make that product available in a using the drug and how they are finding the unlicensed basis. They also understand that controlled and ethical way, often free of charge. use of that drug. With the rise and importance it is not commercially viable for pharma of real world data, what’s becoming more and companies to have a marketing authorization SV: So pharmaceutical companies are more obvious is that the traditional clinical trial with a sales force and medical support or actually providing a valued service here? setting – certainly the big multicenter clinical some sort of activity on the ground in every SC: There are good reasons why it’s an trials – is starting to die as a useful model of single country. And patients and patient ethical and important service that a particular what a drug is going to do in patients when it advocacy groups, not just in the US but in pharmaceutical company offers an unlicensed gets out into the real world. Hence you’ve got other parts of the world, particularly in rare medicine. this rise in the desire to capture and manage diseases and oncology, are much more The other end of the spectrum is that in real world data as a way of much more informed and are much more vocal about lots of markets, not just developing markets effectively commercializing products. their desire to access medicines, irrespective but even relatively mature markets, there [email protected] of what politicians say and irrespective of are lots of products that have never been what regulators historically have tried to do to made commercially available for one reason This article can be read in full at manage this area. or another and they can be quite mature http://bit.ly/1ZxIBNR

© Informa UK Ltd 2015 @scripnews scripintelligence.com October 16th 2015 13 R&D bites R&D Bites (MACE)-free survival for all patients in a Phase II a plenary session on Monday, Oct. 12. Amgen trial studying myocardial regeneration. The trial reported its first top-line Phase III results in studied 11 patients at high risk of incomplete September for romosozumab, a sclerostin inhibitor vascularization (ICR) undergoing coronary artery that the company is developing in partnership with

Alexander Raths/shutterstock.com bypass graft (CABG). The Waltham, Massachusetts- UCB, after Radius shared top-line Phase III data in based company plans to submit applications for December and June for abaloparatide, a synthetic US FDA and European Medicines Agency (EMA) peptide analog of the bone-building hormone approval by the end of 2015. In its BioMedTracker known as human parathyroid hormone-related database, Scrip affiliate Sagient Research forecasts protein (hPTHrP). The Waltham, Massachusetts- FDA approval for abaloparatide in mid to late based company plans to submit applications for 2016 and for romosozumab in March 2017. The US FDA and European Medicines Agency (EMA) Heartcel trial investigated a new regenerative cell approval by the end of 2015. In its BioMedTracker type, the allogeneic iMP cell (immuno-modulatory database, Scrip affiliate Sagient Research forecasts cell), as an adjuvant to mitigate the mortality FDA approval for abaloparatide in mid to late 2016 Alkermes Schizophrenia and morbidity associated with ICR. iMP cells are and for romosozumab in March 2017. mesodermal progenitor cells, an off-the-shelf Drug Wins FDA Nod cardiac specific cell type specifically engineered FDA Loves Opdivo: Another Quick Nod After the US markets closed on Oct. 5, Alkermes to regenerate the areas of the heart damaged by Richard Pazdur, director of the FDA’s Office of plc revealed it had gained the FDA’s approval heart attack or heart failure. All of the patients in Hematology and Oncology Products, obviously is to market Aristada (aripiprazole lauroxil) the trial, all suffering from advanced heart failure, in love with Bristol-Myers Squibb Co.’s programmed death-1 (PD-1) immune checkpoint inhibitor extended-release injectable suspension as a are still alive after an average of 28.4 months vs. up to an expected 70% annual mortality rate, and Opdivo (nivolumab) – granting the drug another treatment for schizophrenia. Shares of the none has suffered cardiac events such as heart remarkably fast approval. On Oct. 9, the FDA company rose 6.4%, or $3.86, in after-hours attack or stroke. If approved for CMA use, Heartcel expanded Opdivo’s use in metastatic non-small- trading on Oct. 5. Alkermes said its drug, would be the first cardiac-specific regenerative cell lung cancer (NSCLC) in patients whose which it plans to launch immediately, is the therapy approved for use in Europe and US. disease has progressed on or after platinum-based first atypical antipsychotic with once-monthly chemotherapy. The approval is for squamous and six-week dosing options for delivering and Can Genocea Build A Market? and non-squamous NSCLC patients. Regulators maintaining therapeutic levels of medication in Genocea Biosciences is one step closer to moving noted the drug’s earlier approval in NSCLC was in the body through an injection. That flexibility its lead candidate into Phase III, but despite positive the squamous population only, specifically, those meets the “real-world needs” of patients with results, there may not be a strong market for the whose disease had progressed during or after drug. Unlike the buzz around immunotherapies in platinum-based chemotherapy.That initial NSCLC schizophrenia, said Elliot Ehrich, chief medical oncology, Genocea has not been able to harness nod for Opdivo came from the FDA on March officer at Alkermes. The FDA approved that excitement for its non-cancer immunotherapy. 4 – more than three months before its June 22 Aristada based on data from a randomized, The Massachusetts biotech announced Oct. 7 that Prescription Drug User Fee Act (PDUFA) action date, double-blind, placebo-controlled Phase III it has achieved statically significant results in its which had Evercore ISI analyst Mark Schoenebaum study in 623 patients with schizophrenia, primary endpoint six months after administration for declaring it was the “fastest approval I’ve seen in which demonstrated the drug, at multiple GEN-003 in a Phase II trial. GEN-003 is a therapeutic my 15 year career.” Pazdur in March acknowledged dose strengths, met the primary endpoint with T-cell-directed vaccine against HSV-2, or genital his agency had worked “proactively” with BMS to statistically significant and clinically meaningful herpes. The drug is meant to reduce viral shedding – facilitate the early submission and review of “this reductions in positive and negative syndrome defined as when the active virus rises to the surface important clinical trial when results first became scale total scores at week 12. The trial also met of the skin and becomes contagious at the site of available in late December 2014.” infection, the primary endpoint of the study. The trial the key secondary endpoint and demonstrated also aimed to reduce herpes lesions, a secondary Novartis’ Narasimhan Bullish significant improvements in schizophrenia endpoint. Genocea said GEN-003 showed a 58% On Cosentyx symptoms versus placebo, Alkermes reported. reduction in viral shedding compared to baseline Novartis AG hopes new Phase III data showing The most common adverse events in the study and demonstrated sustained and statistically most patients were able to maintain clear or nearly were insomnia, akathisia and headache. significant reductions of skin lesions from baseline clear skin for up to three years by using Cosentyx in five of six dose groups ranging from 43% to (secukinumab) will reinforce and expand use of Cell Therapy Plots EU Conditional 69%. Approximately 30% to 50% of patients were its new plaque psoriasis treatment. The Swiss Approval For Heartcel lesion-free at six months after administration. The company already has first-mover advantage with Cell Therapy Ltd says that following a pre- therapeutic vaccine continues to be safe in patients. the drug, the first in a new class of medicines submission meeting with the European Medicines called interleukin-17A inhibitors, and is trying to Agency (EMA) in September, it now plans to begin Radius Ready To Face Off With Amgen establish Cosentyx’s lead in a tightly controlled applying for a conditional marketing authorization Conducting a large osteoporosis development reimbursement environment. The company (CMA) for Heartcel, its lead allogeneic stem cell program is a path that Amgen Inc. has been down thinks that aim will be helped by latest Phase III therapy, which has been designed to regenerate before, but it’s a make-or-break journey for Radius trial data in which 320 patients received Cosentyx the heart. Filing is planned for mid-2016, and, Health, which had one of the most successful initial in a fixed dosing schedule for three years. The if successful, approval could be granted as public offerings during the recent biotechnology extended study, the longest Phase III Cosentyx early as 2017. Cell Therapy’s CEO Ajan Reginald IPO boom based on optimism about its drug trial conducted so far, showed 69% achieved clear (previously Roche’s global head of emerging abaloparatide. Both companies will present or almost clear skin (PASI 90) at year one. That technologies) spoke to Scrip earlier this year in detailed clinical trial results for their osteoporosis response was well maintained after three years, detail about Heartcel and his company’s plans for therapies at the American Society for Bone and with 64% of patients continuing to have a PASI commercialization in Europe. In data published in Mineral Research (ASBMR) Annual Meeting from 90 response, while 43% of patients maintained June and September 2015, Heartcel demonstrated Oct. 9 to 12 in Seattle, Washington, and both completely clear skin (PASI 100) at year three, average two year major adverse cardiac event osteoporosis treatments will be highlighted in compared with 44% at year one.

14 October 16th 2015 @scripnews scripintelligence.com © Informa UK Ltd 2015 BEU15_SCRIPv2.pdf 1 10/2/15 10:35 AM

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Sanofi Builds Pharma Grapevine: Puppetry, Indian Sugar Clinics Pumping Iron And Patent Shoes Sanofi is pushing ahead with its sugar An occasional column in which we report If you’re keeping track, it seems that pharma clinics play in India in collaboration with amusing trivialities, pharmalicious gossip, just took one step forward and two steps back. the Apollo group – the first such effort biotech bons mots and other interesting anywhere in the world where the French observations picked up on our rounds. Puppet Master multinational is engaged with a leading Mylan has taken center stage as it continues healthcare provider. Reputation Alert: Transparency its pursuit and tender offer for generic Apollo Sugar Clinics Ltd (ASCL), in Rankings On Horizon drugmaker Perrigo, whose CEO Joe Papa has which Sanofi holds a stake alongside Big Pharma should probably brace itself for taken every opportunity to criticize Mylan’s India’s Apollo group, is an innovative, yet another assault on its public reputation. oft-brash management style. single specialty diabetes and endocrine The clinical data transparency campaign Papa’s comments have shone a spotlight healthcare service provider. AllTrials is preparing an audit of the top 50 on the dynamic between current Mylan CEO ASCL has now announced its debut big pharma companies and ranking them Heather Bresch and her predecessor, current in Mumbai with the opening of four according to their clinical data transparency executive chair Robert Coury. Industry insiders neighborhood care delivery centers, policies. The fact that some companies don’t and analysts have long thought of Bresch as taking its total tally up to 38 clinics across even have a policy on data transparency a puppet having her strings pulled by Coury, India. It expects to add an additional two in place is unlikely to help their ranking. who is still running the show. centers shortly. AllTrials has scored firms according to its gold It’s hard to argue that Bresch is more than “We promise to hand-hold Mumbaikars standard for registering trials and sharing just a glorified figurehead when all of the [people of Mumbai] in managing their results. The data have just been finalized and public correspondence between Mylan and diabetes by delivering proven and are being put together, Scrip has learnt. As the Perrigo has been exchanged between Papa internationally acclaimed standards of care only big pharma company that has signed up and Coury – showing pharma is still very at affordable price points, thus helping to AllTrials campaign, GSK may avoid public much an all boy’s club. improve their quality of life by preventing censure this time, but others will no doubt and reducing complications,” Gagan Bhalla, come under pressure to follow its example. Gandhi And Lithuania CEO, Apollo Sugar Clinics, said at a press The meeting with the Cipla patriarch was in briefing on Oct.7, in Mumbai. A Can’t-Win Situation For Pharma fact steeped in history. He had many interesting Mumbai has around 1.1m diabetics and Scrip recently attended the Interscience tales to share around the World War, India’s roughly half a million pre-diabetics and Conference of Antimicrobial Agents and freedom movement and Indo-Lithuanian an estimated INR4bn ($61.6m) is spent Chemotherapy (ICAAC) and International ties going back to the days of the friendship annually on medications for diabetes in Congress of Chemotherapy and Infection between Hermann Kallenbach, the Lithuanian the city, Bhalla said. (ICC) in San Diego, a joint conference born Jewish architect, and Mahatma Gandhi, ASCL claims to have interacted with co-hosted by the American Society for in South Africa. Apparently the Lithuanian more than 150,000 patients already. Microbiology and the International Society language has some similarity with India’s Sanofi’s collaboration is being tracked of Chemotherapy from Sept. 17 to 21, where Sanskrit as well. Indo-Lithuanian ties have now with interest by competition, with some we learned that sometimes big pharma just been further cemented with the unveiling of industry experts calling it the “next can’t win. a monument dedicated to Kallenbach and best step” to the French multinational Nicholas Kartsonis, Merck Research Gandhi, on Oct. 2 (Gandhi’s birth anniversary) integrating its operations vertically to Laboratories section head for antibiotics and in a Lithuanian village. The chair of the Indian control the entire value chain from point antibacterials, and associate vice-president of generic major – who was born to a Lithuanian of diagnosis to treatment, prescription clinical research in infectious diseases, touted mother in Vilnius – funded the monument and and sale of medicines, with the scope Merck’s deep portfolio in those areas, including attended its unveiling. of servicing a newly diagnosed patient bezlotoxumab for recurrent clostridium difficile across their entire life. infections, in an interview on Sept. 18 at the Unusual Pastimes Dr Shailesh Ayyangar, managing San Diego Convention Center. We all know that a work-life balance is critical Kartsonis noted that Merck’s antibiotic to good mental health, and we’re always keen director, India and vice-president, South portfolio may be deeper than its big pharma to hear how pharma and biotech executives Asia, Sanofi, told Scrip that in Apollo the colleagues, but that’s improving with unwind at the end of a busy week. We’re used company has a partner that “understands investments by Roche, AstraZeneca and others. to executives telling us about their reading care like nobody else..” He said, “This kind Meanwhile, in an interview later that same and jogging habits, so it was a refreshing of model doesn’t exist anywhere in the morning, an executive from a pre-commercial change to hear that the CEO of recent IPO world and it’s very important for us to antibiotic-focused biopharma firm lamented Cassiopea is a keen body builder. Can we learn as we go along.” the lack of big pharma interest in the field. swap our bingo wings for your triceps? India’s Apollo group is one of the Another biopharma executive feared that leading integrated healthcare providers in antibiotics acquired in recent big pharma Style Guru Asia. Apollo Hospitals, which started as a acquisitions of specialty pharma companies Never mind Elvis’s blue suede shoes. We prefer single 150-bed hospital, currently operates would be de-prioritized in favor of legacy the very shiny blue patent leather footwear around 9,200 beds across 64 hospitals. antibiotics or drugs in easier-to-sell, higher- sported by Karolinska Development’s new [email protected] grossing therapeutic categories. CEO, Jim Van heusden.

16 October 16th 2015 @scripnews scripintelligence.com © Informa UK Ltd 2015 policy & regulation briefs Policy & Regulation Briefs Supreme Court Must Act Fast praise from the Biosimilars Forum, which consists Biopharma Execs, On IPR Questions of a mixed bag of traditionally brand-name and Obama Go Face-To-Face With the unexpected popularity of the inter generic firms – Allergan, Amgen, Boehringer partes reviews (IPRs), the US Supreme Court must Ingelheim, Coherus BioSciences, EMD Serono, Over TPP move swiftly to determine whether the US Patent Hospira, Merck & Co., Pfizer Inc., Samsung, Sandoz President Barack Obama heard first-hand & Trademark Office (US PTO) Patent Trial and and Teva Pharmaceutical. Appeal Board (PTAB) is using the correct standard from a half dozen or so biopharmaceutical Exclusivity For Some TPP Countries executives during an Oct. 8 White House for the proceedings, the first company to bring such a case to the high court said in a petition Malaysia, Mexico, Peru and Vietnam would be face-to-face meeting about the industry’s filed this week. Cuozzo Speed Technologies permitted to have transition periods of five to 10 disappointment in the administration for LLC is contending that the PTAB should not years in implementing the biologic marketing agreeing to a minimum of five years of have applied the so-called broadest reasonable exclusivity rules agreed to under the Trans-Pacific exclusivity protection for innovator biologics interpretation standard in claim construction in Partnership (TPP), according to a document against biosimilars in the final Trans-Pacific its IPR, in which the board invalided one of the posted online on Oct. 9 by the anti-secrecy Partnership (TPP) deal rather than the 12 firm’s patents for obviousness. If the Supreme group WikiLeaks. But the Washington consumer years required in the US by law. Mark Grayson, Court takes up the case and decides the PTAB watchdog Public Citizen complained those spokesperson for the Pharmaceutical Research has been using the wrong standard, it potentially transition periods are “too short” to expect that those four countries will be “substantially more and Manufacturers of America (PhRMA), told could call into question the results of a number able to absorb the rules’ impact than they are Scrip that during the meeting, the biopharma of IPRs, said Washington lawyer William Jay, a partner at Goodwin Procter and a co-chair of today.” The TPP, whose negotiations officially executives emphasized to Obama the role the firm’s appellate litigation practice. IPRs are ended on Oct. 5 between the 12 nations involved “strong” intellectual property protection plays trial proceedings that were created under the – Australia, Brunei Darussalam, Canada, Chile, in the discovery and development of new American Invents Act of 2011 to be a faster Japan, Malaysia, Mexico, New Zealand, Peru, treatments and therapies, and that by “failing and more affordable alternative to litigation for Singapore, the US and Vietnam – has two options to secure” 12 years of data protection for challenging patents. for providing marketing exclusivity protection biologics, the next wave of innovation would for innovator biologics against biosimilars: At be compromised and the development Bar Against Glenmark’s least eight years from the date of first marketing of new critically-needed medicines would Sitagliptin Copies approval for the brand-name product or at least five years from the date of first marketing be disrupted. Interestingly, neither PhRMA The Delhi High Court has permanently enjoined approval with “other measures” and recognizing president and CEO John Castellani nor Glenmark Pharmaceuticals Ltd from making and selling its generic version of Merck & Co’s that market circumstances also contribute Biotechnology Industry Organization (BIO) diabetes therapies Januvia (sitagliptin) and to effective market protection to deliver a president and CEO Jim Greenwood were Janumet (sitagliptin/metformin hydrochloride). comparable outcome. Several of the TPP nations among the biopharmaceutical industry The Indian firm has been found to have infringed already have acknowledged the agreement leaders at the White House, the trade groups the sitagliptin patent. Justice AK Pathak, in an 133- does not require them to change their existing confirmed to Scrip. page order dated Oct.7, restrained Glenmark by biologic exclusivity rules, including the US, which a decree of permanent injunction from “making, has 12 years of protection under the Biologics Apotex: Amgen’s Biosimilar Lawsuit’s using, selling, distributing, advertising, exporting, Price Competition and Innovation Act – the 2010 A Sham offering for sale or dealing in sitagliptin phosphate law that gave the FDA the authority to approve Amgen’s patent infringement lawsuit filed in monohydrate or any other salt of sitagliptin in any biosimilars – and Australia, which has at least five August against Apotex involving its pegfilgrastim form, alone or in combination with one or more years. Currently, Brunei, Malaysia, Mexico, Peru and biosimilar, which is referenced on the former other drugs thereby infringing the suit patent No Vietnam have no marketing exclusivity protection company’s long-acting human granulocyte 209816 of the plaintiffs [Merck].” The suit patent is for innovator biologics. colony-stimulating factor Neulasta, is a “sham” essentially the sitagliptin Indian Patent No 209816 and part of an “overall predatory scheme to and has 20 claims. EU Ruling Turns Days Into €millions monopolize the relevant market,” the latter Just a few days could make a big difference for company charged in court documents filed this CMS Asked To Pause Payment Rule your company, perhaps millions of Euros. Thanks to week. In its answers and counterclaims, Apotex A group of 20 US senators on Oct. 8 asked the a ruling from the Court of Justice of the European said the lawsuit’s intent is to “delay, hamper, Centers for Medicare & Medicaid Services (CMS) to Union, some innovative products could have their hinder and impede” the company from entering postpone its proposed rule, which seeks to lump market exclusivity period extended in some EU the market with its pegfilgrastim biosimilar. biosimilars referenced on the same innovator into markets by a number of days or maybe weeks. Amgen’s “exclusionary, anticompetitive and the same Medicare Part B reimbursement rate, until This may not seem much on the surface, but it unlawful activities” threaten to damage Apotex by after the FDA has completed its regulations and could mean a windfall for the originator company “forestalling, frustrating and preventing” its ability the pipeline and the market for the products are and isn’t all bad news for the generics companies, to complete, the biosimilars maker contended. “safe and stable.” The agency in July said it planned explains Mike Gilbert, a partner at Marks & Clerk Apotex also said the lawsuit would cause it to to use a single average sales price payment limit Solicitors. The ruling centers around the way the suffer anticompetitive harm because it would for biosimilars that are assigned to a specific Austrian Patent Office had calculated the duration incur substantial litigation costs, and the mere healthcare common procedure coding system of a Supplementary Protection Certificate (SPC) filing of the litigation may deter customers from code – often referred to as J-codes for drugs. The awarded to Seattle Genetics’ Adcetris (brentuximab buying the pegfilgrastim biosimilar. The company CMS proposal would largely affect biosimilars vedotin). SPCs are important because they also inferred that the lawsuit may chill contracting of Amgen Inc.’s Epogen (epoetin alfa), Neulasta give up to five years’ extra market exclusivity to for the biosimilar product because of the fear of (pegfilgrastim) and Neupogen (filgrastim) – the compensate companies if it takes them more than a recall. “They don’t say that expressly, but that’s latter of which was the reference for the very five years to win regulatory approval from the date the implicit allegation,” said Boston lawyer Elaine first US approval of a biosimilar, Sandoz’s Zarxio they file their patent. Companies have to apply for Herrmann Blais, a partner in the intellectual (filgrastim-sndz), which won the FDA’s blessing on SPCs in individual markets and they kick in as soon property litigation group at Goodwin Procter LLP. March 6. The senators’ letter to Slavitt won quick as the patent expires.

© Informa UK Ltd 2015 @scripnews scripintelligence.com October 16th 2015 17 stockwatch Colors Of The Fall Something strange is happening in the stock market. What ended up as the best week of the year for the broad S&P 500 index was a down-week and month to date for the NASDAQ Biotechnology Index (NBI). This is not supposed to happen since the biotech sector is higher beta, meaning that if the broad equity index finishes the week up, the NBI should finish the week up more. paprika/shutterstock.com The underperformance of biotech last week and month against a positive broad market could be further evidence of the rotation of generalist investors away from the sector and while there was some positive news from pharmaceutical companies last week, negative news from deemed a second-tier or alternative test in had to drastically back-pedal in last week’s biotechnology companies could be coloring last week’s draft US Preventive Services Task disappointing pre-close announcement with the perspective of those investors with a Force colorectal screening guidelines. While expectations of flat annual Varithena sales decreasing tolerance to risk. the analysts at Jefferies were keen to point of about £1m. At this point, BTG’s analysts Shares of the world’s biggest gene out the negative commercial implications from Jefferies were probably trying to erase sequencing company Illumina, Inc. were of this event, back in the summer they from everyone’s memories their delusional in the red for most of last week after its cited Exact Sciences as their “top idea in $1.3bn “blue sky” estimates for Varithena. surprisingly negative third- and fourth-quarter diagnostics” after its R&D day, pre-announced Indeed, blood and plasma supplies company sales pre-announcement. The analysts at revenues of only $8.3m and Jefferies’ Haemonetics Corp. and prenatal testing Mizuho were quick to downgrade the stock underwriting of the $200m fundraising at company Sequenom, Inc. both re-affirmed while the analysts from Leerink Partners were $25.50 per share. The share price of Exact the link between poor financial performance basking in the glow of the previous week’s Sciences closed last week at $8.51. and pink-slipping their CEOs after significant pre-emptive downgrade, albeit for reasons One color that often accompanies the sales and earnings guidance revisions. unrelated to the weaker desktop instrument bursting of a biotech bubble is pink – as in At the very least, it appears that generalist sales that caused the preannouncement. the pink slips of workforce reductions. These investors who do not have a deep At the time of the Leerink downgrade, the have emerged in the last few weeks with understanding of the sector are taking profits analysts from Mizuho were quick to reiterate half the workforce (but not the CEO) going after a bull run in biotech that has lasted their “Buy” recommendation, citing Illumina’s at Verastem, Inc. after its Phase II failure, 25 nearly three years. There must however still be “robust demand’ and its ‘dominant position job losses plus the CEO’s retirement after many investors left in the sector who believe in a high growth market.” By contrast, the the mixed phase II results at Xenoport, Inc., that every small biotech company they invest analysts from JP Morgan were both consistent and most recently the retirement at the in has a billion dollar product, will be acquired and accurate in response to Illumina’s pre- request of the directors (which should in by big pharma and is immune from product announcement. Only bench-top placements future be known as an “Arexit”) of the CEO failure. Once the realization permeates that in Europe and Asia Pacific were weak, of Arena Pharmaceuticals, Inc. after the none of these assumptions is true, some whereas sales in the US and consumables continued dismal commercial performance investors are going to be left feeling very blue. across Illumina’s client base were as strong of its treatment for obesity, Belviq (lorcaserin). The Magna Biopharma Income fund as expected. These red quarters may be Workforce reductions in biotech normally holdings include Illumina. something investors have to get used to over come after a bubble has burst, rather than Andy Smith the rest of the year with the US dollar having during the process, as it probably takes a remained strong over the quarter and sales year or so for the board to start to worry Andy Smith is chief investment officer of Mann of any drugs or devices in Europe, Japan or about the number of years’ cash remaining Bioinvest. Mann Bioinvest is the investment China by companies reporting in US dollars on the company’s balance sheet. But if adviser for the Magna BioPharma Income are likely to show a similar weakness. As the the departures due to dismal commercial fund which has no position in the stocks analysts from JP Morgan pointed out, “the performances can occur at any time, then mentioned, unless stated above. Dr Smith gives long-term outlook remains unchanged” since there are some prime candidates who have an investment fund manager’s view on public (in my view too) the best positioned company long presided over the development of life science companies. He has been lead fund in personalized medicine and diagnostic- products for which, as is now becoming manager for four life science– specific funds, guided therapy is not a diagnostics company, obvious, there is no commercially viable including International Biotechnology Trust and but the biggest sequencing company. market. An example could be the recently the AXA Framlington Biotech Fund, and was By contrast, more traditional business honored CEO of BTG Plc, who has presided awarded the Technology Fund Manager of the models based on selling premium priced over much of the cost and the 19 years year for 2007. diagnostic laboratory and point-of-care it has taken to get its product Varithena tests seem even more likely to leave their (polydocanol injectable foam) to the For all Stockwatch articles visit investors in the red. Exact Sciences Corp.’s market. BTG’s CEO, who had previously scripintelligence.com/stockwatch Cologuard test to predict bowel cancer was predicted $500m in annual Varithena sales,

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SPONSORED BY SPONSORED BY SPONSORED BY SPONSOREDSOCIAL MEDIA BY SOCIALSOCIAL MEDIA MEDIA SOCIAL MEDIA SPONSOR SPONSOR SPONSOR expert view 3D Printing – A Brave New World For Pharma And Patents In the same way that railways and fast 3D Printed Drug Gets FDA Approval only licensed dispensation is taking place broadband access changed the rules on One specific advance in the sphere of bio and that the integrity of the final product where businesses could operate from, so too printing has recently made headlines, as the is consistent. Technology already in use for will 3D printing change the manufacturing FDA in the US this summer granted approval the 3D printing of consumer products may and distribution of tomorrow. It presents to Spritam (levetiracetam) pills, prescribed point the way to a solution. A number of enormous opportunity for small and to reduce epileptic seizures. The novel retailers already allow customers to customize medium businesses and perhaps a chance aspect to the approval was that the pill was items using in-store computers, for example for manufacturing to return on a larger made not with traditional compression or to select the color and finishes for some scale in the most developed economies. moulding techniques, but using 3D printing. products. In some cases, the customer can The accessibility of 3D printing promises to In producing pills in this manner, layer upon order in-store and have their chosen item(s) empower both businesses and individuals layer via a 3D printer, the manufacturer printed by their own 3D printer in their to create products which under traditional Aprecia has said that it can create pills which home; the CAD file being transmitted via an manufacturing processes would have perform better for patients by dissolving encryption service directly to the consumer’s been prohibitive both in terms of cost more rapidly, each pill being more porous as a home printer. If 3D printing technology is and logistics. For businesses of all sizes, result of the 3D printing technique employed. used for the dispensation of prescriptions the potential to decentralize production The benefit to Aprecia from the successful 3D without supervision, we can foresee similar holds exciting opportunities. With the printing of its Spritam product may go well systems needing to be adopted whereby first regulatory approval of a 3D printed beyond the claim to improved performance the commands would be transmitted to 3D prescription drug, a world of opportunity of the pills; the company’s website notes printers directly from the manufacturer on a presents itself for innovative pharmaceutical that it has acquired multiple patents over its score basis. companies. However, capitalizing on 3D 3D printing process and plans to file further Bespoke dosages: Linked to the possibility printing technology whilst retaining control applications in the future. for decentralized production is the ability to over intellectual property rights (IPRs) create bespoke dosages, rather than relying will be challenging and require a rethink Opportunities For Pharma on the traditional “one size fits all” approach. of traditional approaches both to patent Flexibility in delivery forms: Aprecia This has obvious benefits, not only for the drafting and licensing. claims that its use of 3D printing technology fine-tuning of dosages for different patients, has allowed it to optimize delivery for its but for facilitating treatment regimens which An Overview Spritam drug by achieving a more porous require variable doses over the course of The technology underlying 3D printing, often pill. Similarly, researchers have found that treatment. If prescriptions are being 3D known as “rapid prototyping”, has been in use the shape of delivery forms will affect the printed on site by doctors, creating bespoke for over 30 years. However, recent advances rate of release for a drug. Accordingly, we solutions for each patient would require no in 3D printing technology have seen it used may see increasing experimentation using more than a tweak to the instructions sent to for an expanding range of finished products, 3D printing techniques to create a variety of the printer. and importantly the price of printers and differently shaped pills which would be much production has reached a point of mass more difficult to produce using traditional Managing Risk uptake. The scale of the opportunity is only “tableting” processes. These changes in the realm of consumer now being uncovered. For example, a builder The ability to print in a variety of shapes products, and the availability and increasing in China has “printed” 10 homes in as many has also been noted for its potential to affordability of 3D printing, are not without hours. Military applications include the use assist in the delivery of medicine to children. issue. It could lead to an explosion of of 3D printed parts in the cockpit of RAF Children of varying ages and sizes have unauthorized goods being produced Tornado fighter jets. Astronauts aboard the different capacities for swallowing tablets, and sold for example. The technology for space station have 3D printed tools and and 3D printing could allow for tailoring of widespread, and potentially illicit, 3D printing replacement parts on demand. Consumer scale a wider range of sizes and shapes to meet of pharmaceuticals is not yet widely available, applications abound as well, with numerous their needs. but IPR holders should think about how best businesses offering “customizable” 3D printing Decentralized production: Whilst the to protect their rights, and limit liability, as the for certain products. Accessibility of 3D printers 3D printing of pharmaceuticals is only just technology develops. has grown, as so-called “maker spaces” have developing, it is clear that it may offer a myriad With the decentralized manufacturing appeared, not only in repurposed traditional of possibilities for reshaping the way medicines of illicit goods, identifying and pursuing copy shops, but also in public libraries. are delivered to patients. As with traditional infringers may be difficult, and costly. The “Bio printing” is a term which has been consumer products, 3D printing offers the traditional approach to the licensing of applied to the use of 3D printing techniques possibility to decentralize production. In the patents often grants an indemnity to the in the field of medicine, which has seen a future, we may see pills being 3D printed licensee promising the licensee exclusivity significant increase in activity. For example, onsite in pharmacies or hospitals, thereby to produce and sell a product. Yet imagine surgeons in the UK have implanted a 3D saving warehousing and transportation costs, granting such an indemnity and then printed cranium, and a cancer patient recently and reducing waiting times between patient discovering that there are large numbers of received a bespoke 3D printed rib cage. orders and supply. Some predict that patients small scale infringements via 3D printers. The Companies such as L’Oréal and Procter & may even print their medications on home 3D chasing down and stopping of multiple 3D Gamble are working to develop 3D printed printers one day. printing infringers could be a considerable human skin in order to reduce reliance on Before such fundamental change occurs, headache and very costly; not least because animal testing. though, our concern will be ensuring that at the smallest scale it may not be an

20 October 16th 2015 @scripnews scripintelligence.com © Informa UK Ltd 2015 expert view/headline news infringement in the legal sense. Yet the it from the rights holder, this would represent medicines may still be a number of years indemnity in your license agreement may a significant loss of revenue. away, innovators need to consider now how still require you to give compensation. Such Manufacturers and rights holders need best to protect their IPRs as 3D printing a scenario would be deeply troubling. So to be thinking what the future holds for technology continues to advance. with the increasing access to 3D printing them. Now is the time to work with their James Tumbridge and Robert Peake technology, licensors should consider the relevant trade bodies to consider how to scope of the indemnity offered to licensees. align their business models to the 3D printing James Tumbridge is the head of the intellectual opportunities and risks. Identification now of property and litigation department in Pillsbury Revenue Protection gaps in legal protections, before technology Law’s London office. He has extensive experience As the technology continues to evolve, 3D or its use progresses to the point of posing in commercial litigation, intellectual property printing will increasingly allow individuals a serious commercial risk, is the best course. and alternative dispute resolution (ADR). He is to reproduce products in their own homes, There is a clear lesson from the music industry also a qualified mediator, listed with the world and in many cases this will be done for their considering their initial reaction to online file intellectual property organisation (WIPO), the UK own personal use. Reproducing a patented or sharing. The first response was traditional legal Intellectual Property Office, ADR Group, IDRS, Talk design protected product, for purely private action to stop infringement but that proved Mediation, Clerksroom, and a number of other non-commercial use, will not constitute an costly and ineffective at halting the change ADR providers. infringement of a patent or design. Whilst in the market. Ultimately embracing paid-for this exception to infringement may not be of downloads and changing the approach to Robert Peake is an associate with the intellectual significant concern where the occurrences are business proved the solution. Will 3D printing property practice in the law firm’s London office. few, it is clear that that if 100,000 customers require the same changes from manufacturers? His practice covers a broad range of trade mark, were to 3D print a patent protected product 3D printing technology offers a wealth copyright and patent matters, with a particular using their own 3D printer instead of sourcing of opportunity. Whilst local 3D printing of focus on contentious proceedings. NHS Innovative Drug Scorecard Paints Unclear Access Picture Latest collected data of patient access in in England, the ABPI said its underlying interpret if it was ever to become a useful tool. England to recently launched drugs again message was blurred and “disappointing”. “We’re not apportioning blame to the shows low uptake of such therapies and Compared with expected usage, the use HSCIC, but this Innovation Scorecard is underscores the need for revamping the way of new medicines in the NHS in England is just too complicated and not at all user- modern medicines are made available to far lower than expected, the ABPI said in a friendly and thus of little practical use,” patients in the UK, according to the Association statement. said David Watson, director of pricing and of the British Pharmaceutical Industry. The new data also show there is still wide reimbursement at the ABPI. “It’s not easily The trade body was responding to regional variation between the medicines that searchable, and in its present form no one is the Oct. 1 publication of the so-called patients can access in some parts of England going to bother looking at it because no one Innovation Scorecard published by the compared with others. For example, in some can afford to spend days delving down into Health and Social Care Information Centre cases there is a twenty fold difference in the the data. We can. But it’s very complicated,” (HSCIC) which pulls together local data from use of some medicines between one area Watson said in an interview with Scrip. across the publicly-funded National Health team and another. The HSCIC in an email noted that there Service to show the regional provision of was no central collection of data to directly medicines and technologies approved by support the assessment of uptake of NICE the National Institute for Health and Care ‘Use of the latest recommendations, nor were data on the Excellence, or NICE. NICE-recommended medicines number of patients treated available for use in The scorecard, an experimental publication, compiling its Innovation Scorecard. makes use of data 4 from a range of sources, in the NHS continues to be ABPI’s Clough stressed that the Scorecard both from the NHS and the commercial was a valuable key tool in focusing debate sector. The first Innovation Scorecard was unacceptably low’ on improving patient access to NICE- published in January 2013, using data from recommended medicines in England. 2011. The second publication in September “It is disappointing that the new data shows “We welcome its publication and industry 2013 reported data for 2012. The Innovation that the use of the latest NICE-recommended fully supports the continued development Scorecard has since been published on a medicines in the NHS continues to be of metrics. We have worked closely with quarterly basis, showing data for additional unacceptably low. There is a particular issue with the Department of Health, HSCIC and other quarters since October 2013. Its aim is to the use of medicines in the first five years of their stakeholders to develop the Scorecard and improve transparency within the NHS of launch,” said Alison Clough, Acting CEO of the understand the limitations of data that currently what treatments recommended by NICE are ABPI. “NHS patients are not being allowed access exists in the system … We hope that the [UK] available within the health service in England. to treatments which could play a significant government’s Accelerated Access Review will The latest compilation covered 83 medicines transformative role in their care and therefore in address these barriers to patient use and help approved by NICE since January 2011. the outcomes they achieve,” she added. improve the adoption and diffusion of the While reiterating support for the scorecard’s The ABPI also said the Innovation Scorecard newest and most innovative medicines across aim of increasing transparency of drug usage needed to be made much easier to use and England,” she concluded. [email protected]

© Informa UK Ltd 2015 @scripnews scripintelligence.com October 16th 2015 21 US capitol capsule Advance Science, Don’t Pressure FDA On Approvals, Drug Chief Tells Advocates “Patient advocacy groups should be in Drisapersen and eteplirsen now are under Vertex Pharmaceuticals Inc. of Kalydeco the business of advocating for patients, review at the FDA, with decisions due Dec. 27 (ivacaftor), which was the first medicine in not advocating for specific drugs or and Feb. 26, 2016, respectively. the US, initially approved in 2012, to treat the development programs,” Janet Woodcock, But rather than demand the FDA approve underlying cause of CF. director of the FDA’s Center for Drug certain drugs, for which the agency cannot Had Vertex had to do the work on its own, Evaluation and Research (CDER), insisted reveal the reasons why it may not be able it would have “taken years and years,” she said. last week at the Biotechnology Industry to act more swiftly, Woodcock said it would Finally, Woodcock said, patients and their Organization’s 2015 Patient and Health be more useful for patients and advocates advocates can help define how meaningful Advocacy Summit in Washington. to turn their attentions to activities that will the benefit of a therapy is to someone with a “I don’t think it’s that healthy to engage move the translational medicine research for specific disease and at the different stages of patients and advocates for a drug,” Woodcock certain diseases forward – going beyond the that condition. told Scrip after the meeting. “That’s not traditional roles of supporting and funding “That is incredibly valuable information,” a useful activity in general,” she added, basic science research. she said. acknowledging she’d raised a “controversial” If patient advocacy groups are serious “Patients are positioned to provide the best issue at the meeting. about getting drugs across the finish line, assessment of the risk-tolerance for people Woodcock also said it would “not really Woodcock said they must first have a “pretty who have that disease,” Woodcock said. be helpful” to have a patient at every detailed understanding of the ecosystem and Patient groups also can work on getting meeting the FDA holds with manufacturers the players and the points you can intervene done the measurement systems, like scales, – something some patient advocacy groups, in” and be clear about the state of knowledge tests or algorithms, for determining risk- like FasterCures, have pushed for in recent that exists for their disease – what’s benefit trade-offs, she said, pointing out years – mostly because those get-togethers scientifically valid. that “without knowing their performance are “filled with jargon,” and it’s unlikely anyone Patient advocates, especially for rare characteristics, your trial may be just in the know is “going to be willing to stop and diseases, also can help define the natural completely worthless.” translate this into English.” history of a disease – what happens to people “FDA knows it needs to put out guidance “We are talking very technical stuff,” she and how fast and which problems progress on this,” Woodcock said, adding that the said in an interview. “I can guarantee you and at what rate, she said. agency plans to do so as part of its Patient- these meetings will not be understandable” “That’s a research contribution that patients Focused Drug Development program. to patients. groups are uniquely positioned to do and it But she said the agency is awaiting Plus, the CDER chief said, even though will be incredibly helpful if the time comes the funding to provide the resources to companies are permitted to bring a patient when there are drugs or other interventions accomplish that task – dollars that are with them to the meetings with the FDA, “a in the pipeline that need to be tested,” supposed to be coming as part of the single person does not represent all patients Woodcock said. House’s 21st Century Cures Act, although it’s with a specific disease. They represent one Patients and advocates also can support not known whether the Senate will include person with that disease.” scientific research on pathogenesis, she such a measure in its yet-to-be unveiled And, she pointed out, the FDA holds about said, but she also urged to “strongly make companion legislation. 2,000 meetings each year with manufacturers, sure there is rigor in that research” and due “Patients can make a huge difference in the so logistically, it would be “very difficult” to diligence is adequately performed, ensuring development of drugs or other interventions also have patients join in. there is accountability. for their disease,” Woodcock said. “But we need “I understand why people engage in In addition, Woodcock said, patient groups to provide you the tools because it can be a extreme advocacy techniques, because should be advocating for and organizing the bewildering area and you can get off course people are angry and frustrated,” she said. “But establishment of “centers of excellence” in the pretty easily and perhaps waste time and it doesn’t advance the science.” diseases for which they are interested and effort and money.” Woodcock said the FDA should be allowed study-ready cohorts. “We owe you those guidebooks, advice, to “objectively judge” a drug, “rather than listen “One of the big delays is finding the guidance on how to do this,” she said. to what people tell you about how great it is.” patients and enrolling them in a trial,” she Woodcock also urged patient groups, The FDA most recently has come under said. “Organized patient groups who can academic researchers and industry to fire by some patients and advocates for not use social media or other means to identify review and use the new recommendations moving quicker on BioMarin Pharmaceutical people out there with the disease, have released last week by the public-private Inc.’s and Sarepta Therapeutics Inc.’s Duchenne them referred to a center of excellence or partnership organization the Clinical Trials muscular dystrophy (DMD) drugs drisapersen treatment center, understand if they are Transformation Initiative for incorporating and eteplirsen. willing to enroll in a clinical trial and have the patient perspective into the drug Indeed, Duchenne advocates were even those people identified and ready can cut R&D process. successful last year in getting the FDA to years off development time.” [email protected] respond to a “We the People” White House Woodcock pointed to the Cystic petition, in which Woodcock personally Fibrosis Foundation as the “best example” responded, pledging that regulators were of accomplishing that feat – noting that For all Capitol Capsule articles visit “willing to explore the use of all potential the work it did early on led to the quick scripintelligence.com/capitolcapsule pathways” for therapies against DMD. development by the group and its partner

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

Late-stage clinical developments for the week 2-8 October 2015 Lead Company Partner Company Drug Indication Market Comments REGULATORY APPROVAL Alkermes plc – Aristada (aripiprazole schizophrenia US Aristada is an atypical antipsychotic with once-monthly and six-week dosing lauroxil) extended-release options for delivering and maintaining therapeutic levels of medication in the injectable suspension body through an injection. Alkermes is preparing to launch Aristada immediately. Novartis AG – Entresto (sacubitril/ congestive heart failure Canada For the treatment of heart failure with reduced ejection fraction in patients with valsartan), previously NYHA Class II or III, to reduce the incidence of cardiovascular death and heart known as LCZ696 failure hospitalization. Entresto was granted a Priority Review by Health Canada due to the positive nature of the results demonstrated by the PARADIGM-HF study. SUPPLEMENTAL REGULATORY APPROVAL Gilead Sciences – Letairis (ambrisentan) pulmonary arterial US For use in combination with tadalafil for the treatment of pulmonary arterial Inc. hypertension (PAH) hypertension (PAH) (WHO Group 1) to reduce the risks of disease progression and hospitalization for worsening PAH, and to improve exercise ability. Letairis is an endothelin receptor antagonist that was first approved in 2007 in the US as monotherapy for PAH to improve exercise ability and delay clinical worsening. REGULATORY FILING ACCEPTED Novartis AG – biosimilar etanercept psoriasis and rheumatoid US Sandoz, a Novartis company, announced that the FDA has accepted its BLA under (Sandoz) arthritis the 351 (k) pathway for its proposed biosimilar to Amgen’s US-licensed Enbrel (etanercept). Sandoz is seeking approval for all indications included in the label of the reference product which is used to treat a range of autoimmune diseases including rheumatoid arthritis and psoriasis. REGULATORY FILING Ultragenyx – aceneuramic acid ER (Ace- muscular dystrophy EU For aceneuramic acid prolonged release intended for patients with GNE Pharmaceutical ER; UX001) tablets myopathy. Ace-ER is designed to replace the deficient sialic acid substrate in Inc. patients with GNE myopathy, also known as hereditary inclusion body myopathy, a rare, progressive muscle-wasting disease. ORPHAN DRUG DESIGNATION Protalex Inc. – PRTX-100 immune EU Protalex announced that the EMA Committee for Orphan Medicinal Products thrombocytopenic (COMP) has issued a positive opinion recommending PRTX-100 for designation as purpura an orphan medicinal product for the treatment of immune thrombocytopenia. SPECIAL PROTOCOL ASSESSMENT AGREEMENT Axovant Sciences – RVT-101 Alzheimer’s disease US Axovant Sciences announced the first patients screened in MINDSET, a Inc. confirmatory global Phase III study of Axovant’s lead product candidate, RVT-101. Axovant also announced that the company and the FDA has agreed to a Special Protocol Assessment supporting this Phase III program. FAST-TRACK STATUS Merck KGaA Pfizer avelumab Merkel cell Carcinoma US Merck KGaA and Pfizer announced that the FDA has granted avelumab Fast Track designation for the treatment of metastatic Merkel cell carcinoma (MCC). This announcement builds on the recent FDA Orphan Drug designation that was granted for avelumab on Sept. 21, 2015, for the treatment of MCC. ACCELERATED/CONDITIONAL APPROVAL Merck & Co. Inc. – Keytruda (pembrolizumab) non-small cell lung cancer US As a monotherapy at a dose of 2 mg/kg every three weeks, for the treatment of (NSCLC) patients with metastatic NSCLC whose tumors express PD-L1 as determined by an FDA-approved test and who have disease progression on or after platinum- containing chemotherapy. PRODUCT LAUNCH DARA BioSciences Mission Pharmacal Oravig (miconazole) fungal infections US DARA BioSciences announced the US launch of Oravig, an orally-dissolving muco- Inc. adhesive buccal tablet approved to treat adults with oral thrush, into the oncology and primary care markets. Beginning this week, DARA and its marketing partner Mission Pharmacal Company will simultaneously begin promotion of Oravig with two separate sales forces focusing on the highest prescribing physicians of oral thrush therapy; DARA will promote Oravig exclusively in oncology with its 20 person nationwide sales force and Mission will utilize its 40 person-strong sales team to promote the product exclusively to the primary care market. Oasmia Pharmasyntez Paclical (paclitaxel ovarian cancer Russia Oasmia Pharmaceutical has shipped Paclical to Pharmasyntez, its distribution Pharmaceutical (micellar)) partner in Russia which is expected to commence sales efforts promptly. Paclical, a AB novel water-soluble formulation of paclitaxel, was approved in April 2015 by the Russian agency. Pharmasyntez is expected to market the product in Russia, Ukraine and Georgia as well as the Commonwealth of Independent States (CIS) countries. Source: BioMedTracker

Paratek Pharmaceuticals, Inc. has appointed Vedanta Biosciences has appointed Lisa Rae Dr. Squires was chief medical officer (CMO) at Regina Paglia senior vice-president of human Schopf head of preclinical development and Erick Lumos Pharma and prior to this she was vice- resources and Dr. Stephen Villano vice-president J. Spek head of intellectual property. Schopf joins president of R&D and ADHD business unit medical of clinical and medical affairs. Most recently Paglia Vedanta from Kala Pharmaceuticals where she was lead at Shire Pharmaceuticals. Dr. Fitts started his was vice-president of human resources at Myriant senior director of preclinical development and has career at SmithKline Beecham Pharmaceuticals Corp., a biochemical company. Villano brings over also previously worked at Virdante Pharmaceuticals, (SB) and more recently he was head of biometrics 20 years’ experience in antiviral and anti-infective Abbott Bioresearch Centre, Millennium and at ViroPharma. Dr. Spielberg has been dean of the research to Paratek and was previously vice- Genetics Institute. Prior to joining Vedanta, Spek Dartmouth Medical School, vice-president for president of clinical research and development at was director of IP at Epizyme, Inc. and before this he paediatric drug development at J&J and deputy commissioner for medical products at the US FDA. ViroPharma, Inc. Before this, he was medical director worked at Wolf Greenfield, an IP law firm. of virology, medical science and development at Fate Therapeutics has appointed Scott Wolchko Mina Therapeutics has appointed David Blakey Dupont Pharmaceuticals. president and CEO following Christian Weyer’s chief scientific officer. Blakey joins the company from resignation – effective Nov. 30, 2015. Wolchko, who AstraZeneca where he held various roles in R&D over Kevin Bain, who was recently Alvogen’s chief was chief financial officer (CFO) since the company 28 years. Most recently, Blakey was chief scientist in financial officer (CFO), has been appointed CFO of its was found in 2007 and chief operating officer oncology and before this he led the company’s first biotech sister company, Alvotech. He will continue since January 2013, has also joined Fate’s board collaboration in therapeutic antibodies with Abgenix. as executive vice-president of strategic development of directors. Prior to Fate, Wolchko was CFO of an at Alvogen where Graham Baker has been appointed enterprise software company, Bocada Inc. In addition Sucampo Pharmaceuticals, Inc. has named the new CFO - effective Nov.1, 2015. Prior to Alvogen, to Wolchko’s appointment, Dr. Daniel Shoemaker Timothy P. Walbert to its board of directors. Baker spent 20 years’ at AstraZeneca where he was has been promoted to chief scientific officer from Currently, Walbert is chair, president and CEO of most recently vice-president of finance for the chief technology officer; Dr. Stewart Abbot, formerly Horizon Pharma Plc. and prior to this he was CEO, company’s international business vice-president of translational research, has been president and director of IDM Pharma, Inc. which named chief development officer; and Cindy Tahl has was acquired by Takeda. Walbert has also previously Heron Therapeutics has appointed Neil J. been promoted to general counsel after being the served as executive vice-president of commercial Clendeninn senior vice-president and chief company’s senior legal counsel since 2009. operations at NeoPharm, Inc. medical officer (CMO). Clendeninn is currently a practicing physician and program director for Medgenics, Inc. has appointed Liza Squires Regen BioPharma, Inc., has appointed Dr. Harry Palliative Medicine Partners. He is also president vice-president of R&D, therapeutic area head of Lander as president. Lander brings extensive of his own consultancy firm CANDAID, Inc and neuroscience and David Fitts vice-president and experience as both a researcher and administrator was advisor to the company before joining Heron. head of statistical sciences and data management. to the company and has served in these positions Previously, Clendeninn also served as senior vice- Stephen P. Spielberg has also joined the at Cornell University and Sidra Medical and president and head of clinical affairs at Agouron Inc. company’s scientific advisory board. Most recently, Research Centre in Qatar.

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