Scrip Asks... IO Roundtable Expert View Do experts see orphan drug pricing Five companies talk about their place New products are set to shake the coming under pressure over the next in immuno-oncology (p10) hemophilia market – but convincing five years? (p4) payers will be a challenge (p14)

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Scripscrip.pharmamedtechbi.com Pharma intelligence | informa consultant to Sanofi; it gained steam when he joined Sanofi in his present position. “I structured the strategy for Sanofi in two phases. The first phase was how do we build a pipeline to be delivered in 2015, 2016, 2017 when we had loss of exclusiv- ity on key products, with Lantus being the last major drug after Plavix and others that lost their patents. The goal was how to do it without breaking the bank,” Zerhouni told Scrip in a recent interview. That initial revamp involved overhauling the pipeline and trimming 19 Phase II and Phase III programs from Sanofi’s R&D pipe- line between 2009 and 2012. Some of the programs missed Phase II endpoints. Oth- ers were discontinued because the value Elias Zerhouni proposition wasn’t there from either the patient or payer perspective. “I modified the strategy in a big way, by putting development first: we have to Sanofi R&D Chief Zerhouni: take care of development and underneath all that, start to fix research, not the other way around. Most heads of R&D, are heads How I’m Doing More With Less of R&D; I said, ‘No, I want to be a head of Elias Zerhouni says Sanofi’s ongoing R&D revamp has produced improved D&R,’ rather than R&D at Sanofi,” Zerhouni innovative results with controlled spending, in part by emphasizing cutting- explained. edge product development ahead of research. IMPROVED PRODUCTIVITY STEN STOVALL [email protected] The second phase of the revamp is focused on early research and is ongoing. anofi ‘s head of global research and by former Sanofi CEO Chris Viehbacher. Zerhouni says the pipeline turnaround development Elias Zerhouni feels the Remaining in that role under current CEO can already be seen in new drug launches. outside world – meaning analysts and S Olivier Brandicourt, Zerhouni has been “Between 2008 and 2012, Sanofi investors – have yet to fully appreciate the vigorously remolding the company’s early launched three drugs. Between 2012 and pipeline progress and future promise gener- and mid-stage pipeline so the company 2017 - provided we get FDA approval for ated by his ongoing revamp of the French can replace revenues lost from patent dupilumab at the end of this quarter that group’s R&D process, but he is confident that expiries for blockbusters like platelet anti- we hope for - we will have had 13 launch- will soon happen, helped by further expected aggregant Plavix (clopidogrel) and Lantus es. So, by numbers, it’s doing well,” Zer- success developing multi-specific therapies. (insulin glargine). houni said. He said that in terms of sales A native of Algeria, Zerhouni was ap- The initial R&D strategy revamp began for 2016, new drugs represented €2.7bn pointed to his current position in 2011 even earlier in 2009 when Zerhouni was a CONTINUED ON PAGE 7

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Breathing Room For Teva

What Next In Orphan Pricing? 3 4 How To Please Payers? 15

COVER / Sanofi R&D Chief Zerhouni: How I’m Doing More from the editor With Less [email protected] 3 Teva Catches A Break On Copaxone 40mg, But For How Long? In January Scrip reported on the launch of the new Coalition for Epidemic Preparedness Innovations, 4 Scrip Asks: What Will Happen Next In Orphan which aims to drive development of DNA/RNA- Drug Pricing? based vaccines against emerging infectious diseases, and reduce the risk of a new crisis like that of Ebola, 6 Chi-Med Roll Continues With Positive Fruquintinib which had languished in pharma R&D owing to a 8 Spring Break: Novo’s US Head Resigns After Rough Winter lack of commercial incentives. Now, a new index mapping how companies are 9 R&D Bites performing in driving access to vaccines in high-need 10 Roundtable: Immuno-Oncology 2.0 Roundtable: countries has been published by the Dutch non-profit Emerging Players Eye Crowded Field Access to Medicine Foundation, which has been producing the Access to Medicine Index since 2008. 12 UK’s Crackdown On Anti-Competitive Deals Continues The Access to Vaccines Index maps how eight key 13 Policy & Regulation Briefs companies are performing against 13 metrics, and the evidence shows they are doing a lot. The authors 14 Expert View: Hemophilia: How To Please Payers And suggest the index can help identify opportunities Secure Market Share to improve vaccines access, and where new incen- 16 Roche’s APHINITY Trial Boosts Outlook On Its tives are needed. In fact, it identifies the actions Oncology Business and omissions specifically of industry and does not explicitly propose external incentives. Companies 17 Juno Ends JCAR015 Development In ALL are expected to be morally motivated to do more, 18 R&D Strategy: WHO’s List Of Pathogen Threats To aided by the new benchmarking tool. Like it or not, Rouse Developers the gauntlet is thrown down, and the onus is now on major vaccines players to pick it up. 20 Business Bulletin 21 Exclusive Interview: Shire’s Wellhoefer On Genetic Disease R&D And Expanding Access To Medicines exclusive online content 22 Pipeline Watch 23 Appointments

Keryx Looks To Label Expansion To Drive Auryxia Keryx plans to expand Aurexia’s label to treat iron deficiency in pre-dialysis patients while searching for additional nephrology assets during 2017. http://bit.ly/2mMvaif

Beyond Belviq: Reinventing Arena To Focus On Phase II Candidates Dr. Amit Munshi, new CEO of Arena Pharmaceuticals, has already made several changes in the company’s focus and direction as it reduces its commitment to Belviq. He talked to Mike Ward about progress to date. http://bit.ly/2lwf0cw @scripnews /scripintelligence

/scripintelligence /scripintelligence

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Teva Catches A Break On Copaxone 40mg, But For How Long? An FDA warning letter cites deficiencies at the Pfizer-owned manufacturing facility poised to produce a Momenta/ Sandoz generic competitor. It’s unclear how long Pfizer might take to resolve the violations, which include particulates in finished products.

JESSICA MERRILL [email protected]

eva Pharmaceutical Industries Ltd. has gotten some breath- It’s not clear how quickly the problems might be rectified, but in a ing room with news that the launch of a generic rival to the same-day email to investors, Evercore ISI analyst Umer Raffat said the T important 40mg version of its blockbuster multiple sclerosis median time to resolve manufacturing issues on finished pharmaceu- drug Copaxone (glatiramer) has been delayed due to a manufactur- ticals is 13 months. He analyzed data over 20 years and found the mini- ing issue. mum time to resolution is five months and the maximum 47 months. An FDA warning letter, made publicly available Feb. 28, cites several He also pointed out that the letter was addressed to Pfizer CEO Ian manufacturing violations at the Pfizer Inc.-owned facility in McPher- Reed rather than a lower-level manager. “When FDA addresses the let- son, Kan., that was poised to produce the 40mg product on behalf ter to the senior most person, it is trying to make a statement,” he said. of sponsors Sandoz Inc. and Momenta Pharmaceuticals Inc. The two drug makers had been planning to launch the generic imminently after a district court invalidated several patents protecting the newer formula, which is administered three times a week, rather than every day like the older 20mg formula. Momenta announced a delay in the launch Feb. 21 because of the manufacturing violations, but didn’t offer many details on the contents of the letter. CEO Craig Wheeler said at the time the company was still hopeful the launch could occur in 2017. For Teva, the delay is a positive turn at a pivotal time, when the Is- raeli drug company is facing backlash from investors over slow generic growth, an expensive merger and the disappointing patent ruling. The ongoing challenges have resulted in two high-profile leadership de- partures at Teva: former CEO Erez Vigodman, who left the company in February, and generics head Sigurdur (Siggi) Olafsson, who stepped down in December. The company has appointed an interim CEO, Yitzhak Peterburg, while it searches for a fulltime replacement and Shutterstock: Alextype Shutterstock: conducts a thorough business review. Teva issued financial guidance in January forecasting a revenue re- Other drug manufacturers also pose a threat to Teva. Aside from duction of $1bn to $1.3bn in 2017 if one or two generic competitors Sandoz/Momenta, several other generic drug manufacturers also to Copaxone 40mg were to hit the market. Sandoz/Momenta already have ANDAs at FDA pending for the 40mg Copaxone dose, including market a generic version of the once-daily version of Copaxone called Amneal Pharmaceuticals LLC, Dr. Reddy’s Laboratories Ltd., Mylan NV Glatopa, which the Pfizer plant has been producing for commercial and Synthon Pharmaceuticals Inc., which is partnered with Pfizer on use since April 2015. Teva’s success transitioning patients to the 40mg the marketing. version ahead of the Glatopa launch has been one of the bright spots Although Teva is the world’s largest generic drug manufacturer, it for the company. also markets a substantial specialty drug portfolio, focused in multiple sclerosis and respiratory disease. The company has hoped to build the A REPRIEVE MEASURED IN MONTHS specialty portfolio through new launches, like SD-809 for the treat- But how much of a break Teva will get is unclear. Pfizer said in a state- ment of chorea associated with Huntington’s disease and the move- ment that it submitted a corrective and preventive action plan to ment disorder tardive dyskinesia. FDA in May 2016 and is “diligently” implementing the commitments The company announced Feb. 28 that SD-809 was granted a prior- made to FDA. However, the latest warning letter says Pfizer’s actions ity review for tardive dyskinesia, and the application has a Prescription are inadequate and lays out further actions. Drug User Fee Act action date of Aug. 30. But Copaxone makes up The FDA letter cites five manufacturing violations, including the pres- more than half of Teva’s specialty sales; Teva reported $4.22bn in Co- ence of visible particulates in several sterile injectable products, which paxone revenues in 2017 in an $8.67bn specialty segment. the agency said represents “a significant loss of control in your manu- Pfizer acquired the manufacturing facility in McPherson with the ac- facturing process and represents severe risk of harm to patients.” As ex- quisition of the sterile injectables specialist Hospira Inc. in September amples, the letter cites vials of the antibiotic vancomycin hydrochloride 2015 for $17bn. and the non-steroidal anti-inflammatory ketorolac tromethamine. Published online 28 February 2017 scrip.pharmamedtechbi.com 10 March 2017 | Scrip intelligence | 3 SCRIP ASKS

What Will Happen Next In Orphan Drug Pricing? Feb. 28 was Rare Disease Day. To mark the occasion, Scrip asked experts the question: Do you see orphan drug pricing coming under pressure over the next five years?

REPORTING BY Joseph Haas, Sten Stovall, Mandy Jackson, Cathy Kelly, Lucie Ellis, Francesca Bruce, Eleanor Malone and Maureen Kenny.

Having their say: We have to recognize that it’s a continuum, that competitive forces • Companies: Genzyme, Sanofi, Akari Therapeutics, Vertex Pharma- will come into play the larger the population being served, and that ceuticals, MyoKardia, Shire phenomenon is accelerating everywhere. And it will accelerate within • Trade associations: EFPIA/EuropaBio Joint Task Force on Orphan Me- the orphan drug envelope too. And it has nothing to do with orphan dicinal Products and Rare Diseases or not orphan, it has simply to do with what is the target population, • Health technology assessment bodies: UK’s NICE and can it support lower prices? • Datamonitor Healthcare We’re in endless discussions on a regular basis around the world he orphan drugs business is seen as one with high mar- about pricing. The discussion has become more intense and the pres- gins, high entry barriers and limited competitive pressure. sures have become more, but the substance of those conversations T But as the field matures, will those dynamics change? To hasn’t changed over the 20 years we’ve been doing this. mark Rare Disease Day on Feb. 28, Scrip asked experts the ques- [We need] to help people think about orphans not as one bucket… tion: Do you see orphan drug pricing coming under pressure over to really get people refocused on this idea of a continuum and [on the next five years? the fact] that the pricing is really very much about the rarity, and that We received a broad range of answers from an equally broad within the orphan drug there’s a large range, or continuum, of rarity. range of stakeholders – from the grandfather of orphan drug companies, Genzyme Corp., to newcomers such as Akari Thera- ELIAS ZERHOUNI peutics PLC and MyoKardia Inc., from industry groups EFPIA and Global President of R&D, Sanofi EuropaBio to the G-BA, which decides on health insurance cov- The real question is going to be the value that you provide for each erage in Germany, from patient organization alliance EURORDIS [product] and there’s not a one price fits all. to US pharmacy benefits managers Express Scripts and Humana So in orphan diseases what is the rare disease? Look at Gen- Pharmacy Solutions. zyme. It’s a rare disease company... At most, it’s taking care of elev- en thousand, twelve thousand patients. Well, it has six thousand DAVID MEEKER employees so you can see that for every two patients we have an Head of Sanofi Genzyme employee. If you say, ‘I want to cut the price,’ to such an extent that First, all pricing, including orphan you cannot sustain that innovation, you would dry out the well for drug pricing, is under pressure. His- rare diseases. torically orphan drugs have in some It’s very, very hard to maintain the machine behind these patients situations or countries been carved that provides not only the innovation but also the support, the manu- out from a general pricing mandate facturing and so forth. but that is no longer the case. The business model, I think, of where there was an understanding Second, if you are in an orphan that you needed to take the risk to develop drugs for five or six thou- disease serving a population of David sand people, that’s what it takes for that to happen. The problem that Meeker 100,000-200,000, the pricing dy- you have is when it’s used for a very different purpose, when these namic or mechanics of that population are very different than if you’re prices are not applied to very reduced populations. serving a population of 1,000-5,000. And that’s where the debate gets lost a bit, because people don’t recognize that orphan is an arbitrary GUR ROSHWALB, definition and rarity is a continuum. CEO of Akari Therapeutics, a UK-based rare disease specialist Third, I actually feel that pricing in the ultra-rare orphan sense will be Not really. Take PNH [paroxysmal nocturnal hemoglobinuria], for ex- under less pressure because there is an understanding of the impor- ample. Before Alexion Pharmaceuticals Inc.’s drug Soliris (eculizumab) tance of the business model to the willingness of people – investors, came to market, people with PNH would die within five to ten years. companies – to invest in potential treatments or cures. It’s a high price That drug’s appearance gave people with PNH back a normal life because there are so few patients; for any given patient it’s perhaps not span, and these patients during those five to 10 years before its ar- affordable for the patient, but at a systems level that’s a small fraction of rival were not leading a normal life. They were severely anemic and the population and the total amount spent on managing that disease had a lot of medical problems. They are often diagnosed in their 30s is extremely low. With time they’ve come to understand that. What and 40s and so this drug has really changed the path of these people payers are pushing back on is “don’t apply that same basic philosophy and given them another 30 to 40 years of life. That’s worth a signifi- across the full spectrum.” cant sum of money. But we shouldn’t be hiding behind the orphan designation. To me And on the flip side, from the payer point of view, you’re usually your pricing is a function of the value, the rarity of the population not talking about that many patients. These diseases are very rare, you’re addressing, the investments that you made to get to market. so for any given payer you might only have two or three, so that $1

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million line item is just not some- should be entitled to the same quality of treatment as other pa- thing they’re going to fight over. tients. Since 2000, the Regulation has been successful in incentiviz- Also, a lot of medical innovation ing research and development of OMPs. Prior to the regulation, only results from rare orphan disease. eight orphan-like therapies were approved compared to the 130 For example, the immune system currently approved. There seems to be a concern that the Orphan part that we’re targeting to treat Regulation incentives are misused. We believe that the incentives PNH, called the complement are well balanced, with very stringent criteria for orphan designation pathway, the immune system based on distinct orphan conditions. does two things in the body – it There is still enormous unmet medical need in rare diseases. Moving identifies foreign stuff and it kills forward, it is important that the rare disease community build on the Gur Roshwalb it. The complement pathway is success of the European OMP Regulation and work closely together, one of the bridges between identification and the destruction, and including with payers, to continue supporting patients. in auto-immune diseases, complement plays a large role in doing the destruction. TIJANA IGNJATOVIC Innovating the first complement therapy and hopefully bringing Lead analyst for market access at Datamonitor Healthcare others to the market... can have a profound effect on the millions of Getting a successful reimbursement outcome for highly priced people with auto-immune disorders over time. That first drug is expen- orphan drugs will get more difficult in the future. We have already sive, but being able to innovate in that area will make a tremendous seen some cases of this so far, with the recent restriction of reim- difference over time. So, while it’s true that any initial drugs in orphan bursement for Alexion Pharmaceuticals Inc.’s Strensiq (asfotase alfa) areas might be expensive, it pays for very important innovation that in the UK for hypophosphatasia. While the UK may be one of the brings important results further down the line. So I feel there’s a con- most challenging markets, the difficulty Alexion has experienced sensual balance currently between orphan drug innovators, govern- with the reimbursement of Kanuma (sebelipase alfa) in France indi- ment authorities and payers in accepting that that effective ecosystem cates that this is unlikely to be a trend confined to the UK. Kanuma permits rare disease innovation to trickle down over time into broader was also recently rejected by NICE [the National Institute for Health therapeutic areas. and Care Excellence] due to its high price for use on the National Health Service in England and Wales to treat infants, children and STUART ARBUCKLE adults with the rare inherited genetic disorder lysosomal acid lipase Chief Commercial Officer, Vertex Pharmaceuticals Inc., a US- deficiency (LAL-D). NICE was not convinced the high cost of the based specialist company with a focus on cystic fibrosis drug – nearly £500,000 per patient – could be justified by its long- With the recent explosion in understanding of the biology of disease, term treatment benefits in LAL-D patients. we have a new opportunity to fundamentally change the course of The advent of multiple early/conditional market authorization path- human health. Still, developing a transformative treatment for a rare ways is resulting in reimbursement barriers for all drugs approved disease requires a huge investment in terms of both money and through these routes and orphan drugs are more likely to pursue countless hours from talented, dedicated scientists. If we are to fully these pathways. Consequently, they undergo health technology as- sessment (HTA) processes without full, mature datasets, resulting in grasp the opportunity in front of us, society needs pricing policies that uncertainty in the determination of their clinical effectiveness and also incentivize this tremendous effort and ensure companies have the re- cost-effectiveness. Hence, managed entry agreements – which have sources necessary to fund the next set of breakthrough medicines. already been put in place for some orphan drugs – are likely to be used more as a means to address the residual uncertainty. Meanwhile, small EFPIA/EUROPABIO patient populations and treatments being available in specialist cen- EFPIA/EuropaBio Joint Task Force on Orphan Medicinal ters render these drugs highly suitable to participate in such schemes Products and Rare Diseases, a European alliance of over 45 without requiring onerous administrative costs. Some payers (for ex- companies committed to the development of orphan me- ample those in the Netherlands) have had mixed experiences with dicinal products risk-sharing schemes for orphan drugs, but for many this approach will The price of medicines, whether orphan-designated or not, is a topic provide a compromise between ensuring patient access and value for of debate. In Europe, society shares the burden of disease and pub- the healthcare system. lic budgets, including for health, are under unprecedented pressure In Germany, orphan drugs hold an advantage over other drugs in that with spending being carefully scrutinised. by law they have to get an added benefit under the AMNOG early as- Today, it is estimated that the budget impact of orphan medicinal sessment, though it can be reassessed if their expenditure exceeds €50m products (OMPs) is approximately 4-5% of the total pharmaceutical per year. Recently, several groups including the German HTA body IQWiG spending in the largest EU countries that have the best access to rare have called for this rule to be abolished under AMNOG reforms, which disease treatments. This is less than 1% of the overall health expendi- signals another potential risk for the commercial success of orphan drugs ture. As more OMPs are developed, this figure may increase, but esti- in the future and the mates show it should still remain a small portion of health spending need to have a strong in Europe. Also, as most OMPs were developed post-2000, we expect Click here to see what G-BA (Germany), evidence base. generic and biosimilar competition to grow, benefitting budgets. Humana Pharmacy Solutions, Express Scripts, Published online Bay Life Science Advisors and EURORDIS had The European Orphan Medicinal Products Regulation was de- 27 February 2017 to say: http://bit.ly/2lRpGPV veloped on the belief that patients suffering from rare conditions scrip.pharmamedtechbi.com 10 March 2017 | Scrip intelligence | 5 HEADLINE NEWS

Chi-Med Roll Continues With Positive Fruquintinib ALEX SHIMMINGS [email protected]

Chi-Med’s China-focused strategy is pay- lected Phase III trials of the c-Met receptor CEO Christian Hogg said most were first- ing off with positive Phase III top-line re- tyrosine kinase inhibitor are now planned. generation multi-kinase inhibitors with sults for its home-grown VEGF inhibitor These were the two biggest milestones for their attendant off-target toxicities. “They fruquintinib, keeping it on track to for a its pipeline of eight drugs that Chi-Med had don’t concern us one bit.” filing this year. But competition looms. previously penned in for early 2017. He admits competition is more likely “The success of the FRESCO trial is an from Bayer’s Stivarga, but here Hogg he first look at Phase III data for Chi- important milestone not just for CRC believes they have advantages. “Fruquin- Med (Hutchison China MediTech patients and Chi-Med, but also for Chi- tinib is designed to be globally best in T Ltd.)’s new highly selective VEGF nese innovation,” said Chi-Med chairman class. Being where we are with the Phase inhibitor fruquintinib show encouraging ef- Simon To. “We believe this is one of the III data, we are confident it is a better ficacy on both primary and secondary end- first home-grown, China-discovered and drug than Stivarga, both for efficacy and points in third-line colorectal cancer, lead- developed, mainstream innovation in the tolerability.” He also noted that Stivarga ing the way to a filing in China mid-year and field of oncology to succeed in a pivotal costs about $14,000 per month, and the a possible launch in 2018. Phase III registration trial. It shows that market in China would not bear even half Top-line results from Chi-Med’s first piv- China has the resources, capability and that amount. otal trial, FRESCO, in 416 patients with lo- perseverance to emerge as an innovator cally advanced or metastatic colorectal in the global oncology field.” FULLY INTEGRATED cancer in China who have failed at least The company says it is well positioned to Chi-Med is already planning trials of two prior chemotherapies, including fluo- market the product at home, with about fruquintinib in the US to take the product ropyrimidine, oxaliplatin and irinotecan, 2,000 sales reps covering not just the hos- to the rest of the world in due course. Its show a significant improvement in over- pitals in China’s provincial capitals and me- joint development partner, Eli Lilly, cur- all survival compared with placebo when dium-sized cities, but also in the majority of rently only has an interest in China, but given on top of best supportive care (BSC). county-level hospitals. retains an option to obtain global rights. A significant improvement in the key There are no drugs currently approved in Under the companies’ deal, Lilly has two secondary endpoint of progression-free third-line CRC in China, and BSC is the gen- windows of opportunity to exercise this survival was also seen, and no new or un- eral standard of care. Analysts at Deutsche option: a two-month window that started expected safety issues arose. The full results Bank say they believe fruquintinib would with the release of the CRC top-line data to are expected to be reported in the middle be the first tyrosine kinase inhibitor by a gain global rights for $50m up front plus of the year, most likely at ASCO. domestic company to be launched in Chi- development, regulatory and approval The data are another positive step on na targeting this population – they believe milestones, plus royalties, and be responsi- the Chi-Med’s path towards becoming the drug is likely to capture peak sales of ble for 100% of ex-China clinical trial costs; a fully integrated global pharmaceutical approximately CNY1bn ($145m) following or it can wait until up to two months after company, taking its lead from the major a launch in the second half of 2018. the release of data from fruquintinib’s study Japanese companies and staying based in Nonetheless, this market is expected in third-line non-small cell lung cancer (FA- its home market of China. The company is to become much more crowded. The LUCA) in about a year’s time, but here the hoping that recent changes to the Chinese Deutsche Bank analysts say there are five up-front fee would rise to $75m. regulatory environment particularly for in- other innovative small-molecule drugs in Fruquintinib is in two ongoing clinical novative domestic treatments for clear late-stage development in China, while studies in lung cancer, including the piv- unmet medical needs will help propel the Avastin biosimilars are likely to be launched otal Phase III FALUCA study in a planned product more swiftly through the regula- in China in 2H18/1H19. 520 patients in China (topline results ex- tory process than has previously been the “As such, we expect competition in the pected in early 2018), plus an open-label case; it is hoping for approval in early 2018 medium term. For chemical drugs, a Phase Phase II study of it in combination with As- with a launch soon after. Chi-Med says CRC III trial for regorafenib [Stivarga] from Bayer traZeneca PLC’s Iressa (gefitinib) in first-line is the second most common cancer type AG was completed and it is pending for advanced or metastatic non-squamous in China, with about 380,000 new cases manufacturing approval,” they said, adding NSCLC with EGFR activating mutations. per year, according to CA: Cancer Journal that other competitors in Phase III target- A pivotal Phase III registration study is for Clinicians 2016. ing the third-line CRC market include Taiho expected to start during the first half of The FRESCO results follow the recent re- Pharmaceutical Co. Ltd.’s TAS-102, Sino Bio- 2017 in gastric cancer after a successful port of promising Phase II data for another pharmaceutical Ltd.’s anlotinib, Suzhou Zel- Phase I/II dose finding study of fruquin- of its key assets, savolitinib, which is part- gen’s donatinib, and Hengrui Therapeutics tinib in combination with paclitaxel, which nered with AstraZeneca, in papillary renal Inc.’s famitinib. established a combination regimen that cell carcinoma (the second most common Chi-Med, however, is dismissive of its do- was well tolerated. subtype of renal cell carcinoma); patient-se- mestic VEGF rivals. Executive director and Published online 3 March 2017

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CONTINUED FROM COVER with completion of the facility set for 2020. The appointment of immunology ex- of the total €33.8bn generated last year, Zerhouni says the future “is going to pert Yong-Jun Liu, who in March 2016 up sharply from the €1.4bn in 2015 and belong to smart combination therapies was lured away from AstraZeneca PLC €498mn in 2014 that new drugs gener- targeted to very clearly identified popula- where he was head of research at the tions in need”, meaning precision thera- MedImmune biologics business, under- pies with combination medicine. scores the importance of exploring and “The challenges for R&D heads are that developing multi-specific drugs. At Sano- they’ve got to manage the complexity fi, Liu is now working as head of research of biology on the one hand and preci- for global R&D, under Zerhouni. “He has a sion on the other hand. There are very systems view of biology. So do I,” Zerhou- few conditions that you can address with ni said, adding: “the combinatorial game one target.” is what is going to make us successful Sanofi’s aim is to go from mono-target- ... or not successful - but that’s what is ing to multi-targeting, by inventing mol- worth trying.” ecules that can do not just one thing at a time but a number of things. R&D SPENDING TO RISE “You can see it already with MRNAs Zerhouni says the multiple-targeted thera- (Messenger RNA) where you can affect py approach could ultimately help reduce two or three pathways at once with one cost burdens on healthcare systems by re- molecule. The key is that mixing mol- straining drug prices. ecules, having a cocktail of different mol- “Pricing of drugs is going to be helped ecules, is not the same as having a smart, by that combination approach, because multi-targeting molecule. It’s almost like it’s not tenable to have stacked drugs, like a missile with three warheads. Multi-spe- in cancer, for multiple vendors at very high Shutterstock: avarand Shutterstock: cifics. That’s where the long term is go- prices: at some point we have to be smart- ing,” he said. er than that.” ated. Dupilumab - an interleukin-4/IL-13 Duplimumab illustrates that approach. Zerhouni says his R&D strategy’s success inhibitor which has the brand of Dupixent “I tend to look for what I would call in generating a promising portfolio has hap- - is the first biologic to treat the condition the hub molecule strategy, where you pened while keeping spend in a reasonable of atopic dermatitis, having been granted try to pick a molecule when it intersects proportion of overall sales. a priority review by FDA. It is being co-de- multiple disease pathways. The iconic “If you look at our R&D spending relative veloped by Sanofi and Regeneron Phar- example would be dupilumab because to other companies; it is still low at 14% or maceuticals Inc.. it does affect atopic dermatitis, it affects 15%. It’s a spend which has helped, actu- asthma, it affects chronic sinusitis, it’s ally, the overall efficiency of R&D and its BIOLOGICS AND PARTNERING what I mean by saying dupilumab is a productivity.” He stressed that R&D annual spending “What I’ve tried to do is, firstly, to move our pipeline in a single drug. That’s what I’m should not be viewed in isolation. portfolio towards biologics, and not be shy looking for.” “You shouldn’t look at it in one year, you about partnering when we needed to - but Duplimumab is unusual in being a should look at it over a period of years, also not abandoning what I call the funda- monoclonal antibody that has a dual ac- so when you look at that, it’s more in the mental strategy, which is support the fran- tion, acting against both the IL4 receptor 14.5% - 15% actually. … You have an un- chises Sanofi is already in, and then create and the IL13 receptor. der-spending which you’ll see next year is new franchises.” “The reason why I picked that with our going to be overspend. So, you’ve got to Sanofi’s seven therapy areas of focus colleagues at Regeneron is because we bet look at an average.” are diabetes, vaccines and infectious that it would be more effective because But Sanofi’s R&D spending will need to diseases, rare diseases, immunology and both of these receptors act differently on rise going forward, with a target of €6bn inflammation, cardiovascular and me- the same pathway but they are synergis- set for 2020 measured in constant ex- tabolism, cancer, and multiple sclerosis tic in their action in the same pathway. I change rates. “We do see the need to in- and ophthalmology. Late-stage biologic believe it’s going to be the same in many vest more in R&D and we have a pipeline drugs currently comprise some 60% of its other diseases,” Zerhouni said. that is extremely promising, that requires pipeline. Isatuximab, an anti-CD38 monoclonal that investment.” Underscoring Sanofi’s optimism in its antibody currently being trialed for mul- He said Sanofi under its new CEO Brandi- pipeline and anticipation of future de- tiple myeloma, is another example. “It’s one court is now aligning its marketing and the mand for new biologics, Sanofi recently antibody but it has multiple actions and business units globally. entered a joint venture whereby Lonza multiple pathways.” “Before, the organization was more Group Ltd. will build a large-scale mam- Another example of Sanofi’s multi-spe- regionally focused, essentially country- malian cell culture facility for monoclonal cific therapy approach is its GLP-1 GIPR antibody production in Visp, Switzerland, dual-agonist for type II diabetes. CONTINUED ON PAGE 8 scrip.pharmamedtechbi.com 10 March 2017 | Scrip intelligence | 7 HEADLINE NEWS

CONTINUED FROM PAGE 7 based. But when you have 13 launches in three or four years, it does require a Spring Break: Novo’s US Head different view of the business, because you have to grow big products in every Resigns After Rough Winter geography. So, it’s really a business idea Novo Nordisk’s executive VP and head of North American operations, Jakob of having franchises that are vertically Riis, has resigned from the company – a move not completely out of the coherent from top to bottom in the US, blue considering recent rumors of conflict within the diabetes drug Europe, and Japan where most of the developer’s US operations and a lackluster 2016 financial performance for market is.” the whole group. He added that it’s not enough to get an LUCIE ELLIS [email protected] approval for drug. “You have to also strate- gically align it with a market and to getting akob Riis, Novo Nordisk’s head of North market access. So it is necessary to align American operations, has resigned very precisely the research, development, from the company following a tough commercial, medical affairs and market J 2016 and rough winter period for the Danish access for a product along those vertical firm – which reported earnings last month business units.” 2% below analyst’s estimates for 2016. Riis, who has been with the company since 1996, was previously considered ‘Pricing of drugs is going the heir-apparent to recently replaced to be helped by that CEO Lars Rebien Sørensen, who stepped down early from leading the business in combination approach, September last year. Sørensen was instead because it’s not tenable to succeeded by Lars Fruergaard Jørgensen, the company’s former head of corporate have stacked drugs, like in development. Jakob Riis Overlooked for the top job, Riis took cancer, for multiple vendors on the role of North American head last at very high prices’ year, but Scrip reported in December that Riis – who will remain with the com- Novo Nordisk’s US operations were strug- pany for a transition period before taking gling and conflict had risen due to sup- on the role of CEO at Danish emergency posed differing management styles. At services group Falck – will be replaced the time, Scrip was told of strong “cultural by Doug Langa, former senior vice presi- “PEOPLE TALENT” differences” between Novo Nordisk’s dent for market access at Novo Nordisk. Asked for comment on the Britain’s de- European and American management The change in leadership is effective im- cision to leave the EU and US President teams. mediately, the company said, and Langa’s Donald Trump’s stated views on immi- A tough year for the Danish firm, 2016 title will be senior vice president, head of gration, Zerhouni replied: “I can’t com- saw Novo Nordisk twice cut its long-term North America operations and president ment on Brexit or any particular policy growth targets, its then-CEO Sørensen of Novo Nordisk Inc. but I can tell you this: R&D is a global pulled forward his retirement by two years, Relatively fresh blood for Novo Nordisk, enterprise and today R&D talent is at a and the company slashed 1,000 jobs from Langa joined the company from GlaxoS- premium.” its workforce – half of these job losses were mithKline PLC in 2011 as senior director “Any barriers to the exchange of ideas recognized in Denmark and most of the of managed markets. Prior to GSK, Langa in science is not a good thing for hu- rest focused on the US. Novo Nordisk’s spent much of his career at Johnson & manity and so, to me, I can’t predict stock on NYSE has been in steady decline Johnson, where he held various roles with- what Brexit is going to do, what Trump over the last year, falling from a price of in managed markets, sales leadership and Administration policies are going to do $53.15 on March 1, 2016, to $35 pre-market marketing. - but I can tell you with a lot of experi- opening on the same date this year. Langa’s LinkedIn page describes him as ence behind it that restricting scientific Also, during its third-quarter earn- an “industry thought leader driving pharma- exchange restricts progress in biomedi- ings presentation last year, Novo Nordisk ceutical market access innovation.” Based in cal research or any research. highlighted the US as its biggest concern New Jersey and a graduate from New York’s “You don’t know where talent comes for 2017 and the reason for lowering its Fordham Gabelli School of Business – Langa from; it can come from anywhere, anytime growth expectations – resulting in a long- is expected to better bridge the gap be- – and if you restrict it, you lose human po- term growth forecast cut from 15% to 5%. tween Novo Nordisk’s traditional Danish cul- tential.” The US accounts for around half of the in- ture and its failing US business. Published online 1 March 2017 sulin maker’s pharmaceutical sales. Published 1 March 2017

8 | Scrip intelligence | 10 March 2017 © Informa UK Ltd 2017 R&D BITES

Accera Posts Phase III Alzheimer’s Failure Merck & Co’s Shingles Vaccine Clears PhIII Accera Inc.’s failed Phase III clinical trial The first Phase III data presented for Merck & Co. Inc.’s new varicella zoster for AC-1204 is just the latest late-stage vaccine V212 show that it can prevent shingles and reduce pain and other disappointment in a recent string of tri- complications of the virus in recipients of autologous hematopoietic stem al failures in Alzheimer’s disease, but the cell transplants. Another Phase III trial in subjects with malignancies is on- company will move forward with a sec- going. Merck already markets the live attenuated virus vaccine, Zostavax, ond Phase III study based on the drug’s for the prevention of herpes zoster (shingles) in individuals 50 years of age novel mechanism and another new for- and older – currently the only shingles vaccine on the market – but this is mulation. Boulder, Colorado-based Ac- contraindicated in immunocompromised patients. Herpes zoster is caused cera blamed the lack of efficacy observed by the reactivation of the varicella zoster virus, the virus that causes chick- in its first late-stage trial on a new for- enpox (varicella). Merck’s new product, V212, is an inactivated varicella mulation of the drug, because low blood zoster virus vaccine for the prevention of herpes zoster and herpes zoster- plasma levels of AC-1204 were observed related complications in immunocompromised subjects age 18 years and in the placebo-controlled study. But above. This could expand its herpes vaccine franchise in the face of looming while it follows in the fresh footsteps of competition from GlaxoSmithKline PLC’s newcomer Shingrix. Zostavax Eli Lilly & Co., Lundbeck Inc. and Mer- may have enjoyed the market to itself since its launch in 2006, but its sales ck & Co. Inc., which have ended devel- have never been stellar owing to its limited efficacy, particularly in the older opment of three different Alzheimer’s population. Analysts expect Shingrix to hit blockbuster status. The GSK therapies following Phase III crashes product is awaiting approval in the US, EU and Japan for the prevention during the past four months, the private of herpes zoster in adults over 50 years following strong Phase III data in company hopes to forge a different path which vaccine efficacy that was higher than those seen with Zostavax in its two pivotal trials, including in the all-important over-70s population. with AC-1204. CEO Charles Stacey ac- [email protected], 27 Feb 2017 knowledged the difficulty of developing treatments for Alzheimer’s disease (AD), but said in an interview with Scrip that Accera was disappointed that AC-1204 did not achieve the primary endpoint – the company’s attention has turned to avancin), have on average done around a statistically significant improvement Taksta (fusidic acid). Cempra is develop- $7m, $14m and $20m in their first, sec- in cognition at 26 weeks compared with ing the product exclusively in the US for ond and third years on the US market. placebo as measured by the Alzheimer’s acute bacterial skin and skin structure in- [email protected], 28 Feb 2017 Disease Assessment Scale-Cognitive fections (ABSSSI) and is investigating its Subscale (ADAS-Cog) – in the novel use for the long-term oral treatment of drug’s first Phase III test. Accera said the refractory bone and joint infections. The Kite On Course For FDA Filing drug was safe and well tolerated, but the product, which is orally active against company did not provide any detailed Data from the pivotal Phase I/II ZUMA- gram-positive bacteria, such as Staphylo- safety or efficacy results. 1 trial of Kite Pharma Inc.’s CAR-T cell coccus aureus strains including healthcare- [email protected], therapy KTE-C19 in patients with ag- acquired methicillin-resistant S aureus 28 Feb 2017 gressive non-Hodgkin’s Lymphoma will (HA-MRSA) and community-acquired support a rolling BLA submission due MRSA, was non-inferior to linezolid in a shortly and a regulatory filing in Europe Back To The Future: Cempra’s Phase III study. But analysts remain un- later this year. The latest data showed convinced that this is a lucrative market, that responses achieved in patients treat- New Product/Old Antibiotic given the performance of past antibiotic ed with KTE-C19 at the three-month Putting recent disappointments with launches in the US. Cempra is now set mark remained durable at six months. solithromycin to one side, Cempra Inc. to meet with the FDA to see if another The news was greeted with a 16% hike has reported positive Phase III data for pivotal trial is needed. Brian Skorney of in Kite’s share price. “These are positive its second product candidate, an old an- Baird pointed out that recent launches results with the ORR (overall response tibiotic called fusidic acid, which despite in complicated skin and skin structure rate) and CR (complete response) rates being available in Europe for decades has infections and ABSSSI, such as Allergan only degrading slightly from the three- never received a US approval. US FDA re- Inc.’s Dalvance (dalbavancin), Merck & month interim analysis suggesting that jection of Cempra’s solithromycin in De- Co. Inc.’s Sivextro (tedizolid), The Medi- responses are durable,” according to In- cember has pushed the novel antibiotic’s cines Co.’s Orbactiv (oritavancin), and forma’s Biomedtracker analysts. approval back to 2018 at the earliest, so Theravance Biopharma Inc.’s Vibativ (tel- [email protected], 1 March 2017 scrip.pharmamedtechbi.com 10 March 2017 | Scrip intelligence | 9 ROUNDTABLE

Immuno-Oncology 2.0 Roundtable: Emerging Players Eye Crowded Field MANDY JACKSON [email protected]

Scrip spoke with five companies about their places in the crowded IO tion that also don’t add toxicity is really important. That’s another key field in which big pharma and small biotech firms alike are seeking element that we’ve been able to differentiate on as well, and with hav- the best options for harnessing the immune system to fight cancer. ing a 200-patient database of safety, we can actually put the data be- hind what we’re saying. xecutives from Tocagen Inc., CytomX Therapeutics Inc., Trillium ERIC OSTERTAG: Our differentiator is not having any virus; we Therapeutics Inc., Xencor Inc. and Poseida Therapeutics Inc. sat don’t use viruses at all, whereas most of the CAR-T companies use Edown with Scrip to discuss what it takes to get an immuno-on- a virus for transduction of the T cells. I think a virus may be very cology deal done, starting with technology that gives pharma some- good at getting into the tumor, but we do not like it for getting thing it doesn’t have but needs to improve the efficacy and safety of into T cells. Also, it creates very long timelines, it’s very expensive existing immunotherapies. for that use and, maybe most importantly, lentivirus doesn’t get Companies with technology ranging from monoclonal antibodies into early naive T cells. to chimeric antigen receptor T cell (CAR-T) therapies assembled for I think everyone, at least in the CAR-T space, is realizing that the phe- the discussion last month when the biopharma industry descended notype of the cells that you put in is extremely important. You can put on San Francisco’s Union Square for the annual J.P. Morgan Healthcare in an effector-like product, you can get rid of the tumor quickly, but Conference. They took a break from investor meetings and dealmak- then you have relapses, so durability is an issue. Whereas, we have an ing talks to share their thoughts on IO 2.0. almost entirely stem cell phenotype and so we get that initial killing, Scrip’s Mandy Jackson moderated the discussion with Tocagen Vice but then we have engraftment of the stem cells that you can differenti- president of business development and marketing Nicholas Boyle, Cy- ate into tumor effectors, so we get long-term durability and that’s what tomX chief medical officer Rachel Humphrey, Trillium president and we’ve seen in the animal models. CEO Niclas Stiernholm, Xencor president and CEO Bassil Dahiyat, and RACHEL HUMPHREY: CytomX is aiming to be a standalone large Poseida CEO Eric Ostertag. pharmaceutical company. We already have a lot of deals with large SCRIP: Ultimately your customers may very well be pharma part- pharma, because at the end of the day the technology takes vali- ners or acquirers, so what is it that you’re trying to tell them that dated therapies and targets – be it [Bristol-Myers Squibb Co.’s PD-1 you’re doing differently that would add value for them? inhibitor] Opdivo (nivolumab), PD-L1, CTLA-4 – and strengthens or widens the therapeutic window. Or, it takes combinations [where] NICK BOYLE: The way we’ve been building the company since we know have good activity, but cannot be given at all, because in inception is to be prepared to commercialize by ourselves in the all cases sparing the normal tissue is important. United States, so that’s what we focus all of our resources and fi- We’re working with BMS to make a Probody form of [Yervoy (ipilim- nancing towards – achieving that ultimate goal for our lead prod- umab)]. We have our own proprietary PD-L1 agent, other checkpoint uct in the lead indication. inhibitors, both with BMS and as a standalone. We’re working with So when it comes to partnering, and what we hear resonates with AbbVie Inc. in a deal that looks a lot like what you [Boyle] were talk- pharma, they all of course want highly differentiated mechanisms of ing about, which is lots of downstream value for us – combination action – something that could take them beyond the current state of approaches. At this point, it looks like we’re already getting lots of in- IO. At least with respect to the gene therapy space, people are begin- coming excitement, because of the needs right now of managing the ning to recognize what viruses could do in immuno-oncology 2.0 or safety of the agents we already know are toxic and very active, includ- 3.0 or whatever round it would be. ing T cell-redirecting bispecifics that couldn’t be developed before, but We’ve known this for a long time and have been excited about it for in preclinical models have therapeutic windows of 300 or more. a long time, but I think the industry is catching up with what viruses can do. They light the match on tumors; they do turn cold tumors hot NIC STIERNHOLM: I think our spiel is that the immune system – or at least warm – and that’s exactly what our approach does. That is very complex and powerful and we’re just scraping the surface in particular is resonating with the prospect of combination strategies, here with PD-1. We are actually bringing in the innate immune particularly with the deficiencies with the existing checkpoint inhibi- system, because macrophages are not only good phagocytes to tors, because they may not work particularly well in some settings, or chew up the tumor, but they are also quite good at presenting work well at all in other settings, so there’s an intense interest in figur- antigens to T cells. We actually bridge an innate immune system ing out how to make those tumors susceptible to the burgeoning field with the adaptive immune system. We’ve got two arms of the im- of checkpoint inhibitors. mune system going, so we do prime CD8 positive T cells. That’s That’s one area that I think has grabbed a lot of attention from the what pharma likes at this point and I think that that’s where the big pharma guys, but more specifically they think about safety a lot. deals are going to go – to broaden out from just T cells. They don’t want to have additive toxicity on top of the [effects] of BASSIL DAHIYAT: Our experience with what pharma wants is checkpoint inhibitors, so having complementary mechanisms of ac- that they want to be able to rapidly make drug candidates, not

10 | Scrip intelligence | 10 March 2017 © Informa UK Ltd 2017 ROUNDTABLE

prototypes, not surrogates, not research reagents, but rapidly make tor of the US FDA’s Oncology Center of Excellence,] doesn’t want the drug candidates that can give them as many different tools and non-inferiority designs – he has said as much – so under those circum- widgets as they can play with in immuno-oncology. [That may in- stances you can drive value in an enormous market simply by being clude] redirecting against many different tumor targets, because part of the story. you don’t know which ones are really going to be amenable, which ones are going to have the safety, which ones are going to have BOYLE: Are you referring to response rate studies as a pathway actually any efficacy. to approval? They want the tools to rapidly make molecules that can target HUMPHREY: Let’s take the [Phase II IMvigor bladder cancer study the multiple combinations of different antigens you might need for Roche’s PD-L1 inhibitor Tecentriq (atezolizumab)]. That’s a single- to go after, whether one might be on a myeloid cell, one might arm study where they got approval in bladder cancer on the basis be on a T cell, two might be on a T cell, one might be an agonist of showing not a dose effect – this is really clever – but on the basis of an effect where you got better response proportional to the ex- of a T cell, one might be a checkpoint. So this multiplicity, this pression of PD-L1. They could show that if the expression went up, combination [strategy] is the theme in immuno-oncology, and the efficacy went up, and that’s evidenced with a reasonable safety to be able to target that is going to require more and more mol- profile. That was evidence enough for the FDA in a really small study. ecules. We at least can divide that by two, if not three, if we have the ability to robustly make bispecific and multi-specific antibod- DAHIYAT: As an accelerated or as a full approval? ies easily and readily. HUMPHREY: That’s accelerated, because it was a single-arm So our deals look like: we’ll give you [the] rights to use this Fc domain study. But what’s interesting about it is that AstraZeneca PLC had for five of your internal programs. You have to make all the binding a Phase I study with multiple cancer types, [including] a small domains – we’re not going to do any work for you – and you have to bladder cancer setup that must have seen something similar [to pay us for the right to use it. We’ve been doing deals like that for other Tecentriq], but they just filed on Dec. 9. That filing was accepted aspects of what Fc biology can do for about 10 years now and we’re and there’s lot of good reason to believe that the FDA will ap- getting triple the value, both in terms of royalties – we’re going mid-to- prove it. high single digits – and you’re getting multiple hundreds of millions in The difference is that the bladder cancer program for Merck was milestones. We have $45m up front from Amgen Inc. for doing noth- number four or five on their list of approvals, so that was a supplemen- ing for them except handing them our intellectual property for a very tal [biologic license application (BLA)], but this is AstraZeneca’s first. limited set of things, because the demand is so phenomenally high And while they’ve treated enough patients to satisfy the safety criteria, for tools to be able to multi-target antibody molecules in a way that being able to get in with a [PD-1 monotherapy] in a cancer type where nature doesn’t usually let you. others are filing like mad suggests there’s real opportunity there, if you But it’s for drug candidates, not curiosities in the lab, so moving fast can show efficacy with good safety or a sufficient risk-benefit. is critical. I think we’ve seen the lessons that some of the pharmas have DAHIYAT: I don’t think any of the big companies are fooled [by learned by being a couple of years slow in immuno-oncology. Novartis technology that’s not really an immuno-oncology program], like AG is number two in oncology right now in sales, but they will not be Nic was saying. Just because there are more IO companies doesn’t in three years. Who’d have thought that [Keytruda (pembrolizumab) mean there are more deals. I think that for the companies that ac- developer Merck & Co. Inc.] would be a leading oncology company? tually have the real stuff, I would say the partnering environment They got lucky; they hit it with a PD-1 and Novartis was three years late. in IO is the best partnering environment I’ve ever experienced for So, that speed is what everybody wants. People are terrified right now a small company in my career. I think that there’s a lot of noise, but of missing the boat and we’ve got leverage as small companies. pharma companies have whole armies of people designed to say SCRIP: You all have pretty differentiated and different technolo- “no,” so they’re really good at saying “no.” gies. Do you feel like the deal-making environment in this area is SCRIP: Do you find it difficult to even get in the door, because getting easier or harder? I ask that because you’re all working in there’s so much noise? immuno-oncology, which is a hot area, but it also is becoming a DAHIYAT: I wouldn’t say so, because with the amount of hunger crowded space. At least, from my perspective, it seems like the mar- for information by these pharmas, they’re trying to hoover up in- ket’s getting flooded, because all kinds of companies that weren’t formation from everybody, right? really immuno-oncology companies before now say that they are. HUMPHREY: I agree. [They’re] rabid, I would say. STIERNHOLM: That doesn’t fool anyone. DAHIYAT: It doesn’t mean they’re going to buy everything, but I think HUMPHREY: But the billions of dollars in returns continues to the classic case here is what Novartis has done. They’re behind the escalate to such great levels that we’re watching companies cre- 8-ball, so they’ve literally bought or licensed one of every kind of path- ate deals for staggering amounts of money for individual assets. way you can imagine and they’re still buying them. Even if they’re not We’re watching individual companies grab up multiple things getting the best in class, they want one because they figure, “Well, if we over the course of a very short period of time, specifically so they have the best-in-class of this one, the have multiple choices and they can move quickly. third in class of this one, combined And the other thing that I’m observing is that the regulatory hurdles Click here to read the five [we] have the winner.” They’re all do- – I don’t know if others are feeling that way too – but the regulatory companies’ profiles: ing some version of that. hurdles for good immunotherapies, even with some toxicity, is drop- http://bit.ly/2lwcAdU ping. You don’t need the head-to-head trials. [Richard Pazdur, direc- Published online 3 March 2017 scrip.pharmamedtechbi.com 10 March 2017 | Scrip intelligence | 11 HEADLINE NEWS

UK’s Crackdown On Anti-Competitive Deals Continues LUCIE ELLIS [email protected]

The UK’s competition authority is keen Big Generic Players In UK Meanwhile, in December 2016, the au- to expose supposed pay-for-delay deals thority fined Pfizer Inc. and Flynn Pharma • Actavis UK (Teva Company) made by pharmaceutical firms, and is Ltd. nearly £90m for charging excessive • Bristol Laboratories warning drug suppliers to think twice prices for the anti-epilepsy drug phenyt- • Concordia before attempting agreements that slow oin sodium, after that drug was also de- the entry of generic products onto the • Dr. Reddy’s branded – the case is similar to the one UK market. • Lupin being brought against Actavis UK and • Mylan highlights the high penalty Concordia he UK’s Competition and Markets • Sandoz (Novartis Company) and Actavis could be facing. The CMA also Authority (CMA) is once again crack- • Wockhardt has two other investigations ongoing into T ing down on Actavis UK, this time • Zentiva (Sanofi Company) the pharmaceutical sector. alleging that the company signed illegal In a March 3 response to the CMA’s State- agreements with Concordia International during most of this period [January 2013 ment of Objectives, Concordia emphasized Corp. that enabled Actavis’s price hikes for to June 2016], when the cost of the drug that the case raised by the competition au- generic hydrocortisone tablets to be pro- to the NHS rose from £49 to £88 per thority is provisional and no wrongdoing longed in the UK. Over the last year, the pack,” the CMA said. has been confirmed. The company said it CMA has fined Actavis once for its part in an In a separate case, announced in Decem- would cooperate fully with the CMA. “We anti-competitive deal with GlaxoSmithKline ber 2016, the CMA provisionally found that believe that the conduct of Amdipharm PLC and launched two investigations into its Actavis UK had been imposing “excessive” was not in breach of competition law. We conduct in the UK. price rises on its generic version of hydro- will review the CMA’s provisional position In a March 3 statement, the CMA says cortisone. This action was possible because as set out in its Statement of Objections a pay-for-delay agreement between Ac- the product is now off patent and therefore and then intend to respond in detail to it,” tavis and Concordia, which has spanned not subjected to NHS price regulation the Concordia said. several years, has deprived the National same way branded drugs are. The CMA said Health Service of “the significant price falls Actavis had raised the price of hydrocorti- FREE MARKET PRICING that would be expected to result from true sone 10 mg tablets by 12,000% compared In the UK, generic manufacturers and competition.” Concordia was the first po- with the price of the branded version sold suppliers have freedom of pricing, with tential competitor to Actavis UK to obtain by another company before April 2008. The Government only intervening if pricing a marketing authorization for 10mg hydro- amount the NHS was charged for packs of competition fails to keep drug prices low cortisone tablets. the product soared from £0.70 ($0.90) in – such as in he current case against Acta- “We allege these agreements were in- that month to £88 by March 2016. vis UK. This is different to a lot of European tended to keep Actavis UK as the sole sup- Hydrocortisone tablets are used as the countries that use centralized tendering or plier of a drug relied on by thousands of primary replacement therapy for people other grouped mechanisms. patients – and in a position which could whose adrenal glands do not produce The British Generic Manufacturers As- allow it to dictate and prolong high prices,” sufficient amounts of natural steroid hor- sociation has continually lobbied for the Andrew Groves, CMA senior responsible of- mones (adrenal insufficiency), as for exam- UK to retain freedom of pricing in the UK ficer, said in a statement. ple with Addison’s disease. for generic products – arguing against The competition authority has released centralized tendering in primary care. It a Statement of Objections provision- OTHER CASES PENDING also says on its website that it believes a ally finding that both companies broke The CMA has recently been chasing nu- cost increase is needed in the UK “to cre- competition law. The CMA has also sug- merous cases of supposed pay-for-delay ate an economically sustainable market gested that Auden McKenzie Ltd., which deals in the UK between pharmaceutical for manufacturers and to ensure that they was acquired by Actavis in 2015, abused companies and it has already fined Ac- can sustain the investment needed to its dominant position by inducing Amdi- tavis in the past for its involvement in an produce new more complex generics and pharm (now owned by Concordia) to de- anti-competitive agreement with GSK. In more costly biosimilar medicines.” lay its independent entry into the market February 2016, the CMA fined GSK, Gener- The BGMA would not comment on the with a generic hydrocortisone product. ics UK and Actavis a total of £45m for anti- current cases against Actavis, but Warwick The CMA’s statement says that Actavis UK competitive agreements in relation to the Smith, director general of the BGMA, said: “We supplied Concordia with a fixed supply supply of the anti-depressant drug parox- have consistently made very clear that we of its own 10 mg off-brand hydrocorti- etine. The bulk of that fine was charged to would never support any activity which arti- sone at a “very low price” for Concordia GSK, despite the UK big pharma continu- ficially raises the prices of medicines without to resell in the UK. “Actavis UK remained ing to claim it did nothing wrong. GSK has good cause or clear benefit to patients.” the sole supplier of the tablets in the UK since appealed this fine. Published online 3 March 2017

12 | Scrip intelligence | 10 March 2017 © Informa UK Ltd 2017 POLICY & REGULATION BRIEFS

China’s New Curbs On Rep Sales Activities Janssen’s Drug Pricing Report Emphasizes First came a warning, but few expected Value Of Rebates an outright ban to come so soon. Since January, when CCTV, China’s state- Janssen Pharmaceutical Cos.’s report on 2016 price increases shows that run broadcaster, shocked the nation by the company has kept average list price (wholesale acquisition cost) hikes broadcasting scenes of droves of medi- below 10% for the past five years, while the average net price change (WAC minus rebates, discounts and returns) has ranged from 2.5% to 5.2%. The cal sales reps strolling through large Johnson & Johnson unit’s first annual US Transparency Report, released hospitals distributing envelopes stuffed Feb. 27, also includes information about clinical data transparency and with kickback cash to physicians in programs that support access to medicines. J&J CEO Alex Gorsky an- exchange for their drug prescriptions, nounced in a Jan. 24 earnings call that the company would be issuing an industry observers have been anxiously annual report on pricing transparency for its drugs. The report comes as waiting for a clampdown from regu- the industry has continued to face fierce criticism over the high cost of lators on such activity. The last time drugs and sought to portray pricing in the context of other healthcare ex- comparable irregularities in pharma penses. The day after the report was issued several members of Congress companies’ commercial activities came once again introduced bills in the House and Senate to allow Americans to to light, the government handed out import low-cost medicines from Canada. In its report, Janssen emphasizes the largest ever corporate fine in China the value of its discounts and notes that it sets prices below that of its com- of CNY3bn ($436m) to UK-based mul- petitors. The company notes that discounts and rebates to insurers, phar- tinational GlaxoSmithKline PLC. This macy benefit managers and others totaled approximately $11bn in the US, time the government has issued a tough or a discount rate of 35.2%. new rule that effectively bars company [email protected], 1 March 2017 medical sales reps from selling drugs. The new apparent ban has raised ques- tions over whether drug manufacturers should be taking more action to reign (UDCA) in adults with an inadequate agreement may not be suggestive of the in their medical sales reps (MRs), com- response to UDCA, or as monotherapy control exercised by Novartis over its mented Sidley & Austin lawyers Lei Li in adults unable to tolerate UDCA. US co-marketing partners in terms of pric- and Chen Yang. The overall govern- approval by the FDA was secured in May ing, “in reality” the firms have formed ment message, however, seems clear - last year. “Ocaliva’s approval in PBC will a price cartel in both the trade and in- pharmaceutical reps will be subject to likely strengthen its commercial poten- stitutional businesses. “This is clearly more scrutiny, analysts say. tial in NASH by allowing the drug to de- anti-competitive and a clear case of bla- [email protected], 2 March 2017 velop physician familiarity,” Datamoni- tant cartelization,” the whistle-blower tor Healthcare analyst Jack Allen told said in the letter as per a report in the Scrip. Intercept is already testing Ocaliva local media. Novartis has been selling Intercept Boosts NASH in Phase III for NASH in the REGENER- vildagliptin and vildagliptin in com- Commercial Potential ATE study, but there have been concerns bination with metformin hydrochlo- over the speed of patient recruitment ride in India since 2008. The product NICE, the HTA body for England and and the company also recently made is sold under different brand names Wales, has made a final appraisal de- some protocol changes. by its partners Abbott (branded as termination recommending Intercept [email protected], 2 March 2017 Zomelis), USV Ltd. (Jalra) and Emcure Pharmaceuticals Inc.’s FXR agonist Oca- Pharmaceuticals Ltd. (Vysov). Novartis liva (obeticholic acid) for routine use on told Scrip that it is committed to high the National Health Service (NHS) for Novartis Under A Cloud standards of ethical business conduct the treatment of primary biliary cholan- and regulatory compliance in all as- gitis (PBC). However, the company’s key Novartis AG finds itself in a spot in In- pects of its work. “Novartis has received commercial success lays in securing ap- dia after a whistle-blower alleged that no communication from the NPPA or proval for the product in non-alcoholic the Swiss multinational and its licen- the Competition Commission of India steatohepatitis (NASH), a much larger sees for Galvus (vildagliptin) have col- about any complaint against vildaglip- market with no approved therapies. In luded to set prices of the product in tin. Nonetheless, we wish to reiterate December 2016, Ocaliva was condition- the country. The whistle-blower, who that vildagliptin is a patented com- ally approved in the EU for the treatment sent a letter to India’s National Phar- pound and we are in full compliance of primary biliary cholangitis (PBC) in maceutical Pricing Authority (NPPA), with the law,” it said. combination with ursodeoxycholic acid has claimed that while the business [email protected], 1 March 2017 scrip.pharmamedtechbi.com 10 March 2017 | Scrip intelligence | 13 EXPERT VIEW

Hemophilia: How To Please Payers And Secure Market Share Pharma companies are bringing forward innovative products that are set to shake up the hemophilia market – but convincing payers that they have substantial benefits over the current standards of care will be a challenge. Real- world data and early conversations with payers will be key, new research has found.

LUBNA AHMED [email protected]

he hemophilia market is expecting PREFERRED PIPELINE AGENTS slightest additional medical benefit because an influx of new products currently Compared with long-acting recombinant the transparency commission committee T at the later stages of clinical devel- agents, both emicizumab and fitusiran is likely to recognize the burden of the infu- opment, including gene therapies, that will offer significant improvement in dosing sion for toddlers, at least in pediatrics that pile pressure on payers looking to contain frequency for hemophiliacs both with would be acceptable. I think there might costs. To secure market access, it will be and without inhibitors. Emicizumab is an also be a grade on the medical benefit for critical for companies with entirely novel anti-Factor IXa/X bispecific antibody with improved adherence or compliance reasons, hemophilia therapies, as well as those pro- a unique mechanism of action and longer and if not the economic committee is also viding incremental treatment benefits, to half-life of four to five weeks. It is currently likely to most probably recognize the benefit, start conversations with payers as soon as in clinical trials with a treatment protocol and recognize that some kind of risk shar- possible. Care should also be taken over the of weekly up to monthly injections. Data- ing agreement, some kind of patient access design of clinical trials in order to maximize monitor Healthcare forecasts the launch scheme may be acceptable because there is a new product’s attractiveness. of emicizumab in 2018/2019 following the something that is genuinely new.” New research published by Datamonitor submission of Phase III data in hemophilia A Healthcare shows that payers are likely to patients with inhibitors (Haven 1) sometime FORMULATION favor therapies that substantially reduce the in 2017. Roche, in partnership with Chugai Unlike the current therapies for hemophilia, frequency of dosing for prophylaxis, elimi- Pharmaceutical Co. Ltd., also plans to sub- which are administered intravenously, both nate bleeds and have new mechanisms of mit the Phase III data in hemophilia patients emicizumab and fitusiran have a subcutane- action that do not trigger inhibitor develop- without inhibitors in 2018. ous formulation. Subcutaneous delivery has ment, coupled with subcutaneous delivery. Fitusiran, on the other hand, is a short in- been highlighted by payers as a preferred Payers view frequency and mode of terfering RNA antithrombin inhibitor in Phase feature because it is easier to use and allows administration as important as they have II development that can be given to both treatment to be administered by patients at the potential to improve patients’ treat- hemophilia A or B patients, with and without home, thereby enabling improved patient ment adherence, result in better health inhibitors. Also, in line with payers’ preference, adherence and thus offering the prospect of outcomes and reduce overall treatment fitusiran requires infrequent dosing and may better health outcomes and reduced costs. costs. While the goal of prophylaxis may be administered monthly. A US payer cited in the report said: “I think be to prevent bleeds, this is not viewed as According to one French payer, reducing emicizumab is an exciting product because cost-effective at the moment, leading to treatment frequency to once a month or it is probably the first foray into treating he- suboptimal dosing regimens and under- even less could improve treatment adher- mophilia that is not a factor replacement, it treatment of patients. ence significantly, and result in enhanced actually helps work downstream in the clot- “Payers are looking to contract for pre- quality of life and learning abilities for chil- ting cascade... It is exciting because maybe ferred products in the future, so differenti- dren, thus attracting superior reimburse- you are going to have something there that ating the products (with features like new ment prospects: you can give relatively infrequently, and re- formulation, longer half-life), conducting “I would be much more optimistic about ally prevent bleeding.” the proper trials with the proper arms and long-acting technologies, not just extending endpoints (for example, including patient- the half-life a bit, because today for example INHIBITOR SEGMENT reported outcomes as well), are all things Elocta [Sobi/Biogen’s recombinant factor In addition, these products address the needs manufacturers can do to optimize their VIII Fc fusion protein to be administered ev- of an underserved patient segment. Both products’ commercial potential,” noted Dat- ery 3-5 days as a prophylactic injection] got agents could offer new options to severe amonitor Healthcare analyst, Maha Elsayed, ASMR V [an assessment of no clinical added hemophiliacs with inhibitors, where there is author of a new report, Hemophilia Pricing, value over existing therapies], and I was not a gap in the market. While only one third of Reimbursement and Access. surprised at all, I was very much anticipat- hemophiliacs develop inhibitors against clot- The report highlights that payers have ing this kind of outcome. Now, if you have ting Factor VIII or IX therapies, these patients named Roche’s emicizumab and Alnylam a technology that would be once a month are the most difficult and expensive to treat, Pharmaceuticals Inc./Sanofi’s fitusiran as the instead of every other day, then I would sup- and have limited therapy options. most anticipated pipeline agents for a variety pose that the manufacturer would [be re- “Obviously, the inhibitor patients are of reasons. warded with an assessment of] at least the very expensive, they often have to be

14 | Scrip intelligence | 10 March 2017 © Informa UK Ltd 2017 EXPERT VIEW

treated with things like Novo Nordisk’s COMMERCIAL POTENTIAL Phase II development, including BioMa- bypassing agent NovoSeven and other Elsayed predicts that emicizumab will rin Pharmaceutical Inc.’s BMN-270, Spark quantities of factors, and they can some- take a large chunk of market share in he- Therapeutics Inc.’s SPK-8011 and uniQure times spend in excess of a million dollars mophilia A patients with or without in- NV’s AMT-060. per patient per year,” said one US payer. hibitors. However, those already in this Payers, however, are not yet keen on this market can do various things to optimize form of therapy for two reasons: firstly, cur- PAYERS’ DATA DEMANDS their commercial potential and help offset rent healthcare systems are organized in To maximize reimbursement success, the emerging competitive threat. For ex- such a way that they do not support one-off pharmaceutical companies should look ample, manufacturers can develop phar- payments, something gene therapy would to demonstrate their products’ value by macokinetic services – along the lines of entail. A single one-off treatment necessi- establishing benefit in relation to stan- PKFit, which Baxalta/Shire provides for tates a different pricing model from that in dard of care treatment. “For new pipeline Advate – to individualize therapy and limit place for long-term, ongoing therapies. In products, they need to design their trials excessive factor use. While payers are not addition, payers are not likely to be willing to better, have the right comparator in an willing to pay significantly more for these pay a high figure without evidence of long- adequately powered trial,” Elsayed said. value-added services, they can help boost term efficacy. At the moment, not all trials compare market share. Another value-added ser- Elsayed says that companies need to dis- the pipeline product with standard care vice that companies can leverage to stay cuss with payers how to approach these pay- of therapy. Rather, the majority compare on top of competition is offering special- ments and the shape of the new financial mode of therapy such as on-demand (the ist healthcare delivery services to patients arrangements so that they can be prepared clotting factor is given when there is a treated at home, which would be especial- to contribute the data required. Potential bleed) versus prophylaxis. ly valuable in some countries where avail- options discussed by payers included annu- In the report, payers also mention that ability of support services is limited. ity-based payments linked to an outcome- studies are under scrutiny and should based agreement, meaning payment will be meet certain requirements if developers made as long as the treatment is effective. want their drug to gain an added ben- They also mentioned an alternative, partial efit or price advantage. They stressed the upfront payment that is based on duration of need for head-to-head comparative tri- response provided in trials, with the remain- als to prove whether a product provides ing paid on an annual basis. any real benefit or not. A minimum of a Legal changes will also be required within one-year trial is preferred, with the most health insurance frameworks. Considering important endpoint being annual bleed- how rare the disease is and the high upfront ing rate (ABR). A detailed analysis of se- Shidlovski Shutterstock: costs, there is potential for difficulties to arise vere bleeding rates or bleeds leading to around which insurance funds pay for and hospitalization are also desired by payers In countries like France, Roche for example which one benefits financially from the gene and can support a product’s value prop- has the option of seeking a Temporary Au- therapy. As a result, gene therapy developers osition. Further analysis of the impact on thorization for Use scheme (ATU) for emici- will need to communicate with stakehold- healthcare resource use can also support zumab, giving it the opportunity to provide ers in healthcare systems to move along the reimbursement submissions or price ne- patients with the drug earlier. It will be fund- process of introducing new legal and finan- gotiations. ed and until it receives market authorization, cial frameworks that will make funding gene For example, one Spanish payer said: “I Roche can collect real world data to support therapies possible. Companies will also need to liaise with think that the most important endpoint is pricing and reimbursement negotiations. regulators, the EMA and various HTA bodies a highly clinical relevant endpoint, for ex- about clinical trials and how they should be ample, the number of bleeds or bleeding, GENE THERAPIES designed and the comparator arms to include. or reduction in number of bleeds over time Gene therapy is pegged to have the po- Financial, regulatory and legal barriers are or reduction in number of joint bleeds over tential to transform the treatment of he- not the only hurdles developers will need time. We prefer a clinical endpoint; a clini- mophilia patients with its approach of to think about: there are also trust barriers cally relevant parameter.” correcting and replacing a defective gene, that will require attention, particularly when Meanwhile, a payer from Germany said: potentially once and for all. Nevertheless, it comes to patients and patient advocacy “Not for the G-BA, but during the pricing gene therapy developers have hurdles to groups. negotiation the health economic end- overcome, funding to secure and physi- Analysis from Datamonitor Healthcare points are appreciated. Let us say eco- cians to convince before they gain market Published online 3 March 2017 nomic endpoints would be appreciated, access. Pharma companies will need to we do not need health economic models engage with various stakeholders within in the long run or whatever, but any evi- different healthcare systems to make this View Table Summarising Pipeline Product dence that can show us that we can save transition smooth as possible. Features Desired By Payers In Different direct costs compared to older interven- There are various gene therapies in the Markets here: http://bit.ly/2lSSfeY tions would be beneficial.” pipeline, with the majority in Phase I/II or scrip.pharmamedtechbi.com 10 March 2017 | Scrip intelligence | 15 HEADLINE NEWS

Roche’s APHINITY Trial Boosts Outlook On Its Oncology Business STEN STOVALL [email protected]

Roche released positive headlines from That’s because observers are closely HER2-postive breast cancer setting. “Roche its APHINITY trial examining use of Her- watching Roche’s succession plans for its intends to file on a global basis, which we ceptin and Perjeta together in the adju- HER2 franchise, which has already revo- think is encouraging, because this indicates vant treatment of breast cancer, offering lutionized the treatment of breast can- it believes the data will be strong enough to promise that its aging oncology franchise cer. Of particular interest are new drugs secure adoption on a wide basis,” they said. can be protected. Perjeta and Kadcyla (ado-trastuzumab The significance of the trial reflects the emtansine), the antibody-drug conjugate fact that treating breast cancer effectively version of Herceptin. Roche hopes thera- and early, before it has spread, may im- pies like those will replace revenues lost prove the chance of preventing the dis- when its three top-selling drugs Herceptin, ease from returning and potentially reach- Rituxan/MabThera (rituximab) and Avastin ing an incurable stage. (bevacizumab) – which account for some Herceptin is Roche’s second-biggest $20bn in yearly sales – begin to lose pat- earner after Avastin. Some 70% of Roche’s ent protection in the next three years. $6.8bn Herceptin sales came last year Perjeta has already been approved in the from patients who might benefit from US in combination with Herceptin in meta- the combination being tested in the APH- static disease, and received accelerated ap- INITY trial. Shutterstock: designer491 Shutterstock: proval in the pre-surgical, or neoadjuvant, huge sigh of relief accompanied setting, where it has been shown to reduce ‘These results serve Roche’s announcement Mar. 2 that the size of tumors. Athe keenly-awaited Phase III APHIN- APHINITY is evaluating Perjeta’s ability as confirmation for the ITY trial showed that Perjeta (pertuzumab), to stop the recurrence of the disease for conditional approval combined with Herceptin (trastuzumab) women who have undergone surgery, or and chemotherapy, extended disease- “adjuvant” treatment, which if successful and will assure label- free survival in patients with HER2-positive would greatly boost the number of pa- expansion approval’ early breast cancer when compared with tients eligible for the combination of HER2- Herceptin and chemo alone, and that no blocking agents. new safety signals were seen. “These APHINITY results serve as confir- APHINITY’s aim was to show that adding mation for the conditional approval and But while positive for Roche, Datamonitor Perjeta would significantly improve inva- will also assure the label-expansion ap- Healthcare analyst Zachary McLellan says sive disease-free survival rates in women proval of Perjeta for adjuvant treatment. the APHINITY trial’s results “are a significant with early HER2-positive breast cancer. By This label expansion will help Roche in- blow” to Puma Biotechnology Inc. and its meeting the primary endpoint, Roche’s crease its revenues even as it faces com- pan-HER inhibitor, neratinib. Puma is trying combo has boosted prospects the world’s petition from Herceptin biosimilars,” said to position its lead asset for the extended biggest maker of cancer drugs can off-set BioMedTracker analyst David Dahan. adjuvant setting after treatment with Her- biosimilar threats to its oncology business ceptin in breast cancer patients. with new therapies. Some 40% of group REGULATORY APPROACH “Neratinib has not been studied in revenues are set to face biosimilar compe- Roche said it would now discuss the APH- patients that received both Perjeta and tition over the next five years. INITY results with the FDA and European Herceptin treatment and will not be in- Medicines Agency (EMA) as well as HTA au- dicated for use in these patients. So, if ap- APHINITY DETAILS thorities for potential approval of the drug proved, neratinib will likely see little to no But analysts and investors must await full mixture for treating people with HER2-posi- uptake in its targeted indication,” McLel- details from APHINITY. Analysts think that tive early breast cancer. lan told Scrip. will occur at this June’s American Society “We cannot speculate on the timing of BioMedTracker’s Dahan agreed, adding: of Clinical Oncology (ASCO) meeting in potential regulatory decisions. We hope to “detailed results will be key - and it will be Chicago, Illinois. “Without full details of the bring this treatment option to patients as interesting to see how Perjeta performed data, some degree of hand-wringing will soon as possible,” a Roche spokesperson said. in patients with hormone-receptor posi- likely continue, in terms of just how big the Analysts at Berenberg took heart at tive disease, a subgroup which did very clinical benefit is likely to be,” Bernstein ana- the regulatory approach Roche indicated well on neratinib.” lyst Richard Wagner said in a reaction note. it would use for the combo in the early Published online 2 March 2017

16 | Scrip intelligence | 10 March 2017 © Informa UK Ltd 2017 HEADLINE NEWS

Juno Ends JCAR015 Development In ALL MANDY JACKSON [email protected]

Juno and partner Celgene closed the ROCKET study for JCAR015, therapy field. We remain committed to developing better treat- which has been on clinical hold since November, and ended de- ments for patients battling ALL and believe an approach using velopment in ALL in favor of its new and improved CD19-target- our defined cell technology is the best platform to pursue. We ing CAR-T therapies. intend to begin a trial with a defined cell product candidate in adult ALL next year.” uno Therapeutics Inc. has ended development of its CD19- Although the hold put on ROCKET in July was lifted within a mat- targeting chimeric antigen receptor T-cell (CAR-T) therapy ter of days, the FDA stopped the trial again in November based on JJCAR015 for the treatment of acute lymphoblastic leukemia an unexpectedly high incidence of severe neurotoxicity, including (ALL) due to safety concerns, answering with certainty the ques- five deaths from cerebral edema among the patients treated with tion of whether the company could catch up to its competitors, JCAR015. The study has remained on hold while Juno conducted which will be seeking approvals for their CAR-T therapies any an investigation. day now. “Through the investigation Juno identified multiple factors that Juno said on March 1 in its fourth quarter and year-end 2016 may have contributed to this increased risk, including patient- earnings report that the company and its partner Celgene Corp. specific factors, the conditioning chemotherapy patients received, ended the pivotal ROCKET clinical trial that had been placed on and factors related to the product. Although Juno believes there clinical hold multiple times due to severe neurological side effects are protocol modifications and process improvements that could and patient deaths. The company will focus its efforts in ALL on enable Juno to proceed with JCAR015 in clinical testing in adult its defined cell technology instead, including the CD19-targeting [relapsed or refractory (r/r)] ALL, Juno would first need to establish JCAR017, which it has been promoting as better and safer than preliminary safety and dose in a Phase I trial,” the company said in JCAR015 since the first ROCKET clinical hold. its earnings report. Juno’s stock price fell 7.9% after the stock market closed to $23.30 “As a result of the timing delay that would entail and Juno’s be- per share based on the JCAR015 update, keeping the stock toward lief that it has other product candidates in its pipeline that are the low end of its 52-week range of $17.52 to $49.72. likely to provide improved efficacy and tolerability, Juno, in col- JCAR017 will move into a pivotal Phase II clinical trial in non- laboration with partner Celgene, has made a strategic decision Hodgkin lymphoma (NHL) at some point in 2017, keeping Juno a to cease development of JCAR015 at this time and to redirect as- year or more behind Kite Pharma Inc. and Novartis AG, which are sociated resources to the development of a defined cell product expected to submit their CD19-targeting CAR-T therapies for US candidate in the adult r/r ALL setting,” Juno reported. FDA approval during the first quarter of this year. Kite is pursuing its first approval for axicabtagene ciloleucel PATENT DISPUTES OFFER UPSIDE (KTE-C19) in the treatment of aggressive relapsed or refractory Juno did remind investors about some upside in its earnings report, NHL, including diffuse large B-cell lymphoma (DLBCL), primary however, related to Kite’s CAR-T development programs. The com- mediastinal B-cell lymphoma (PMBCL) and transformed follicular panies are engaged in two separate patent disputes, including an lymphoma (TFL), and reported durable response rates through inter partes review that Kite sought with the US Patent and Trade- six months of treatment from its ZUMA-1 study on Feb. 28. The mark Office (USPTO) Patent Trial and Appeal Board (PTAB) in August first potential indication for Novartis’s CTL019 will be relapsed or 2015 related to a patent for CAR-T technology used in the treatment refractory pediatric ALL. of B cell and other malignancies, which Juno licensed from the Sloan- Juno insisted in its 2017 financial update that JCAR017 will keep Kettering Institute for Cancer Research, an affiliate Memorial Sloan the company in a competitive position in the CAR-T field, posi- Kettering Cancer Center. The PTAB upheld all of the patent’s claims, tioning its next-generation CD19-targeting product candidate as but Kite has appealed the decision to the US Court of Appeals for the a potential best-in-class product. The overall response rate (ORR) Federal Circuit. for NHL patients treated with JCAR017 in the Phase I TRANSCEND Meanwhile, Juno has filed a lawsuit against Kite claiming axi- clinical trial was 80% in data reported in December during the cabtagene ciloleucel infringes the patent upheld by the PTAB, American Society of Hematology (ASH) annual meeting with a 60% which covers a CD19-targeting CAR-T construct that uses a cer- complete response (CR) rate. tain CD28 co-stimulatory domain. If the court issues a declaratory In Kite’s Phase II ZUMA-1 study, at six months the ORR was 82% judgment in Juno’s favor or if the two companies reach a settle- and the CR was 41%. ment, Kite could be on the hook for licensing fees, royalties or “We continue to experience encouraging signs of clinical ben- other payments. efit in our trial addressing NHL,” Juno President and CEO Hans A lawsuit settled in 2015 related to a separate patent resulted in Bishop said in the company’s March 1 statement, “but we also Novartis agreeing to pay Juno $12.25m plus future milestone fees recognize the unfortunate and unexpected toxicity we saw in and royalties. The settlement ended a dispute between Novartis’s our trial addressing ALL with JCAR015. We have decided not to partner the University of Pennsylvania and Juno’s partner St. Jude move forward with the ROCKET trial or JCAR015 at this time, even Children’s Research Hospital. though it generated important learnings for us and the immuno- Published online 1 March 2017 scrip.pharmamedtechbi.com 10 March 2017 | Scrip intelligence | 17 R&D STRATEGY

WHO’s List Of Pathogen Threats To Rouse Developers The World Health Organisation has released a list of 12 bacteria it says pose the greatest threat to human health as a way of urging governments and the drug development industry to incentivize and launch an R&D response against the increasing global issue of antibiotic resistance. LUCIE ELLIS [email protected]

he World Health Organisation has highlighted 12 families of bacteria, the majority of which have become resistant to T available antibiotic treatments, on a newly established watch list of critical threats – similar concerns as those raised by the US Cen- ters for Disease Control and Prevention (CDC) in a 2013 report on the top 18 drug-resistant threats. The WHO’s list highlights in particular the threat of gram-negative bacteria that are resistant to multiple antibiotics. “This list is a new tool to ensure R&D responds to urgent public health needs,” Dr Marie-Paule Kieny, the WHO’s assistant director-general for health systems and in- novation, said in statement. “Antibiotic resistance is growing and we are fast running out of treatment options. If we leave it to market forces alone, the new antibiotics we most urgently need are not going to be developed in time,” she added. The WHO’s list of bacteria families – developed in collaboration with the division of infectious diseases at the University of Tübingen, Ger- Kateryna Kon Shutterstock: many – is split into three priority categories: critical, high and medium. pathogens highlighted on its watch list. The WHO is also consid- PRIORITY 1: CRITICAL ering a global stewardship framework for monitoring and guiding • Acinetobacter baumannii, carbapenem-resistant the best use of antibiotics worldwide, looking for at the develop- • Pseudomonas aeruginosa, carbapenem-resistant ment of new drugs and how to repurpose available anti-infec- • Enterobacteriaceae, carbapenem-resistant, ESBL-producing tives. Futhermore, the organization has an ongoing partnership with the non-profit group Drugs for Neglected Diseases Initiative PRIORITY 2: HIGH (DNDI), focused on stimulating new R&D methods for antibiotics. • Enterococcus faecium, vancomycin-resistant “The purpose of this list was to define more precisely the bugs we • Staphylococcus aureus, methicillin-resistant, vancomycin-interme- need antibiotics for most, to direct research efforts to the areas with diate and resistant the most need,” Hill said. She compared the list to some of the WHO’s • Helicobacter pylori, clarithromycin-resistant previous projects, such as the 2013 Priority Medicines for Europe and • Campylobacter spp., fluoroquinolone-resistant the World report and the R&D Blueprint for Action to Prevent Epidem- • Salmonellae, fluoroquinolone-resistant ics that was released in May last year. • Neisseria gonorrhoeae, cephalosporin-resistant, fluoroquinolone- The list has received more than 124,000 downloads since its resistant release on the WHO’s website on Monday Feb. 27. Hill noted that one query raised about the list so far is the fact tuberculosis was PRIORITY 3: MEDIUM not included as a threat. She clarified that while new drugs for • Streptococcus pneumoniae, penicillin-non-susceptible TB is a major priority for the WHO, it is an initiative that has been • Haemophilus influenzae, ampicillin-resistant defined for some years. “The idea of this list was to go beyond the • Shigella spp., fluoroquinolone-resistant pathogens where we already have priority measures in place,” Criteria for selecting the pathogens on this list included how she added. “We know TB, malaria and HIV, for example, need new many treatment options remain and whether new antibiotics to drugs – these have been R&D priorities for some time.” treat them are already in the pipeline; as well as measures like how deadly the infections caused are and whether hospitals stays are re- INDUSTRY INCENTIVES quired for those infected. Hill highlighted that current antibiotic developers or those look- Dr Sue Hill, director of the department of essential medicines and ing to expand into antibiotic research should not only focus on health products at the WHO, told Scrip, “Even though there has been pathogens highlighted as critical risks. “Drugs targeting the a lot of investment in the last couple of years from both private and pathogens in the medium threat category might be easier or public funding aimed at stimulating R&D for antibiotics, what we still cheaper to developer. One of the reasons the critical group has see is a relatively limited number of products in the pipeline.” that heading is because we have more problems with resistance Hill noted that one of the WHO’s next steps this year is to carry there and see fewer product coming through the pipeline.” Hill out a thorough pipeline analysis for treatments targeting the realizes that the economic setup for developers of new anti-

18 | Scrip intelligence | 10 March 2017 © Informa UK Ltd 2017 R&D STRATEGY

biotics is still unfit for purpose. “It is clear the standard market Phase I study is slated for completion by June this year. Antibiotic models are not working and are inappropriate,” she said, “the last treatments against Pseudomonas aeruginosa are more advanced thing we want are new antibiotics developed and sold to mil- than A. baumannii. Biomedtracker has two Phase II programs lions of people. We want a new drug developed and locked up listed: MEDI3902 from AstraZeneca PLC and panobacumab from for future use.” Aridis Pharmaceuticals LLC. AstraZeneca’s drug has been grant- Hill noted that this requires different thinking around incentives be- ed Fast Track status in the US and topline data from the Phase II cause companies are asked to invest in developing products but at EVADE trial in mechanically ventilated patients for the prevention the same time told not to sell them. “We have to think about whether of nosocomial pneumonia caused by pseudomonas aeruginosa buying out patents is an option, offering prizes – for example, like the are expected in 2018. FDA’s priority review voucher system. We are having these discussions Targeting Enterobacteriaceae, Achaogen Inc., in partnership with now to see what will be the appropriate mechanisms for incentivizing Ionis Pharmaceuticals Inc., has three Phase III trials ongoing for antibi- companies,” she said. otic candidate plazomicin. The drug is being tested as a treatment for As well as industry’s response to the list, Hill hopes to spur academic urinary tract infections, septicemia and hospital acquired pneumonia. groups and basic science researchers to act on the call to arms against antimicrobial resistance. COMPARISON TO CDC ANALYSIS In 2013 the CDC published a report outlining the top 18 drug-resis- WHAT’S IN THE PIPELINE? tant threats, also categorized by level of concern: urgent, serious and Pipeline activity for the three pathogens highlighted by the WHO as concerning. critical threats – Acinetobacter baumannii, Pseudomonas aeruginosa The pathogens at the top of both these lists remain similar four and Enterobacteriaceae– is limited, concentrated mainly in the early- years apart, highlighting the slow progress in uptake of antibiotic re- stages of development. search programs. The WHO’s number one concern, resistant Acineto- According to data held by Informa Pharma Intelligence’s bacter baumannii, also topped the CDC’s serious threats list in 2013. Biomedtracker, there are only three compounds in development However, Neisseria gonorrhoeae was labelled an urgent threat in the targeting Acinetobacter baumannii gram-negative bacteria, of US in 2013, but this pathogen has only been categorized as a high these only one has entered the clinic. Entasis Therapeutics has priority in 2017 by the WHO. a Phase I program (active in Australia) for EXT2541, a broad and Drug resistant Pseudomonas aeruginosa, a critical threat on the potent inhibitor of class A, C, and D beta-lactamases. The compa- WHO’s list, was also considered a serious threat by the CDC four ny is developing the combination of sulbactam and ETX2514 for years earlier. the treatment of severe Acinetobacter baumannii infections. The Published online 1 March 2017

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Totalling $320m, this was the largest private financing in the life sciences ever in Europe and second largest globally in the sector.

The oversubscribed round included some of the most highly regarded institutions in the health care sector and provided the company with financial security to advance its ImmTAC Winner: Immunocore’s $320m series A financing technology platform and other initiatives.

“This award is a tribute to the hard work and commitment of the whole team behind the $320 million Series A financing round and all of Immunocore’s staff, board and investors. This private capital has enabled Immunocore to continue to work towards bringing our technology to patients.” Scrip Awards Pharma intelligence | informa Eliot Forster, Chief Executive Officer of Immunocore

scrip.pharmamedtechbi.com 10 March 2017 | Scrip intelligence | 19 BUSINESS BULLETIN

New Anti-CMV Therapies Post-Transplant Astellas Builds Vaccine Portfolio Infections caused by cytomegalovirus, Astellas Pharma Inc. is paying $10m upfront to acquire exclusive world- particularly those that erupt during im- wide rights to develop and commercialize a novel pneumococcal disease munosuppression, have been a particular vaccine developed by Affinivax Inc. using the US venture’s proprietary bugbear of transplant patients, but a new Multiple Antigen Presenting System (MAPS) technology. The candidate, generation of anti-CMV agents are near- used to prevent infections caused by the Streptococcus pneumoniae bacte- ing the market, with Merck & Co. Inc.’s rium including pneumonia, meningitis, and sepsis, is Affinivax’s lead pipe- letermovir forging ahead in the latter line project and is still at the preclinical stage, but has shown promising stages of the race to market.Letermovir signs of activity. As part of the new agreement, Astellas will lead and fund is described as a first-in-class viral termi- in full a planned global clinical development program, with Affinivax eli- nase complex inhibitor that unlike mar- gible for further undisclosed milestone payments related to development, keted CMV therapies is not a nucleoside approvals in targeted indications, and commercial sales, plus tiered royal- derivative but a quinazoline, and has no ties. Astellas said there would be no financial impact from the deal on its activity against other viruses. Worldwide existing guidance for the fiscal year ending March 31. The deal builds on rights to the product were bought by existing links forged in September 2015 between Affinivax and Astellas’s Merck in 2012 with an upfront payment vaccines R&D partner ClearPath Development Company LLC to research of $143m and $433m in development, prophylactic MAPS vaccines for the prevention of bacterial nosocomial in- regulatory and commercial milestones fections. ClearPath, with support from Astellas, set up a dedicated venture, from the Bayer AG spinout and Wup- Nosocomial Vaccine Corp., in that year to develop products in this area. pertal, Germany-based company, Ai- ClearPath and its parent RRD International have been helping Astellas Curis GMBH & Co. KG. Merck intends identify and develop vaccine candidates, which led to the Japanese firm to submit letermovir for approval in the acquiring global rights in 2013 to Mymetics Corp.’s preclinical respiratory post-transplant setting in the US and EU syncytical virus (RSV) vaccine. This product is being developed through during 2017, seemingly putting the com- RSV Corp, another company formed with ClearPath’s support and an As- pany ahead of a small group of potential tellas minority investment in the same year. new anti-CMV agents in late-stage devel- [email protected], 28 Feb 2017 opment that include small molecules, vaccines and cell-based approaches. Fol- lowing a brief announcement on Oct. 19, 2016 that the results of a Phase III study a takeover offer from Mylan NV in 2015. of letermovir to prevent CMV infection It has been pushing for a sale of Perrigo’s in post-bone marrow transplant patients Tysabri stake and its prescription generic Sanofi/Lonza’s JV: Flexible were positive, Merck released further specialty topicals business to help turn Biologics Manufacturing top-line data from the study on Feb. 26, around the firm’s plummeting share 2017, indicating that significantly fewer price. However, while analysts are broadly Construction of a large-scale mamma- patients with undetectable plasma CMV positive about the Tysabri deal, they are lian cell culture facility for monoclonal DNA at the start of treatment developed not convinced Perrigo is solving its prob- antibody production will start in Visp, clinically significant CMV infection in lems effectively. “Five new board mem- Switzerland, this year under terms of the 24 weeks post-transplant, compared bers have recently joined, Tysabri has a joint venture between Sanofi and with placebo-treated patients. been sold, and management has found Lonza Group Ltd. aimed at giving the [email protected], 2 March 2017 $130M in synergies,” wrote Jefferies’ Da- duo commercial flexibility and scalabil- vid Steinberg in a research note dated ity in response to demand for Sanofi’s Feb.28. The potential sale of the prescrip- portfolio of late-stage biologic drugs, Perrigo ‘Unlocks Value’ tion business is still an unknown, but it’s which currently comprise some 60% Perrigo Co. PLC is selling its royalty clear Perrigo’s management is working of its pipeline. The French drug maker stream in multiple sclerosis drug Tysabri hard to create more value. “However, has and Swiss contract development and (natalizumab) to Royalty Pharma for anything actually changed except reduc- manufacturing group said Feb. 27 they up to $2.85bn, following pressure from ing leverage and shrinking the earnings were setting up their first ever JV, un- hedge fund Starboard. The deal com- base? It’s early but we’d say not really. The der which Lonza will design, construct, prises $2.2bn in cash at closing and up to hope is that management can improve start up and operate a state-of-the-art $650m in potential milestone payments. margins at BCH (branded consumer large-scale mammalian cell culture fa- Starboard has highlighted the fact that healthcare) and a floor on generic pricing cility. The two will split the €270m ini- Perrigo’s share value has dropped since can be reached.” tial cost equally. the firm convinced shareholders to reject [email protected], 28 Feb 2017 [email protected], 27 Feb 2017

20 | Scrip intelligence | 10 March 2017 © Informa UK Ltd 2017 EXCLUSIVE INTERVIEW

Shire’s Wellhoefer On Genetic Disease R&D And Expanding Access To Medicines MANDY JACKSON [email protected]

Scrip spoke with Shire’s Head of Genetic Diseases, Medical Af- begins with nonspecific gastrointestinal and pain issues that don’t fairs, Hartmann Wellhoefer about upcoming milestones in the immediately indicate the lysosomal disorder, but a diagnosis often company’s R&D pipeline and improving access to medicines for isn’t established until Fabry patients have progressed so far that rare diseases after the Baxalta merger. they’re on dialysis due to kidney failure. “Uncertainty about diagnosis is a huge burden for families,” Well- hire PLC vice president Hartmann hoefer said. Wellhoefer, head of genetic dis- The earlier a patient with Hunter syndrome is treated, however, Seases, medical affairs, recently the more likely that bone structure can be preserved and joint stiff- spoke with Scrip about the company’s ness can be reduced, potentially maintaining patients’ mobility and research and development pipeline in extending their lives. lysosomal disorders and hereditary an- Shire’s partnerships focused on disease diagnosis include col- gioedema (HAE), noting that more pa- laborations with diagnostic companies and academic laboratories tients with those conditions will have in various countries to provide free testing for people who may access to Shire’s medicines after its pur- have HAE. chase of Baxalta Inc. Hartmann Wellhoefer “The biggest advantage in genetic diseases from Baxalta was PIPELINE PROGRESS IN HAE, HUNTER SYNDROME expanding our presence into more countries,” Wellhoefer said in a One of the most advanced programs in Shire’s genetic disease R&D Feb. 15 interview during the WORLD Symposium in San Diego. pipeline is the HAE drug candidate SHP643, a monoclonal antibody The transaction gave Shire a presence in India, where it didn’t sell that inhibits plasma kallikrein. The company acquired the potential its drugs before, expanding the company’s presence from about 60 blockbuster with its $5.9bn purchase of Dyax Corp. in late 2015. to almost 100 countries. “Demand is as big as in Europe or the US, SHP643 offers a new prophylaxis option for HAE patients via a more but access is a challenge in these countries,” he said. convenient subcutaneous injection versus Shire’s approved prophy- Even with a presence, it still takes time and patience to bring rela- lactic treatment Cinryze (C1 esterase inhibitor [human]), a twice- tively high cost medicines for rare and genetic diseases to patients weekly infusion. who haven’t had access to them before. Phase III data for SHP643 are expected around the second quar- “In rare and genetic diseases, there’s a lot of education for health ter of this year. If successful and the drug is approved, “we could be authorities to not just look at large and communicable diseases,” changing the treatment approach,” Wellhoefer said. Wellhoefer said. “There are countries that struggle to realize that it’s important to have equal access to rare disease drugs.” ‘The biggest advantage in genetic EARLY DIAGNOSIS CAN LIMIT DISEASE BURDEN diseases from Baxalta was expanding Among Shire’s many collaborations in the rare disease space, the company is working with patient groups – sometimes just a small our presence into more countries’ grouping of families whose children have a specific genetic disease – to help individuals find treatment or enroll in clinical trials. The company and the patient groups also work together to help gov- Shire also expects Phase III data this year for SHP609, an intrathe- ernments understand how many people have HAE or lysosomal cal version of Elaprase (idursulfase), the company’s enzyme replace- disorders and communicate the importance of providing treatment ment therapy (ERT) for Hunter syndrome (mucopolysaccharidosis before irreversible effects of the diseases set in. type II or MPS II). The company has a second novel ERT for Hunter Early diagnosis has become a greater focus for Shire and for the syndrome in development with partner ArmaGen Technologies lysosomal disorder research community, because new and avail- Inc. known as AGT-182; Phase I data may be available this year. Both able treatments can halt or slow progression of the disease before products are designed to cross the blood-brain barrier to treat neu- difficult symptoms take hold or before they become harder to man- rological symptoms of the disease. age. Early diagnosis was a frequent topic of discussion during the Wellhoefer said as Shire continues to look at new ways of treating WORLD (We’re Organizing Research On Lysosomal Diseases) Sym- rare and genetic diseases, the company will pursue novel technolo- posium. It’s also an area in which Shire is actively pursuing partners. gies on its own and via partnerships, such as its intrathecal R&D pro- Wellhoefer said delayed diagnosis is the biggest problem fac- grams and gene therapies. He noted that Shire gained gene therapy ing patients with lysosomal disorders, because it can take years to technology and partners via the Baxalta transaction, but said the get to a final diagnosis and by then symptoms can’t be reversed, company was investigating gene therapies prior to the merger. including severe neurological effects. For instance, Fabry disease Published online 27 February 2017

scrip.pharmamedtechbi.com 10 March 2017 | Scrip intelligence | 21 PIPELINE WATCH

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

Selected clinical trial developments for the week 24 February –2 March 2017

LEAD COMPANY/PARTNER COMPOUND INDICATION COMMENTS Phase III Suspended nonsense mutation cystic ACT CF; did not achieve primary or secondary PTC Therapeutics Inc. Translarna (ataluren) fibrosis endpoints. Updated Phase III Results ENDEAVOR; improved overall survival versus Amgen Inc. Kyprolis (carfilzomib) multiple myeloma bortezomib. levodopa-induced Adamas Pharmaceuticals Inc. Nurelin (amantadine) EASE LID 2; reduced off symptoms. dyskinesia AMAG Pharmaceuticals Inc./Palatin hypoactive sexual desire Rekynda (bremelanotide) RECONNECT; improved symptoms significantly. Technologies Inc. disorder Phase III Completed axicabtagene ciloleucel diffuse large B-Cell ZUMA-1; met primary endpoint of objective Kite Pharma Inc. (KTE-C19) lymphoma response rate . Phase III Interim/Top-line Results varicella zoster virus chickenpox, shingles 001-AM2; shingles reduced in Merck & Co. Inc. vaccine (V212) prophylaxis immunocompromised patients. CMV infection, after bone Merck & Co. Inc. letermovir Effective and lowered all-cause mortality. marrow transplant Perjeta (pertuzumab) Roche/Chugai Pharmaceutical APHINITY; met primary endpoint, reduced plus Herceptin (trastuzumab) HER-positive breast cancer Co. Ltd. invasive disease and death. and chemotherapy mild-to-moderate NOURISH AD; missed endpoints, may be due to Accera Inc. AC-1204 (caprylic acetate) Alzheimer’s disease formulation change. Sumitomo Dainippon Pharma bipolar disorder in children Latuda (lurasidone) ILLUMINATE; improved symptoms, well tolerated. Co. Ltd. and adolescents La Jolla Pharmaceutical Co. LJPC-501 (angiotensin II) hypotension/shock ATHOS-3; met primary endpoint. urinary and reproductive SOLITAIRE-U; missed endpoint but encouraging Cempra Inc. Solithera (solithromycin) tract infections results. Cempra Inc. Taksta (fusidic acid) skin infections Study 301; achieved primary endpoint . Phase III Initiated BeyondSpring Inc. plinabulin febrile neutropenia Associated with docetaxel therapy. rovalpituzumab tesirine MERU; after platinum-based chemo, as AbbVie Inc. small cell lung cancer (Rova-T) maintenance therapy. Myovant Sciences Ltd. relugolix, oral once-daily advanced prostate cancer HERO; Current therapies are injected. Phase III Announced chronic obstructive pulmo- Theravance Biopharma Inc. revefenacin A peak inspiratory flow rate study. nary disease Genentech Inc./AC Immune SA crenezumab Alzheimer’s disease CREAD2; in prodromal or mild disease. Mundipharma International Corp. Ltd. MR308 moderate to severe pain STARDOM2. Sanofi/Lexicon Pharmaceuticals Inc. sotagliflozin type 2 diabetes Combined with metformin or a sulfonylurea. Source: Biomedtracker

22 | Scrip intelligence | 10 March 2017 © Informa UK Ltd 2017 APPOINTMENTS

Sanofi’s board of directors has proposed Oliveto was president and CEO of Chelsea tical industry, Matushansky was professor the appointments of Melanie Lee and Therapeutics and also served as CEO of Gal- at the Columia University Medical Center. Bernard Charlès as new independent di- leon Pharmaceuticals. He began his career rectors. Lee is chief scientific officer at BTG at Hoffmann-La Roche Inc., where he held GW Pharmaceuticals Plc. has named Plc and previously spent 10 years at Glaxo/ various senior positions for 18 years. Scott Giacobello chief financial officer GlaxoWellcome. In 1998, she was executive (CFO) to be based at the company’s US director of research at Celltech plc, which was Mark Foletta has joined Tocagen Inc. as headquarters in Carlsbad, California. GW’s acquired by UCB, where she became execu- executive vice president and chief financial former CFO, Adam George, has been ap- tive vice president of R&D. Lee was also pre- officer. He will be succeeding the compa- pointed to the newly created role of man- viously CEO at Syntaxin Ltd and in 2014 she ny’s co-founder, Tom Darcy, who is retiring aging director, UK. Giacobello brings 25 founded NightstaRx Ltd. Since 2016, Charlès but will continue to serve on the compa- years of finance and operational experience has been vice chair and CEO of Dassault Sys- ny’s board of directors. With more than 30 to the company and previously he was CFO tèmes, he joined the company in 1983 and years of experience as a financial executive, for Chase Pharmaceuticals Corporation. Be- was appointed strategy director for R&D. Foletta was previously senior vice president fore Chase, he held senior level finance po- and chief financial officer at Amylin Pharma- sitions at Allergan Inc., most recently as vice Richard L. Wang has been appointed CEO ceuticals Inc. for over a decade. He is on the president of finance for global R&D. of Fosun Kite Biotechnology Co., Ltd.’s. board for various biopharmaceutical compa- Wang has previously held leadership roles nies, including AMN Healthcare Inc., Regulus Dynacure, a new biotechnology company at Procter & Gamble, Bristol-Myers Squibb, Therapeutics Inc. and DexCom Inc.; and also focused on rare disorders, has appointed AstraZeneca plc and GlaxoSmithKline Plc. chairs each of their audit committees. Stephane van Rooijen CEO, Frédéric Most recently, he was chief operating of- Legros chief operating officer and Leen ficer of Cellular Biomedicine Group and Hookipa Biotech AG has named Igor Thielemans head of development. The before this Wang was senior site leader and Matushansky global head, research and company, which was founded in 2016 as head of operations for GlaxoSmithKline re- development. He joins the company from a spin-off from the IGBMC (Institute of Ge- search and development in Shanghai. Daiichi Sankyo, where he was the global netic and Molecular and Cellular Biology) head of translational development for on- of Strasbourg, has also named the mem- Milestone Pharmaceuticals USA Inc. cology. Prior to this he was global head bers of its board of directors, they include: has appointed Joseph G. Oliveto president for clinical and scientific development at Frederic Chereau, Chris Mirabelli and and CEO – effective immediately. Founder Novartis’s gene & cell therapy unit as well Brett Monia, who have been appointed and former CEO, Philippe Douville, will as a global clinical program lead within the as independent directors; Rémi Droller now assume the newly created position company’s oncology translational medi- and Vanessa Malier, who represent Kurma of chief scientific officer. Before Milestone, cine unit. Before entering the pharmaceu- Partners; and new CEO van Rooijen. Scrip ELEANOR MALONE @SCRIPELEANOR LUCIE ELLIS @SCRIPLUCIE YING HUANG [email protected] [email protected] [email protected] ALEXANDRA SHIMMINGS @SCRIPALEXS LUBNA AHMED @SCRIPLUBNA JUNG-WON SHIN [email protected] [email protected] [email protected] SUKAINA.VIRJI @SCRIPSUKI PAUL WILKINSON @PAUL__WILKINSON BRIAN YANG [email protected] [email protected] [email protected] ANJU.GHANGURDE @SCRIPANJUG JOHN HODGSON @SCRIPJOHN [email protected] [email protected] All stock images in this publication MANDY JACKSON @SCRIPMANDY MIKE WARD @SCRIPMIKEWARD courtesy of www.shutterstock.com [email protected] [email protected] unless otherwise stated. JOANNE SHORTHOUSE @SCRIPJO PETER CHARLISH @PETERCHARLISH Customer Services [email protected] [email protected] Tel: +44 (0)20 7017 5540 FRANCESCA BRUCE @SCRIPFRANCESCA JOHN DAVIS @JOHN023DAVIS or (US) Toll Free: 1 800 997 3892 [email protected] [email protected] Email: [email protected] STEN STOVALL @STENSTOVALL EMILY HAYES @EMILYKATEHAYES [email protected] [email protected] To subscribe, visit IAN SCHOFIELD @SCRIPIANS JESSICA MERRILL @JESSCIAMERRILL scrip.pharmamedtechbi.com [email protected] [email protected] To advertise, contact ASHLEY YEO @ASHLEYPYEO JOSEPH HAAS [email protected] [email protected] [email protected] Scrip is published by Informa UK Limited. MARY JO LAFFLER IAN HAYDOCK ©Informa UK Ltd 2017: All rights reserved. [email protected] [email protected] ISSN 0143 7690.

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