Pfizer Decides Against A Split GSK’s Mature Products Head: What’s A Fair Price For A Biosimilar Pfizer’s decision not to break up into Innovation Still Possible In Europe? two companies reflects an improved Richard Saynor talks about the What kind of discounts are considered growth outlook. Now it can get on generics business, challenges and reasonable & what returns should with business (p3) how GSK is different (p4) companies expect? (p20)

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Scripscrip.pharmamedtechbi.com Pharma intelligence | informa four other new drugs have recently launched – Johnson & Johnson/Genmab AS’ Darzalex (daratumumab), Bristol-Myers Squibb Co.’s Empliciti (elotuzumab), Takeda’s Ninlaro (ixa- zomib), an oral follow-on to Velcade, and No- vartis AG’s Farydak (panobinostat). In the US and major European markets, payers are cognizant of the costs associated with treating multiple myeloma and the availability of a number of good options is giving them more leverage, reimbursement experts said in a Sept. 21 webinar on payer perspectives in the space.

US MARKET SET TO ROCKET The multiple myeloma market in the US overshadows the other key world markets and has been growing at a healthy pace. Shutterstock: Shutterstock: Vatel Elya Datamonitor Healthcare estimates that be- tween 2015 and 2021, US sales will grow by over 50% from $5.5bn to $7.9bn. The patent Multiple Myeloma Would Make expirations of Velcade in 2017 and Revlimid after 2020 will allow for tough competition that will balance rising costs overall. Includ- Good Guinea Pig For Oncology ing the US, the five major European markets and Japan, the market for multiple myeloma Cost Control is expected to grow from $8.7bn in 2015 to $12bn in 2020, according to Datamonitor’s EMILY HAYES [email protected] April 2016 multiple myeloma market fore- cast report. With an array of high quality drugs and Takeda Pharmaceutical Co. Ltd.’s Velcade Guidelines from the National Compre- preference for stacked combo therapy in (bortezomib) and Celgene Corp.’s immuno- hensive Cancer Network advise regimens multiple myeloma, the disease is poised modulatory agents Thalomid (thalidomide) including Velcade, Revlimid or its predeces- to become a testing ground for cost con- and Revlimid (lenalidomide) have tradition- sor Thalomid for first-line therapy, though tainment in oncology. ally dominated the market for multiple my- other brands are trying to break in to that eloma. But despite a relatively small patient line of treatment. Newer drugs are included ith multiple new drugs ap- population, development has been very ac- for use in the second-line or greater, as pa- proved and rising costs, multiple tive for this disease. tients relapse repeatedly (see graphic). W myeloma has emerged as a tar- In addition to newer contenders like Head-to-head trials represent one way of get for cost control and may become an Amgen Inc.’s proteasome inhibitor Kyprolis influencing payers from removing agents area to test out models for oncology gener- (carfilzomib) and Celgene’s immunomodu- from coverage, said Beth Nash, chief medi- ally, reimbursement experts say. latory follow-on Pomalyst (pomalidomide), CONTINUED ON PAGE 8

BROUGHT TO YOU BY THE EDITORS OF PHARMASIA NEWS, START-UP AND SCRIP INTELLIGENCE IN THIS ISSUE Saynor went Amgen and Novartis revealed from poacher Phase III data for a CGRP inhibitor treating episodic to game keeper GSK is working to migraine when he became establish an immuno- head of GSK’s inflammation portfolio & products extend learnings to other portfolio therapy areas 4 6 12

COVER / Multiple Myeloma Would Make Good Guinea Pig from the editor For Oncology Cost Control [email protected] 3 Stronger Together: Pfizer Decides Against A Split

After a seemingly interminable drum-roll, Pfizer has 4 Profile:GSK’s Mature Products Head Says Innovation finally announced what will happen to its estab- Still Possible In Established Drugs Business lished products business. Nothing. It will stay with the group. 6 Speed Is Everything In CGRP Race As Amgen/Novartis Reveal Phase III Data A couple of years ago speculation over big pharma groups’ plans to sell large portfolios of mature products 7 New Crohn’s Indication Puts Janssen’s Stelara On was rife. It wasn’t just Pfizer: Merck & Co apparently Equal Ground With Anti-TNFs hoped to secure $15bn by selling its portfolio to a gener- ics firm, while Sanofi’s former CEO Chris Viehbacher 10 Business Bulletin formed a plan to secure $8bn for the French group’s 11 1,000 Layoffs Expected At Novo Nordisk As US Pricing older products and GSK was open about its intention Pressures Bite to divest established products in developed markets. Back then, big pharma seemed to expect that pri- 11 Novartis Sees Disruptive Potential For Novel vate equity or generics companies would pay decent Malaria Drug money to buy a whole established products division. 12 GSK’s Immunology Strategy Edges Closer To Delivering But these are not easy businesses to acquire and optimize. They are complicated and varied, operat- 13 Allergan’s Oral CGRP Inhibitor Overlooked ing across diverse geographies and therapeutic areas 14 New Interim CAR-T Data Support Kite’s BLA with disparate facilities, supply chains and sales in- Submission Plans frastructures. And they are low-margin businesses, as well as being hard to grow in developed markets. 15 R&D Bites Abbott Labs and Baxter International showed that 16 Boehringer Gets Option To Buy ViraTherapeutics it’s easier to hang on to them and set innovation free And Cancer Virus Therapy than the other way round. 17 Amgen’s Kyprolis Miss In First-Line Myeloma Surprising, But Clinically Irrelevant

18 Policy & Regulation Briefs exclusive online content 19 Stockwatch: Regeneron Failure Could Hurt Rivals More

20 Expert View: What’s A Fair Price For A Biosimilar DMD Pipeline: After Sarepta’s First-Ever Approval, Are In Europe? Combinations Next? Several companies have DMD drug candidates waiting in the 21 Surprise Failure for Intra-Cellular’s Schizophrenia Drug wings to follow Sarepta’s Exondys 51 into the commercial market after FDA approval of the exon-skipping therapy, which could be 22 Pipeline Watch the backbone for future combination treatment regimens. 23 Appointments http://bit.ly/2cM86LO

Cystic Fibrosis Drug Sales Should Soar; VX-661/ Ivacaftor To Lead Way Sales of key cystic fibrosis drugs will jump in western economies over the next decade, driven by strong uptake of high-cost CFTR modulator therapies and longer use as life expectancies improve, according to a new report by Datamonitor Healthcare. @scripnews /scripintelligence http://bit.ly/2cMb0jW

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2 | Scrip intelligence | 7 October 2016 © Informa UK Ltd 2016 HEADLINE NEWS

Stronger Together: Pfizer Decides Against A Split The pharma giant’s decision not to break up into two separate publicly traded companies as it has been contemplating for several years reflects an improved growth outlook and the inability to unlock trapped value. Now Pfizer can finally get on with business. JESSICA MERRILL [email protected]

fizer Inc. will remain one company with two separate busi- ing that some of the blow from the news was already absorbed. In a ness units – Innovative Health and Essential Health – after statement Read said, “We believe that by operating two separate Pthe pharma giant’s board of directors and executive leader- and autonomous units within Pfizer we are already accessing many ship team determined that a split into two separate publicly trad- of the potential benefits of a split – sharper focus, increased ac- ed companies wouldn’t unlock trapped value and would result in countability and a greater sense of urgency – while also retaining less financial flexibility. the operational strength, efficiency and financial flexibility of op- The announcement Sept. 26 removes a long-standing overhang erating as a single company as compared with operating as two, for Pfizer, so that after years of indecision, the company can finally separate publicly traded companies.” move beyond the breakup story. The financial flexibility to dedicate toward business development has been one of the pros in favor of the single company approach Pfizer will generate the appropriate previously highlighted by Read. Pfizer will continue to generate the appropriate financial infor- financial information to preserve the mation to preserve the option for a split at a point in the future if business factors should change. One of the reasons Pfizer took so option for a split in the future long to come to a decision about the future structure of the com- pany was because it needed to collect the appropriate financial information for both sides of the businesses as separate entities. The outcome of the lengthy review highlights how much Pfizer Analysts largely agreed with Pfizer’s final determination. “While a has changed in the five years since investors began pushing for a no split decision may be disappointing to some investors, we agree breakup in 2011. Then, the company was hurtling over the Lipitor with the rationale,” said BMO Capital Markets analyst Alex Arfaei. “In patent cliff and reeling from the consequences. Now, Pfizer’s stock our view, there were too many uncertainties, including the inability to is trading at nearly double the value of where it was trading then extract operational and tax efficiencies, the growth prospects of the ($33.64 compared to $17.70 at the start of 2011) and its growth two separate entities and the market valuation of comparable assets.” prospects are much brighter, powered by the launch of the up and Barclay’s analyst Geoffrey Meacham said, “Pfizer had previously comer breast cancer therapy Ibrance (palbociclib) and a potential estimated that a potential separation would cost in excess of $1bn pipeline of immuno-oncology drugs. along with subsequent transactional support costs, which was not Both business units have been generating strong growth, with likely to result in significantly improved cash flows and tax efficien- Innovative Health revenues up 18% for the first six months of 2016 cies, or, more important, meaningful value creation.” versus the prior-year period and Essential Health revenues up 22%. Management had been promising investors it would reach a Innovative pharma and the cash-generating established prod- decision by the end of the year. It briefly said it would delay the ucts business have both been bolstered by acquisitions, namely decision even longer – until 2018 – when it announced the $160bn the roughly $17bn acquisition of Hospira, Inc. on the Essential mega merger with Allergan PLC last year, but then returned to the Health side and Anacor Pharmaceuticals Inc. and Medivation Inc. original timeline when the Allergan deal fell apart in April. on the innovative health side. The $14bn acquisition of Medivation, The company’s failure to invert to a friendlier tax domicile, de- which was announced in August but is yet to close, will give Pfizer spite two attempts, could also have played a hand in the decision another substantial growth driver, the prostate cancer blockbuster not to split, since tax deficiencies appear to be one of the hang ups. Xtandi (enzalutamide). Read has worked to position Pfizer as two distinct businesses – a The decision not to break up one of the world’s largest phar- high-growth innovative core and a cash-generating value business maceutical manufacturers didn’t seem to surprise investors. The – since he took over the CEO role in late 2010. He has been the company’s stock dropped 1.8% on the news, altogether a muted architect of a strategy to make Pfizer nimbler, no easy task for a response to a decision that could have resulted in more volatility. company that reported $48.85bn in sales in 2015. Analysts have been speculating Pfizer would decide against a Many of the steps the company has taken since becoming CEO, split for several months now, given the changes in the company’s from the sale of its Nutrition business, the spin-out of animal health evolving financial trajectory and comments by management. into a new company Zoetis and the new global commercial struc- During Pfizer’s second quarter sales and earnings call Aug. 2, CEO Ian ture put in place in early 2014 have all taken Pfizer closer to that goal. Read seemed to be laying the groundwork to cushion the news when While many of those actions seemed designed to lead Pfizer to- it was announced. He reminded investors that the option to split the ward an eventual split, perhaps now the path will lead Pfizer to- company would remain even if Pfizer decided against a move now. ward a leaner, higher-growth future as a single company. The company’s stock has dropped 7% since the earnings call, suggest- Published online 26 September 2016

scrip.pharmamedtechbi.com 7 October 2016 | Scrip intelligence | 3 PROFILE

GSK’s Mature Products Head Says Innovation Still Possible In Established Drugs Business LUCIE ELLIS [email protected]

Seasoned generics and intellectual prop- first generics companies, that was later sold erty expert Richard Saynor went from to Merck and eventually became Mylan. He poacher to game keeper when he became also set up the Arrow Group and sold that head of GlaxoSmithKline PLC’s estab- business – he’s a serial entrepreneur and kind lished products portfolio – tasked with of the grandfather of the generics industry. growing the company’s aging assets in new markets and protecting them from LE: What are the biggest challenges cur- erosion by new generic options. rently facing companies selling generics and mature branded products? ichard Saynor, senior vice president RS: Firstly, it’s becoming a much more and global head of classic and estab- global industry and scrutiny by regula- Rlished products at GlaxoSmithKline tors is very high. The challenge now is PLC, is responsible for teaching old dogs being able to build a global supply net- Richard Saynor new tricks; he manages aging branded work that is of good quality and cost products and explores innovative options effective – this is a common challenge for 45-year-old drugs in new markets for the LE: To what do you attribute your success across the entire industry. pharma giant. in pharma? Secondly, how do you innovate? This A portfolio containing more than 2,500 RS: I have passion and enjoy what I do. might sound like a strange question brands, GSK’s classical and established I have been lucky to find roles – or there but these are products that can still see products business covers a vast number of have been roles that have found me – growth. One example: we have invested therapy areas including respiratory, allergy, that I have really enjoyed, which helped heavily in antibiotic resistance data to help anti-infectives, CNS, dermatology and urol- me to be successful in those positions. support physician engagement around ogy. Saynor, who is based in Singapore, has People recognized that success and it anti-infectives. GSK is the largest provider led the unit since 2013. created more opportunities. I have also of anti-infectives globally, so we have a re- In the latest installment of Scrip’s execu- had fantastic mentors that put me in po- sponsibility to lead on this issue. tive profile series Saynor, who has previ- sitions I might not have put myself in, for Finally, how do we engage with payers ously held senior roles in Merck Generics example running a company at an early and prescribers? We are very keen to pursue and Sandoz International, talks to Lucie Ellis age or changing geographies and taking an access agenda and our goal is to treat about how he got into the generics busi- on new challenges. more patients with high quality products. ness, challenges facing the industry and how GSK is different to other off-patent LE: Who is your biggest influence and why? LE: Where does the classic and established drug developers. RS: I had really good professors at univer- products portfolio fit in at GSK? sity and they gave me a generalist view RS: GSK has a very diverse portfolio of ma- LUCIE ELLIS: What led you into the rather than a very specialist view – this ture brands, many of which are around 35- industry? has been a common theme throughout 45 years old but still class leaders in their RICHARD SAYNOR: It was accidental. I my career. However, when I was younger therapy areas. It’s down to the team to get trained as a pharmacist but I did a ‘sand- my childhood hero was Surgeon-Captain the most out of those products through life wich’ degree at university and as a part of Richard Jolly OBE, the chief medical officer cycle management. By that we mean how that I had a work placement at Roche. Dur- during the Falklands Campaign. He was we can open up these products and drive ing that time I did two-week placements quite a character being a commander and access, particularly in the emerging mar- in different departments all over the com- a medic; he was a real boy’s hero. Jolly was kets. Furthermore we have to think about pany – this gave me a great oversight of the only person in that campaign to be how we can evolve these established the industry and it was my first taste of the decorated by both the Argentinians and brands, for example through presentation business side of things. I had a particular the British. One of the things I had wanted changes and product extensions. We have interest, from this experience, in sales and to do out of university was join the army – to ensure these then feed back into manu- marketing and my roles in pharma grew but pharmacy wasn’t the best for a career facturing and supply chain, and align all of from this. Up until my placement at Roche in the armed forces so I ended up following this with the wider GSK strategy. It’s a large I was heading for a career in a hospital or another route into the pharma industry. portion of GSK’s base business and the retail pharmacy but I saw a very different Later on in my career Tony Tabatznik was established product portfolio is still very perspective during my work placement. a big influence for me. He set up one of the dynamic with more than 2,500 brands and

4 | Scrip intelligence | 7 October 2016 © Informa UK Ltd 2016 PROFILE

we treat more patients globally than any their mature business and branded gener- and see them become number one prod- other multinational company. ics. GSK was always a company I had ad- ucts in places like India, which has tradi- mired, the timing was right and colleagues tionally been seen as the most aggressively LE: How important is this area of the from past positions that I thought very generic market in the world, I think that is business? highly of were also now working at GSK. The incredible. So I’m very proud of that. RS: In the emerging markets GSK’s estab- position also allows me to stay in Asia, which lished products business is still a strong was something I was very keen to do. LE: And what about your most difficult growth unit. It is a significant contributor moment? of value to GSK and covers a large propor- LE: What are your own long term RS: The toughest moment was when I was tion of patients the company reaches. The aspirations? CEO of a company in the UK and I had to established brands portfolio is effectively RS: Right now, GSK is a very big, exciting close one of the manufacturing sites. At the foundation that allows GSK to develop business and the more we look at this ma- the time I was in my early thirties, having to and launch new products. In a number of ture products space the more opportuni- sit down with a few hundred people and markets some of these products are the ties we see. The scope and breadth of what tell them they didn’t have a job anymore number one brand still despite their pat- we support has continued to grow. GSK was incredibly difficult. While there was a ents having expired a number of years ago has recently changed the way it engages commercial rationale, the human conse- – they are strong brands that are still grow- with healthcare practitioners (HCPs) to quence was hard. ing today in their own right. bring in digital aspects and to find innova- tive ways to work with markets and pre- LE: What was the last thing you changed LE: What is the company’s long-term plan scribers – so this is an exciting time for GSK your mind about in a business decision? for this area of business? and me in my current role. For the first time RS: I suppose it would be around a couple RS: To continue to grow and support the the industry has realized it is not just about of products that traditionally we wouldn’t wider business. There is an ever growing your ability to have a sales force – it’s about have supported. I came to GSK to expand number of patients for these products in having the right connectivity. The next few the branded generics business and initially respiratory, anti-infectives, urology, derma- years for classic and established products that plan wasn’t successful. However, we tology… it’s a very broad portfolio. We seek will be a very interesting period. did see opportunity for some of the brands life-cycle changes and development chang- we already owned; with a little bit of re- es to be able to continue to grow the unit LE: If you were starting over what’s the source you can get phenomenal results. and we are still innovators in this area. How- best bit of advice you would give to your GSK now has the capability to manage ever we also have to align this with being younger self? mature assets in a different way to some of able to keep prices low enough to compete. RS: Take more risks earlier on. I wish I had its competitors and this capability has now worked overseas sooner in my career. It’s become an integral part of GSK’s business. LE: Does GSK do anything different in this always easy at the time to rationalize not area compared to its competitors? taking some opportunities, whether it’s LE: What current trend in your field would RS: We have done a lot over the last few personal or career reasons, but really it’s the you highlight as the most exciting? years to build up our internal capabilities calculated risks that you take that open up RS: Mature products are growing – maybe and to find ways to engage with physicians the best opportunities. not as much in the US – they are not all and healthcare professionals in a much declining, particularly in areas like Eastern more coordinated way. Most of the content LE: If you weren’t a pharma executive, Europe and the emerging markets. globally to support these brands comes out what would you be? of Mumbai and we engage with thousands RS: I would like to be an entrepreneur: if LE: Tell us one myth about the industry of physicians through digital platforms. I have a regret it is not setting up my own that you’d like to set straight. We have also built-up a cross functional company and running my own business. RS: Ultimately the industry does a lot more team – for medical, regulatory, supply good than it is credited for. It’s a business chain and quality – who really support LE: What has been your proudest moment? and we make money out of people being these brands. It’s almost a unique organiza- RS: My career has been a story of two sick and that is emotionally challenging tion within GSK that allows the business to halves: the first half I spent challenging pat- – but GSK tries very hard to do the right focus on its core assets but allows us to also ents and launching generics against innova- thing and treat patients in the right way. grow and treat more patients and drive a tor companies like GSK; the second half has We as a company try to find that balance strong return. seen me as poacher turned to game keeper between being a business and doing the I suppose, as I grow some of those off-pat- right thing for our patients. The industry LE: How did you get into this particular ent brands. For me some of that growth, doesn’t get great press, for example all the position? particularly in emerging markets, has been concerns right now around price goug- RS: I was approached by GSK while working incredible. Patients are at the heart of this ing, but GSK wants to grow its business in Singapore for a large, international gener- industry and we are managing now to treat by treating more patients, not by treating ics company – I was running their emerging more patients than ever. The fact that we fewer patients at a higher price. markets business – to look at heading up can take products that are 35-40 years old Published online 26 September 2016 scrip.pharmamedtechbi.com 7 October 2016 | Scrip intelligence | 5 HEADLINE NEWS

Speed Is Everything In CGRP Race As Amgen/Novartis Reveal Phase III Data Amgen and Novartis revealed the first set of Phase III data for a CGRP inhibitor in the treatment of episodic migraine, potentially positioning the companies’ biologic erenumab at the head of the drug class. MANDY JACKSON [email protected]

our development programs are neck-and-neck in the race to OPTIONS NEEDED FOR PREVENTION bring a calcitonin gene-related peptide (CGRP) inhibitor to “The positive results from ARISE are especially encouraging, be- Fmarket, and Amgen Inc. is the first company – with its partner cause there are currently no treatment options specifically de- Novartis AG – to report positive Phase III results for their biologic ere- signed for the prevention of migraine,” Novartis global head of numab (AMG 334) in episodic headache sufferers. drug development and chief medical officer Vasant Narasimhan Speed of development is key, because Amgen and Novartis said in a statement about the erenumab results in which he noted may have to be the first anti-CGRP developers to commercialize a the global need for an effective preventative migraine therapy. product in order to capture the largest migraine market share. The The World Health Organization has called migraine headaches data for CGRP inhibitors to date have been comparable, so a first- one of the top 10 causes of years lived with disability for men and to-market advantage could be the winning strategy, unless future women. People who experience episodic migraines spend about Phase III data for one of the other three monoclonal antibodies in half of each month – 14 days – with debilitating headaches. development reveals a differentiated product or if oral anti-CGRP Amgen and Novartis partnered on the development of erenum- drugs become a greater threat. ab a year ago when the companies agreed to swap rights in various markets for the Amgen-owned CGRP inhibitor and Novartis’s early- stage Alzheimer’s drug CNP520, a beta-site APP-cleaving enzyme-1 (BACE) inhibitor. The companies have since reported data that – some analysts say – may not differentiate erenumab from the Alder, Lilly and Teva biologics. In fact, Informa Pharma Intelligence’s Biomedtracker not- ed on Sept. 28 in its review of the top-line ARISE data: “the change in monthly migraine days in episodic migraine patients (with a slightly higher average of 11.4 monthly migraine days) in the Phase IIb -022 trial of TEV-48125 is perhaps slightly more impressive than that reported here.”

Shutterstock: Sergey Mironov Sergey Shutterstock: A DIFFERENTIATED PRODUCT? MAYBE, MAYBE NOT Biomedtracker raised the likelihood of US FDA approval (LOA) for ere- With their first set of Phase III data in hand, Amgen and Novartis numab by 1% to 58%, which is 6% above average for Phase III central seem to be winning the anti-CGRP contest at the moment, but Al- nervous system drugs, despite the possibility that Teva has a more der BioPharmaceuticals Inc., Eli Lilly & Co. and Teva Pharmaceutical effective episodic migraine medicine. Biomedtracker’s LOA for Teva’s Industries Ltd. are not far behind. Each company has a monoclonal biologic – without seeing any Phase III data – is 56% and for Alder’s antibody in Phase III development that has shown impressive – and ALD403 the LOA is 59%. impressively similar – results in mid-stage clinical trials. “The modest change in monthly migraine days from base- The Phase III ARISE clinical trial enrolled 577 people who expe- line compared to placebo reported [in ARISE] is encouraging for rienced migraines on four to 14 days of each month or eight days the 24-week STRIVE study evaluating 70mg and 140mg in the on average. The patients were treated with a once-monthly subcu- same (episodic migraine) patient population,” the Biomedtracker taneous injection of 70mg of erenumab or a placebo. The number analysis said. “These data complement the statistically significant of migraine days fell by 2.9 days in the erenumab arm of the trial change in monthly migraine days previously reported in chronic after 12 weeks of treatment and by 1.8 days in the placebo arm – a migraine patients.” statistically significant result. Barclays analyst Geoff Meacham also praised Amgen’s and No- Amgen and Novartis described erenumab’s side effects as simi- vartis’s preliminary ARISE results in a Sept. 28 report while noting lar to those observed in prior clinical trials. Upper respiratory tract that erenumab still may lack differentiating data. infections, injection site pain and nasopharyngitis were the most “One area where Amgen could have a competitive edge is ere- common adverse events. numab’s low dropout rate, which his- Amgen expects to complete the Phase III STRIVE clinical trial by torically was 3% versus 12% for Lilly’s CLICK the end of this year, which will provide 24-week placebo-controlled galcanezumab and 11% for Teva’s TEV- Read full story at: results for 70mg and 140mg doses of erenumab in the treatment 48125,” Meacham wrote. http://bit.ly/2dJGBPY of episodic migraine. Published online 29 September 2016

6 | Scrip intelligence | 7 October 2016 © Informa UK Ltd 2016 HEADLINE NEWS

New Crohn’s Indication Puts Janssen’s Stelara On Equal Ground With Anti-TNFs MANDY JACKSON [email protected]

J&J’s Janssen Biotech subsidiary won FDA approval for the IL-12/ However, a Janssen executive noted in March when the company IL-23 inhibitor Stelara to treat Crohn’s disease, giving it a second- reported Phase III results for Stelara that the biggest unmet need in line position alongside anti-TNF therapies for patients in need of the disease is for patients who failed or couldn’t tolerate TNF inhibi- new options. tors – a large and growing group. The company didn’t test Stelara in a head-to-head pivotal trial with one of the anti-TNF biologics, but the S FDA approval for Janssen Biotech Inc.’s Stelara (ustekinum- IL-12/23 inhibitor showed significant responses in patients who failed ab) for the treatment of Crohn’s disease puts the interleukin or couldn’t tolerate treatment with a TNF inhibitor. U12 (IL-12) and IL-23 inhibitor on equal second-line footing with anti-tumor necrosis factor (TNF) therapies – the indication’s INDICATION-BASED PRICING OFFERS leading class of biologics. COMPETITIVE OPPORTUNITY Janssen, a Johnson & Johnson subsidiary, noted that Stelara is the Stelara could benefit – with its novel mechanism and its efficacy in a first drug targeting IL-12 and IL-23 that’s approved to treat Crohn’s. But few specific diseases, including in TNF-refractory patients – from new while more than 30 potential new therapies are being developed to US payer reimbursement schemes for inflammatory diseases. treat the disease, TNF inhibitors will be Stelara’s biggest competition. Express Scripts Holding Co. revealed earlier this month that it will However, the Janssen product could be somewhat insulated from TNF negotiate 2017 pricing on a per-indication basis rather than a per-drug inhibitor biosimilars and sales could be helped by indication-based basis for therapies approved to treat seven inflammatory diseases, in- pricing for inflammatory diseases, given the need for second-line cluding Crohn’s disease. One of the goals is to remove the advantage Crohn’s therapies. that medicines approved for several indications have over therapies The FDA approved Stelara to treat adults with moderately to se- approved in just a few indications, especially when drugs in the latter verely active Crohn’s disease who’ve failed or can’t tolerate immuno- category may be safer or more effective in specific diseases. If so, bio- modulatory agents or corticosteroids, but never failed treatment with similars may not have an advantage under indication-based pricing, if a TNF inhibitor, as well as patients who failed or were intolerant to one reimbursement is weighted toward efficacy for a given indication rath- or more anti-TNF drugs. er than price. Indication-based pricing may be moot for biosimilars, The label gives physicians the option of prescribing Stelara before however, since ongoing patent litigation makes it uncertain when the or instead of a TNF inhibitor for patients who didn’t respond well to lower-cost biologics will hit the market in the US, despite recent FDA immunomodulators and steroids or who couldn’t stomach the side ef- approvals. Amgen Inc.’s Humira biosimilar Amjevita won FDA approval fects of the first-line treatments. on Sept. 23, but it could take years for AbbVie’s patent lawsuit against The language seems to give the IL-23/IL-12 blocker a slight advan- the company to be resolved. But while it may take years for Stelara to tage over integrin inhibitors – Takeda Pharmaceutical Co. Ltd.’s Entyvio feel an impact from biosimilar competition in Crohn’s disease, there are (vedolizumab) and Biogen’s Tysabri (natalizumab) – since it specifically several new therapies clamoring for a position in the underserved mar- indicates use in patients who haven’t failed treatment with a TNF in- ket. Biomedtracker, an Informa Pharma Intelligence service, lists five ac- hibitor. However, the Entyvio label does leave room for treatment of tive Phase III programs for novel Crohn’s treatments in its database. biologic-naïve Crohn’s patients, since it can be prescribed to individu- Published online 26 September 2016 als who’ve failed or couldn’t tolerate a TNF inhibitor or a corticosteroid. Later-Stage Crohn’s Pipeline OVERCOMING PRESCRIBERS’ COMFORT WITH DRUG LEAD COMPANY PARTNER MOA ANTI-TNFS Stem cell Cx601 TiGenix NV Takeda AbbVie Inc.’s best-selling TNF inhibitor Humira (adalimumab) is ap- therapy proved to treat Crohn’s, as are two of Humira’s anti-TNF competitors Integrin – J&J’s own Remicade (infliximab) and UCB Group’sCimzia (certoli- Etrolizumab Roche None Alpha-4 beta-7 zumab). The drug class has been approved for Crohn’s since 1998 inhibitor when Remicade was the first TNF inhibitor okayed for the inflamma- Nogra GED 0301 Celgene Corp. Smad inhibitor tory bowel disease. Pharma Ltd. Unfortunately for Stelara, that means that anti-TNF drugs have well- RedHill established safety and efficacy in the eyes of prescribers and not just in RHB-104 None Antibacterial Biopharma Ltd. Crohn’s, but across multiple autoimmune and inflammatory diseases, Xifaxan including rheumatoid arthritis. Stelara has been on the market for a Valeant (rifaximin) Alfa Wassermann while too, since it was approved in 2009 for psoriasis and 2013 for pso- Pharmaceuticals Antibacterial delayed SPA riatic arthritis, but it still has fewer years on the market and fewer indica- International Inc. release tions than the TNF inhibitors.

scrip.pharmamedtechbi.com 7 October 2016 | Scrip intelligence | 7 HEADLINE NEWS

CONTINUED FROM COVER cal officer at the reimbursement intelligence Treatment pathway for MM – patients experience several relapses company RealEndpoints, in the webinar. With Velcade generics on the horizon, Am- Active multiple myeloma patients gen has taken on that challenge and tested Kyprolis head-to-head against Velcade. The Not eligible for Eligible for SCT SCT strategy was successful in the second-line • Velcade-based regimens ENDEAVOR study, in which Kyprolis was as- • Velcade-based regimens Primary therapy Induction therapy • Velcade/Revlimid • Velcade/Thalomid sociated with a significant progression-free • Velcade/Revlimid followed by SCT • Revlimid • Revlimid • Thalomid survival benefit over Velcade. But the firm Revlimid suffered a setback with the failure of the first- Maintenance therapy Thalomid Velcade line CLARION study, which tested Kyprolis with melphalan and prednisone against Second line therapy or relapsed or refractory multiple myeloma • Velcade Velcade and the same background regimen • Kyprolis /Revlimid/DM in newly-diagnosed patients. Amgen ar- • Empliciti /Revlimid/DM • Ninlaro/Revlimid/DM gues that the particular regimen used in the Third and later lines of therapy • Revlimid/DM • Farydak/Velcade/DM study is not used very much anymore and DM = dexamethasone; SCT = stem cell therapy • Pomalyst /DM that results from the first-line, head-to-head Source: NCCN, Informa ENDURANCE study, which is funded by the National Cancer Institute, are still pending. “We believe multiple myeloma will be time with increased scrutiny on high costs. The CLARION trial failure is damaging, one of the first battlegrounds for payers to Payers increasingly are looking at standard- however, in that it highlights the lack of control costs in oncology. Multiple myelo- ized oncology treatment “pathways” to differentiation on efficacy compared to a ma, we believe, will give payers an unusual direct patients to the most cost-effective drug that will soon be generic. ENDEAVOR opportunity to try to implement cost-con- care. With pathways, physicians are offered has also been criticized for the use of a high trol measures,” Nash said. incentives, including ease of prescribing, dose of Kyprolis and a dose of Velcade that is Commercial payers are considering to adhere to a particular order of therapy. not commonly used in practice and associ- new payment models, including bundled Physicians may use other agents if they ated with more neuropathy. payments. choose, but it might not be in their finan- In the government sector, the US Cen- cial self-interest, Nash said. STACKED COMBOS, ters for Medicare and Medicaid Services Nash noted that effective Sept. 1, Anthem STACKED COSTS has proposed an oncology care model that Inc., formerly called WellPoint, put in place a US clinicians want to use the best therapies offers incentives for controlling costs of pathway for myeloma that guides clinicians available, which often means combinations intravenous agents so that physicians no to use Kyprolis/Revlimid/dexamethasone of three or even four drugs. Better efficacy longer are incentivized to prescribe higher- (dex) or Velcade/dex/cyclophosphamide in and safety with new drugs means patients priced products. second-line+ myeloma. Third-line options stay on therapy longer, Nash noted during The US system is very fragmented, with are Darzalex or Empliciti/Revlimid/dexa- the webinar. some drugs are covered under the phar- methasone. The myeloma pathway is part During a session on myeloma at the 2015 macy benefit and others under the medical of a larger pathway program that could save ASCO meeting, clinicians expressed aware- benefit – which makes it harder to control 3% to 4% of costs. ness of the high cost of stacked therapies costs of combinations. For example, in my- After Velcade goes off patent, the avail- and called for development of better bio- eloma, Revlimid, Pomalyst and Ninlaro are ability of generics will be an attractive markers to help avoid waste in the system, covered under the pharmacy benefit, while option in various clinical pathways, Nash but said that if a combination proved to be Velcade, Darzalex, Empliciti are covered un- added. curative in the frontline setting “almost any der the medical benefit. Cost-effective analyses and value frame- cost may be acceptable.” When drugs covered under the medical works are increasingly attracting attention. Traditionally there have been no restric- benefit show sufficient safety, some payers A typical way to measure cost-effectiveness tions on physicians in oncology, but payers are moving them into the pharmacy benefit is whether a drug offers has value in the are beginning to push back in the face of an to exert a bit more control, Nash noted. In range of $50,000 to $150,000 per quality ad- aging population and rising costs, Nash said. general in oncology, there has been a lot of justed life year (QALY). “Cancer, which had been totally immune hesitance in the US market to actually limit Myeloma has been one of the areas ana- from management by payers within the US, physicians’ choice, Nash said. lyzed by the nonprofit Institute for Clinical is no longer immune,” she said. Some insurers – like Aetna Inc. and Ex- and Economic Review, which recently re- Payers are absolutely concerned about press Scripts Holding Co. – have said that leased a value framework review of drugs cancer in general and of myeloma in par- step therapy would be difficult to apply for second-line myeloma. It found that Em- ticular and some are beginning to look for in oncology and particularly in myeloma pliciti/Revlimid/dex has a cost-effectiveness ways to slow down the spending through as appropriate sequencing of therapies is ratio of $255,000 per QALY, Kyprolis/Rev- experiments with cost control, she said. still uncertain, but this could change over limid/dex has a ratio of about $267,000 per

8 | Scrip intelligence | 7 October 2016 © Informa UK Ltd 2016 HEADLINE NEWS

QALY and Ninlaro/Revlimid/dex has a ratio Revlimid is a “complete nightmare for the Considering Farydak, the commission of about $391,000 per QALY. health insurance funds,” Tijana Ignjatovic, found the benefit-risk ratio lacking and the During a Sept. 23 meeting sponsored by lead analyst in market access at Datamoni- drug is only reimbursed at 30%. Ignjatovic the International Society for Pharmacoeco- tor Healthcare, noted during the Informa commented that this is “quite a surprise for nomic and Outcomes Research, which is webinar. oncology drugs, which usually get reim- working on some recommendations for val- Reimbursement policy varies depend- bursed at 100%.” ue frameworks on drugs and other medical ing on the country and may involve health What is more worrying, however, is the technologies, Dan Ollendorf, chief science technology assessments at the national “lukewarm assessment” by the transparency officer for ICER, noted that while working on level. In some countries, like Germany – the commission of Kyprolis with Revlimid in sec- its myeloma assessment, the patient com- largest market, with $863.8m in sales for ond-line myeloma, due to the lack of overall munity was vocal about the need for mul- 2015 – reimbursement is more tightly man- survival data and increased cardiac adverse tiple treatments with different mechanisms aged from the top, whereas in others, like events. Due to the assessment, Datamonitor of action because of issues with resistance. Italy and Spain, regional access hurdles are believes that Kyprolis will face difficult price The patient groups were saying that, “at more of an issue. negotiations until more data are available to this point with the evidence as it is, relative “Often we see disparities between differ- support use. clinical benefit between the newer regi- ent regions in one country,” Ignjatovic said. As for Pomalyst, a risk-sharing deal is in mens is not that important to us in compari- The UK’s National Institute for Health and place whereby the manufacturer refunds son to making sure that they’re all available Care Excellence (NICE), which controls ac- costs for patients who do not respond to to us … even if one of them might be seen cess for England and Wales via the National therapy. Similarly, in Italy, the manufacturer as of lesser clinical benefit than another.” Health Service, has restricted access for a only gets reimbursed for Pomalyst when pa- Other frameworks that have been de- number of drugs for multiple myeloma, tients respond. veloped include Memorial Sloan Kettering including rejecting Pomalyst for third-line Cancer Center’s DrugAbacus, which allows treatment on cost grounds, and implement- FUTURE OUTLOOK IN EUROPE users to apply their own value measures, ed risk-sharing schemes. Ignjatovic expects that “Velcade’s patent ex- a tool from ASCO, and RealEndpoints’ Rx- An outcome-based risk sharing agree- piry in 2017 will have a profound impact on Scorecard. RealEndpoints’ technology also ment was put in place early on for Velcade, the price benchmarks and reimbursement provides the basis for DrugAbacus. whereby the drug is not continued after in Europe” for multiple myeloma drugs. Manufacturers may have to use value four cycles if less than a partial response is Furthermore, she expects more deals frameworks to differentiate their products. achieved, in which case the manufacturer tied to real-world use and more risk-sharing They can’t just get a drug approved by FDA offers full rebates for costs. agreements in the future. Similarly, there will and have clear sailing, Nash said. For second-line myeloma in the UK, com- also be a continued trend in some countries monly used combinations include Thalo- to align use for patients with characteristics EUROPE ON GUARD mid/cyclophosphamide/dexmamethasone similar to those who participated in clinical Interviews by Datamonitor with payers and Velcade/cyclophosphamide/dexameth- trials – so drugs tested in broader popula- in Europe suggest rising concern about asone, regimens that are not generally in use tions may have an easier time securing re- the introduction of new drugs and asso- in other countries (see graphic). imbursement. ciated costs. In France, a national transparency com- The analyst also notes that PFS and RR as A German payer said that the introduc- mission assesses medical benefit, and its endpoints may not be sufficient to secure tion of the combination of Empliciti with findings have an impact on reimbursement. positive health technology assessments that support the sponsor’s desired price. Differing reimbursement decisions have impacted prescribing patterns Combinations will be reimbursed only Top three regimens used for second-line treatment of SCT-eligible multiple myeloma patients, by country if there is strong evidence of benefit and

60% drugs that are used in later lines of therapy where there is higher unmet need will have 50% 10% a better chance at securing reimbursement, 40% 7% the analyst said. 10% 8% 30% 9% 13% A more cost-conscious, competitive en- 8% 17% 6% 5% vironment means sponsors should be pre- 20% 11% 32% 8% 7% pared to compromise more on price. 11% 25% 10% Market Access & Reimbursement: Inside 15% 13% 14% 13% 8% 0% The Payer Perspective On Multiple Myeloma US Japan France Germany Italy Spain UK For more information, check out the re- I Revlimid + dex I Velcade + Revlimid + dex I Velcade + cyclophosphamide + dex cent complimentary webinar from Informa I Velcade + dex I Revlimid + cyclophosphamide + dex I Thalomid + cyclophosphamide + dex Pharma Intelligence’s Datamonitor Health- I Kyprolis + Revlimid + dex I Kyprolis + dex I Velcade + melphalan + prednisone I Revlimid + low-dose dex + Thalomid care and the reimbursement consultants at Source: Datamonitor Healthcare and Real Endpoints RealEndpoints. Published online 28 September 2016 scrip.pharmamedtechbi.com 7 October 2016 | Scrip intelligence | 9 BUSINESS BULLETIN

Clever Marketing Needed To Position J&J’s New Cipla Sees Changed Profile; Psoriasis Drug Ahead Of Wraps Up Europe Revamp Cheaper Options Cipla Ltd.’s management sees the firm’s profile changing as it scales up its Johnson & Johnson’s anti-interleu- US business with new launches and a step-up in product filing intensity. kin-23 therapy, guselkumab, has pro- The Indian company is also “largely done” with a restructuring in Europe duced stronger efficacy data in VOY- that saw a significant cutback in personnel but is expected to make the AGE 1, the first ever Phase III study to European business profit-accretive. Cipla admitted its smaller presence directly compare an IL inhibitor against in the US compared with certain Indian peers may be dragging down its anti-TNF-alpha treatment Humira in earnings, but expects its recent acquisition there, a ramp up in product fil- psoriasis patients – but uptake might ings and new product roll-outs to change things. At the firm’s 80th annual still be a challenge in the early treat- general meeting in Mumbai, Cipla’s managing director and global CEO, ment setting because of the number Umang Vohra, said that the company currently derives less than 20% of of cheaper alternatives on the market. its revenues from the US, which is why its “aggregate profit” when com- J&J is aiming to position guselkumab pared to the peer set may seem low. “It’s really a business mix issue. Not early in the psoriasis treatment algo- having US business in our mix, which is very profitable for other compa- rithm by directly comparing it to the nies, brings down our EBITDA [earnings before interest, tax, depreciation current standard of care (Humira) in and amortization] ratio,” said Vohra in response to a shareholder query its Phase III program but guselkumab on what was “pulling the company down.” Peers like Lupin Ltd. and Dr. will face several barriers upon launch, Reddy’s Laboratories Ltd. respectively raked in about 43% and 53% of their such as the increasing availability of revenues from the US in 2015-16. About 40% of Cipla revenues come from lower cost anti-TNF biosimilars that the Indian market, while emerging markets and South Africa are the other will likely be used in early lines of large chunks. Cipla hopes to grow its India business to $1bn levels from therapy, and the increasing availabil- around $800m currently, the CEO said. Vohra, who recently took over the ity of highly efficacious IL inhibitors. baton from outgoing global CEO Subhanu Saxena, talked of Cipla’s ac- Datamonitor Healthcare analyst Anna quisition of the US-based firms InvaGen Pharmaceuticals Inc. and Exelan Reyes told Scrip that guselkumab’s su- Pharmaceuticals Inc. and how the company plans to file several products periority versus Humira in the VOY- in the US. AGE 1 Phase III study represents a win [email protected], 29th September 2016 to J&J. However, she said the company would have to “invest heavily in order to drive guselkumab’s uptake in an “We look at therapeutic areas mul- attempt to protect its dermatology tinational pharmas are largely inter- franchise, now that many IL inhibitors GtreeBNT Aims To ested in. The drug candidates should (including Novartis AG’s anti-IL17a have novel therapeutic mechanisms,” agent Cosentyx (secukinumab), Valeant Validate Business Model Via GtreeBNT CEO Won Suk Yang told a Pharmaceuticals International Inc.’s Licensing Deals recent bio investment forum in Seoul. anti-IL17 Siliq (brodalumab) and Ab- bVie’s anti-IL23 product risankizumab South Korea’s GtreeBNT Co. Ltd. “As we are small, we can’t handle areas (ABBV-066)) have demonstrated su- is preparing or proceeding with late that require huge investment in clini- periority to J&J’s own marketed pso- stage clinical trials in the US for its cal development. We are only selecting riasis drug, Stelara.” Reyes added that drug development pipeline, while ex- candidates that require less than 600 leading dermatologists have suggested ploring licensing out opportunities to subjects in Phase III trials.” GtreeBNT, J&J may market guselkumab over the validate its business model and help originally established as a multimedia anti-IL12/IL23 product Stelara (usteki- it grow into a more globalized opera- software venture firm, started diver- numab) once the new IL-23 inhibitor is tion. The venture has a differentiated sifying into the biopharma business approved. J&J is expected to file regu- business model of acquiring rights to in 2014. Since then, the company has latory applications for guselkumab by novel drug candidates in Phase I or II completed a Phase III trial for a dry eye the end of the year in the US and Eu- development, mainly from struggling syndrome (DES) drug in the first half rope. The company is also due to pre- US biotechs or non-profit research in- of this year and begun a second Phase sent more Phase III data for guselkum- stitutes, and then taking these through III program in the US through its local ab from its VOYAGE 2 and NAVIGATE to the NDA stage and licensing them development arm.. studies in the fourth quarter. out. Its main therapeutic focus is on [email protected], [email protected], 1 October2016 rare diseases and ophthalmic disorders. 27 September 2016

10 | Scrip intelligence | 7 October 2016 © Informa UK Ltd 2016 HEADLINE NEWS

1,000 Layoffs Expected At Novo Nordisk As US Pricing Pressures Bite LUCIE ELLIS [email protected]

As a parting gift to Novo Nordisk staff, outgoing CEO Lars Re- The cuts are one of several actions Novo Nordisk has implement- bien Sørensen has announced 1,000 job cuts at the company – ed in recent months in order to reduce operating costs; other initia- around half in its home country of Denmark – in order to create a tives include a hiring freeze and restrictions on travel. “sustainable balance between income and costs” in preparation Mike Rulis, senior vice president of corporate communications for a challenging 2017. and stakeholder engagement, told Scrip: “We are facing lower prices in the US in 2017 and as the US accounts for more than ovo Nordisk AS plans to cut approximately 1,000 jobs – half of our worldwide sales, we need to bring our costs down to affecting R&D units, headquarter staff and other positions a level that matches the income we expect. This unfortunately Nin the global commercial organization – in preparation for a requires layoffs as personnel-related costs are the highest single tough 2017, in which the company is expecting increased competi- cost in the company.” tion on the US diabetes market, its largest market by sales. Incoming CEO Jørgensen told Scrip in a recent interview that the Lars Rebien Sørensen – who said in a Sept. 29 announcement level of payer pressure and competition in the diabetes market re- that job cuts were a “difficult decision to make” – will step down as mains the company’s number one challenge. However, “We have CEO of Novo Nordisk by the end of the year, with current executive the most innovative portfolio. This means we can drive volume by vice president and corporate development head Lars Fruergaard market share and also by seeking slightly higher prices for these in- Jørgensen set to succeed him in the role. novative products that have strong, differentiated profiles for treat- Sørensen said the layoffs, around 500 of which are expected to ing people with diabetes,” he said. be in Denmark, are necessary in order for the company to have a Novo Nordisk has four product launches coming up in the next “sustainable balance between income and costs.” Novo Nordisk has couple of years including the anticipated launch of its best-in-class close to half of all its employees in Denmark, including all head- GLP-1 product semaglutide. quarter staff functions. The company’s total global headcount is The company declined to comment on whether the forthcom- approximately 42,300. ing job cuts would affect management positions or R&D staff in He said: “In the current situation, we have to prioritize invest- particular development areas. Novo Nordisk also said it could not ments in key product launches that will bring innovation to pa- disclose its target cost-reduction figure at this time. tients and drive our future growth.” Published online 29 September 2016 Novartis Sees Disruptive Potential For Novel Malaria Drug Encouraging early data for a first-in-class anti malarial from Novartis suggest it is effective against the two major malaria parasites and could be a “game-changer” in the disease. ALEX SHIMMINGS [email protected]

ew data for the first product in a potential new class of an- misinin, which quickly kills the parasite, with a longer-acting partner timalarial agents, Novartis Institute for Tropical Diseases’s drug, such as mefloquine, lumefantrine (as in Novartis’s Coartem), NKAF156, showed it has activity in patients with both uncom- piperaquine, amodiaquine and pyronaridine. But rising resistance to plicated Plasmodium falciparum and P vivax malaria, including arte- artemisinin and decreasing partner drug efficacy, particularly in south- misinin-resistant parasites, and without any evident safety concerns. east Asia, is now threatening control of the disease, heightening the The data, just published in the New England Journal of Medicine, need for new therapies. KAF156 is one of two drugs to have come suggest the product could form a vital pillar in the fight against in- out of Novartis’s malaria research program (the other being KAE609 creasing resistance to current therapies for the disease. “KAF156 is a (cipargamin)), which the company plans to combine with other part- potential game-changing therapy against malaria,” said Thierry Dia- ner drugs to produce new combinations with multiple mechanisms of gana, head of the Novartis Institute for Tropical Diseases (NITD).”It acts action to minimize the against the two main parasites responsible for the majority of malaria risk of drug resistance, CLICK deaths and against the blood and liver stages of the parasite’s lifecycle.” Diagana said. Read full story at: Artemisinin-based combination therapies (ACTs) are currently the Published online http://bit.ly/2cXh9bq standard of care against P falciparum infections. They combine arte- 26 September 2016

scrip.pharmamedtechbi.com 7 October 2016 | Scrip intelligence | 11 HEADLINE NEWS

GSK’s Immunology Strategy Edges Closer To Delivering JESSICA MERRILL [email protected]

GlaxoSmithKline is working to establish tor (BLyS), was hailed as the first new drug an immuno-inflammation portfolio and for lupus in 50 years when it launched in extend learnings to other therapy areas. 2011 for systemic lupus erythematosus, Sirukumab could be GSK’s first new prod- but it failed to meet early commercial ex- uct in I&I beyond Benlysta. Chief immu- pectations. Benlysta’s moderate efficacy nology Officer Paul-Peter Tak outlined his tempered sales; it generated just £209m strategy in an interview with Scrip. in 2015, leaps and bounds lower than the $5bn in sales some analysts had forecast est known for developing respiratory the drug would generate in 2016 at the drugs, HIV medicines and vaccines, time it launched. The slower-than-expect- BGlaxoSmithKline PLC has ambitions ed launch led to the demise of HGS, when to become an immuno-inflammation pow- GSK took advantage of the opportunity to erhouse. A five-year initiative to establish a buy out its partner. pipeline of drugs in the area could deliver GSK also announced Sept. 23 that it filed its first product to the commercial market a BLA in the US and marketing authoriza- next year. GSK Chief Immunology Officer Paul-Peter Tak tion application extension in Europe for a GSK announced Sept. 23 that a BLA for new subcutaneous formula of Benlysta in the human anti-interleukin-6 (IL-6) anti- York. “During the last five years, I think the two presentations, a single-dose prefilled body sirukumab was filed with FDA for the immuno-inflammation portfolio has come syringe and a single-dose autoinjector. The treatment of moderate to severe rheuma- together into a strategic and synergistic current formula is administered intrave- toid arthritis. The drug, in development portfolio for a whole variety of diseases.” nously. The company is also running trials under a collaboration with Janssen Biotech The size of the team dedicated to I&I has testing Benlysta in new indications. Inc., could be the company’s first new drug grown, although not substantially. Most of Tak believes sirukumab and Benlysta will in immuno-inflammation beyond Benlysta the focus has been on reprioritizing human be anchors for an emerging pipeline of drugs (belimumab), which GSK acquired in 2012 resources to high-priority projects. The I&I to follow, some discovered internally at GSK with the $3.6bn acquisition of Human Ge- unit – incorporating everything from early and others by partners. The goal is to launch nome Sciences Inc. discovery to late-stage drug development sirukumab as a complement to Benlysta, tar- GSK’s chief immunology officer Paul- – includes about 220 people. geting rheumatology practices to firmly es- Peter Tak has been tasked with driving im- “During the first six months after I arrived, tablish the I&I commercial organization and munological research at the big pharma. I terminated 40% of the programs, thereby then follow up with newer novel medicines. The company is about to enter a new I could release the resources, including the Sirukumab is not a first-in-class agent phase as Emma Walmsley, currently head headcount, to work on very specific and fo- and will likely be the third IL-6 inhibitor to of Consumer Healthcare, takes over for Sir cused programs that are all consistent with reach the market, behind Roche’s market- Andrew Witty as CEO next year. The insider the strategy,” Tak said. ed Actemra (tocilizumab) and Regeneron appointment is viewed as a commitment The budget has grown because the Pharmaceuticals Inc./Sanofi’s sarilumab, to the current growth strategy. portfolio has matured. “There was noth- pending at FDA with an Oct. 30 action A rheumatologist by training, Tak joined ing we had in the portfolio except Ben- date. The launch could be a challenging the company in 2011, transitioning from a lysta that was even candidate-selected five one given the competitive dynamics in the career in academia. He worked as professor years ago and now we have quite a lot in RA market and the fact that Phase III data of medicine and chair of the Department the clinic,” Tak added. for sirukumab suggest the product might of Clinical Immunology & Rheumatology at have inferior efficacy to Actemra and sari- the Academic Medical Centre/University of SIRUKUMAB AND BENLYSTA lumab when it comes to ACR20 responses, Amsterdam prior to joining GSK as head of WILL ANCHOR THE BUDDING a standard measure used in trials. Immunology & Inflammation. PIPELINE But Tak insists the decision to partner on In January, Tak was promoted to chief Among Tak’s first priorities after joining GSK a known mechanism like sirukumab was by immunology officer, extending oversight were to bring a late-stage drug into the I&I design. “You want to build a presence in the of immunological research in other thera- portfolio and explore new opportunities for field with medicines that are very likely to py areas, like immuno-oncology, dermatol- Benlysta, approved for lupus. On the first or- work, and then after that bring very disrup- ogy and infectious diseases. der of business, GSK partnered with Janssen tive medicines [to market],” he said. “Not all “Over the last several years, we have in- on sirukumab in December 2011, bringing of them are going to make it. Some of them creasingly invested in immuno-inflamma- in a Phase III-ready asset for RA. will fall over, but some of them will be com- tion, and I would say more generally im- Meanwhile, Benlysta, a first-in-class anti- pletely transformative, we believe, and they munology,” Tak said in an interview in New body that inhibits B-lymphocyte stimula- will be blockbusters as well,” he added.

12 | Scrip intelligence | 7 October 2016 © Informa UK Ltd 2016 HEADLINE NEWS

Tak believes sirukumab may have ing of two infusions in two weeks of Ritux- some advantages over the competition an,” Tak said. The company is also exploring Allergan’s Oral because the drugs are slightly different. the regimen for the treatment of SLE. CGRP Inhibitor Sirukumab targets the IL-6 cytokine, while Actemra and sarilumab target the IL-6 NOVEL MECHANISMS Overlooked receptor. Sirukumab has demonstrated IN THE CLINIC benefits to patients when dosed every GSK has several novel drugs in earlier stag- Allergan PLC’s oral small molecules four weeks via subcutaneous injection, es of development in I&I. In Phase II, GSK ubrogepant and atogepant – in-li- while labeling for Actemra recommends is studying the granulocyte-macrophage censed from Merck & Co. Inc. in 2015 weekly dosing and sarilumab was dosed colony-stimulating factor (GM-CSF) cyto- – may be overlooked contenders in the every other week in the pivotal trials sup- kine GSK3196165 in patients with inflam- race to bring a calcitonin gene-related porting the regulatory filing. matory hand osteoarthritis (HOA). The peptide (CGRP) inhibitor to the mar- With Benlysta, GSK is looking to expand drug is one that GSK in-licensed in from ket for migraine headaches. the drug to new indications, building off MorphoSys AG in 2013. Tak described OA The four leaders in the anti-CGRP the knowledge the drug works in lupus, an as a big unmet medical need and com- field – Amgen Inc. with Novartis AG, Al- der BioPharmaceuticals Inc., Eli Lilly & autoantibody-dependent autoimmune dis- mercial opportunity because the disease Co. and Teva Pharmaceutical Industries ease. SLE is characterized by high circulating impacts about 10% of the general popula- Ltd. – are developing monoclonal anti- autoantibodies, which are produced by B- tion and no disease-modifying drugs are bodies. But if Allergan’s two drugs can cells and can trigger inflammatory damage. approved for the condition. meet or beat the injectable medicines, or “If Benlysta works in autoantibody-de- Another drug Tak is energized about is just come close to the biologics’ efficacy, pendent disease that manifests itself as the GSK2982772, a RIP1 kinase inhibitor that the oral alternatives are likely to grab a signs and symptoms of SLE, then it is quite was developed internally and recently en- sizeable portion of CGRP inhibitor sales likely that it may also work in other diseases tered the clinic. RIP1 plays a key role in a va- and significantly increase the company’s driven by autoantibodies,” Tak said. “In the riety of diseases, including TNF-mediated presence in the migraine market beyond first year, I started a strategic plan to go into diseases like RA and inflammatory bowel Botox (onabotulinumtoxinA). other diseases that are dependent on au- disease, as well as diseases characterized “There are four monoclonal antibod- toantibodies.” by apoptosis, he said. GSK is moving devel- ies in development, but we have the lead One indication GSK is exploring now is opment forward aggressively, opting to ini- in developing oral CGRP antagonists,” Sjögren’s syndrome, an immune disorder tiate three Phase II studies testing the drug Allergan Chief Research and Develop- driven by autoantibodies that results in dry in parallel in patients with RA, psoriasis and ment Officer David Nicholson said in eyes and dry mouth. ulcerative colitis. The studies initiated in an interview with Scrip. “We’d rather be September. in a leading position with oral com- “I will know at the end of next year prob- pounds than one of several [developers] ‘I terminated 40% of ably what the best indications are,” Tak said. with injectables.” The executive is also aiming to keep GSK the programs, thereby However, Amgen and Novartis are involved in early and novel research by poised to lead the CGRP inhibition fostering relationships with biotech start- I could release the field, since they recently were the first of ups and academia, relying on a variety of the monoclonal antibody developers to resources, including mechanisms. One is the European venture release top-line Phase III results. Aller- firm Medicxi Ventures that GSK backs and the headcount’ gan only started its Phase III studies for on which Tak sits on the scientific advisory ubrogepant within the past few months. board. Another is DPAc (Discovery Partner- Allergan paid Merck $250m up front “If you look at the official epidemiology, ships with Academia), through which GSK in July 2015 for the rights to Merck’s it is relatively rare, but I am absolutely con- collaborates with academics. oral CGRP inhibitors. The two lead vinced it is not rare,” said Tak. “Patients are Tak has also established something assets include ubrogepant, which is un- complaining about dry mouth and dry called the Immunology Network, which der investigation in separate Phase III eyes and many of them are depressed and has two components: a board of external clinical trials enrolling 1,350 patients have fatigue and it is easy to miss, so it is immunology academics from different each to treat acute migraines at the underdiagnosed.” backgrounds that advise GSK and a catalyst onset of a headache. GSK is testing Benlysta in a Phase II trial in sabbatical program to embed academic [email protected], patients with Sjögren’s syndrome, testing scientists in GSK’s labs. 30 September 2016 both belimumab as a monotherapy and in GSK’s immuno-inflammation research combination with Roche’s anti-CD20 anti- has come a long way in five years, but the body Rituxan (rituximab). true test will be getting new drugs to mar- CLICK “There is a very strong theoretical ratio- ket and establishing them as commercially Read full story at: nale that you might optimize the use of successful franchises. http://bit.ly/2dDRlzm Benlysta by just one single course, consist- Published online 27 September 2016 scrip.pharmamedtechbi.com 7 October 2016 | Scrip intelligence | 13 HEADLINE NEWS

New Interim CAR-T Data Support Kite’s BLA Submission Plans MANDY JACKSON [email protected]

Kite Pharma Inc. executives reiterated plans on Sept. 26 to pur- a five-fold improvement over existing therapy. This is what made us sue US FDA approval this year for the chimeric antigen receptor T very reassured with the interim [Phase II ZUMA-1] data.” cell (CAR-T) therapy known as KTE-C19, keeping the company on The response rates show that Kite’s training program for clinical track to seek accelerated approval for a form of advanced lym- trial sites and investigators regarding the logistics of manufacturing phoma before any of its competitors. and delivering KTE-C19 to patients paid off. “We did a lot of pre-work and we were reassured that the sites anta Monica, California-based Kite reported interim data from were quick to learn to deliver cell therapy and manage adverse the Phase II portion of its Phase I/II clinical trial known as ZUMA- events,” Chang said. “For the first time, we have a clear demonstra- S1, which showed three-month response rates that were fairly tion that cell therapy could be used at multiple sites.” consistent with results in the Phase I portion of the trial. Chair, presi- Most of the clinical trial locations were hematology and oncolo- dent and CEO Arie Belldegrun and chief medical officer David Chang gy centers that have experience treating cancer patients with bone told Scrip that Kite will disclose more specific timing for its biologic marrow transplantation, he noted. license application (BLA) submission after the company shares the Kite reported two patient deaths – one from hemophagocytic interim results with the FDA. That meeting is expected to occur with- lymphohistiocytosis and one from cardiac arrest – in Phase II of in the next month. ZUMA-1, both of which were related to cytokine release syndrome Belldegrun was particularly pleased with the consistency of the (CRS), a common adverse event for CAR-T therapies. Phase I and II results in ZUMA-1, because the company changed its The most common grade 3 or higher adverse events across all 62 manufacturing process and expanded the study from the National patients were neutropenia (66%), anemia (40%), febrile neutrope- Cancer Institute (NCI) to more than 20 clinical sites, yet generated an nia (29%), thrombocytopenia (29%) and encephalopathy (26%) as overall response rate (ORR) and complete response (CR) rate in Phase well as neurological toxicity (18%) and CRS (34%). II at numbers reasonably close to the Phase I three-month results. Notably, the two deaths associated with KTE-C19 were associ- ZUMA-1 Phase II Results Show Consistent Data ated with CRS and not neurological toxicity. One of Kite’s two main competitors, Juno Therapeutics Inc., has reported at least four pa- DLBCL TFL/PMBCL COMBINED tient deaths in one of the clinical trials for its lead CD19-targeting ORR (%) CR (%) ORR (%) CR (%) ORR (%) CR (%) product candidate. The setback pushed Juno’s BLA submission for ORR 76 47 91 73 79 52 JCAR015 to sometime after Kite’s late 2016 submission and Novartis Month 3 39 33 64 64 44 39 AG’s early 2017 BLA for CTL019. “We’re carefully reviewing the adverse events [in ZUMA-1’s Phase II],” Chang said. “These are heavily treated patients with chemo-refrac- ZUMA-1 enrolled patients non-Hodgkin lymphoma (NHL) across both phases of the study that were refractory to treatment with the tory disease. In these patients, treatment-related deaths will occur.” chemotherapy standard of care. The Phase I portion included sev- Kite will report more Phase II safety and efficacy data later this en patients who had diffuse large B cell lymphoma (DLBCL) who year, possibly during the American Society of Hematology’s annual had an ORR of 71% and CR of 57% initially, dropping to a 43% ORR meeting in December, but Chang said he doesn’t think the two and 43% CR at three months, which were unchanged at six to nine CRS-related deaths will add regulatory risk. months after treatment with KTE-C19. “The overall benefit/risk, from what we are seeing, is still strongly The CAR-T therapy involves extraction and reengineering of pa- on the positive side,” he said. tients’ T cells so that they are designed to attack cancer cells that Biomedtracker, an Informa Pharma Intelligence analyst service, express the antigen CD19. also viewed the interim Phase II results as positive and potentially Response rates were higher in Phase II of ZUMA-1 for the 11 supportive of FDA approval, raising the likelihood of approval by patients with transformed follicular lymphoma (TFL) and primary 2% to 16%, which was 6% above average for cancer therapies in mediastinal B cell lymphoma (PMBCL) than for the 51 patients with early clinical development. DLBCL, but the combined ORR and CR (n=62) were comparable “We are still waiting for the primary endpoint of this trial, the six- with the small Phase I population (see table below). month response rate,” the Biomedtracker analysis said. “If the CR While the Phase II ORR and CR of 39% and 33%, respectively, rate in Phase II does not drop off at six months, Kite will have a among DLBCL patients were below the 43% overall and complete strong case for early approval.” responses in Phase I, the numbers remain well above the CR of Kite gained more than 10% in after-hours trading following the 8% that Kite saw among more than 600 NHL patients treated with interim data announcement, reaching $60.60 per share versus the chemotherapy in the observational SCHOLAR-1 study. “You have Sept. 26 closing price of $54.98. to look at the patient population studied,” Chang said. “This is nearly Published online 27 September 2016

14 | Scrip intelligence | 7 October 2016 © Informa UK Ltd 2016 R&D BITES

GeNeuro’s Causal Approach To MS Treatment Gathers Array Rises As COLUMBUS Clears Phase Momentum III Melanoma Hurdle GeNeuro has hit the halfway mark of its Early data from the Phase III COLUMBUS study looking at a combina- proof-of-concept trial ahead of sched- tion of Array BioPharma Inc.’s BRAF inhibitor encorafenib (LGX818) ule, recently enrolling the 130th patient and MEK inhibitor binimetinib (MEK162) proved positive, sending the in the CHANGE-MS Phase IIb study company’s stock price soaring, though more information is needed to of GNbAC1 in patients with relapsing- assess the competitive prospects for what would be the third BRAF/ remitting multiple sclerosis (RRMS). MEK inhibitor duo to market. Top-line data from the first part of the GNbAC1 is a monoclonal antibody Phase III study in patients with BRAF-mutant advanced, unresectable designed to neutralize MSRV-Env, a or metastatic melanoma met its primary endpoint, significantly im- human endogenous retroviral (HERV) proving progression-free survival (PFS) with encorafenib/binimetinib genetic element that is silent in healthy compared with Roche/Genentech Inc.’s BRAF inhibitor Zelboraf (vemu- people but ubiquitously expressed in rafenib) alone. The news sent Array’s share price up by 81% to close at MS lesions. These elements are nor- $6.61 on Sept. 27 on NASDAQ, even though the products will be enter- mally highly repressed, but the MSRV- ing an increasingly crowded market. In the multinational study, 1,577 Env protein is commonly detected in patients were randomized to receive 450 mg encorafenib plus 45 mg MS lesions. “It was difficult for people binimetinib, or 300 mg encorafenib alone, or 960 mg vemurafenib. The median PFS for patients treated with the combination of encorafenib plus binimetinib was 14.9 months versus 7.3 months for patients treated with vemurafenib (p<0.001). However, the secondary endpoint analysis comparing the combination to patients treated with encorafenib alone showed a median PFS of 14.9 months versus 9.6 months (p=0.051), a non-significant difference. The combination was generally well-tolerated with adverse events consistent with previous combination encorafenib plus binimetinib clinical trial results in BRAF-mutant melanoma pa-

Shutterstock: toeytoey Shutterstock: tients, Array said. [email protected], 27 September 2016 to take us seriously at the beginning,” admitted GeNeuro CEO Jesús Martin- Garcia. “The minute you said ‘retrovi- tion of 17% in patients taking placebo rus,’ people would say: ‘been there, done (p=0.0047). Furthermore, patients tak- that, doesn’t work.’ But technology Dravet Syndrome Sets GW ing Epidiolex 10 mg/kg/day achieved has moved on.” MSRV-Env has been Pharma Apart In Epilepsy a median reduction in monthly drop shown to activate the toll-like receptor seizures of 37% compared with a reduc- 4 (TLR4) pathway, a component of the GW Pharma’s stock spiked at 811p on tion of 17% in patients taking placebo innate immune system, and has been Sept. 26 – its highest value this year (p=0.0016). GW also reported posi- proposed as a causal trigger to the neu- on the London Stock Exchange – fol- tive data from another Phase III study roinflammation and neurodegenera- lowing the publication of the third set in LGS patients in June this year, and tion seen in MS. GeNeuro believes that of positive Phase III data this year for from a Phase III trial in patients with by neutralizing MSRV-Env, GNbAC1 Epidiolex in rare forms of pediatric epi- Dravet syndrome in March. The com- could block a key factor promoting the lepsy. However, Epidiolex’s potential in pany plans to file the drug for both in- inflammation on the plaques, as well as Dravet syndrome will be its competi- dications in a single application in the allowing the remyelination repair pro- tive edge to set GW apart from rivals. first half of 2017. Stephen Schultz, vice cess to restart. The trial is being done in The most recent data from a second president of investor relations at GW RRMS patients “as we wanted to look at Phase III study in in patients with Len- Pharma, told Scrip: “We are focused the inflammatory component and neu- nox-Gastaut syndrome (LGS), a rare on getting Epidiolex approved in the rodegenerative component,” which was and severe form of childhood-onset US and Europe, and on growing our also why it was important to GeNeuro epilepsy, showed that those treated commercial organization to be able to test the compound against placebo, with Epidiolex 20 mg/kg/day achieved to successfully bring this new drug to Martin-Garcia told Scrip. a median reduction in monthly drop market.” [email protected], seizures (ie, those that make people [email protected], 29 September 2016 fall) of 42% compared with a reduc- 27 September 2016 scrip.pharmamedtechbi.com 7 October 2016 | Scrip intelligence | 15 HEADLINE NEWS

Boehringer Gets Option To Buy Surprise Boehringer ViraTherapeutics And Cancer Virus Decision Turns Therapy Hanmi Investors’ JESSICA MERRILL [email protected] Hopes To Despair The German pharma agreed to pay up to integrate into the DNA and has been modi- €210m to investigate ViraTherapeutics’ fied to avoid neural inflammation associated lead candidate, VSV-GP, alone and in with wild type viruses. Additionally, the gly- combination, with an option to buy Vira- coprotein of the virus has been replaced by Therapeutics depending on the outcome the glycoprotein of a different virus, the Lym- of Phase I studies. phocytic Choriomeningitis Virus (LCMV), to

conceal the virus from the immune system. Dmitry Kutlayev Shutterstock: oehringer Ingelheim GMBH is invest- In preclinical models it did not induce virus What a day for Hanmi Pharmaceuti- ing further in the Austrian cancer start- neutralizing antibodies, potentially enabling cal Co. Ltd.’s investors. They must Bup ViraTherapeutics in a deal that will repeated administration, the firms said. have thought they were in for a rally give the German pharma access to a next- The goal of oncolytic virus therapy is to after the South Korean pharma firm generation oncolytic virus therapy platform use a virus to infect and break down cancer made an announcement of a hefty and lead candidate VSV-GP (vesicular sto- cells, so that tumor antigens normally hid- licensing out deal with Genentech matitis virus glycoprotein), along with an den from the immune system inside the Inc. on Sept. 29. But their hopes soon option to buyout ViraTherapeutics outright. cells are released, triggering an immune turned to disappointment. In the deal announced Sept. 28, Boeh- response to fight the tumor. The approach Hanmi’s shares started the next day ringer agreed to pay up to €210m for the increasingly appears to hold promise as a higher, but turned sharply lower after option to buy ViraTherapeutics after VSV- way to prime and boost the immune sys- the company disclosed that Boehring- GP finishes Phase I testing. In addition, the tem to fight cancer in combination with er Ingelheim GMBH had decided to companies agreed to jointly develop a other immuno-oncology approaches, like return the rights to Hanmi’s olmutinib next-generation oncolytic virus therapy and checkpoint inhibitors. (HM61713/BI 1482694) that it had study VSV-GP alone and in combination Amgen Inc.’s Imlygic (talimogene laher- licensed in last year. with other therapies. ViraTherapeutics will parepvec) was the first genetically modified Based on its decision, Boehringer will be responsible for preclinical and Phase I oncolytic viral therapy approved by FDA in no longer conduct new clinical trials clinical testing of VSV-GP. October 2015, though the approach in gen- on olmutinib and Hanmi will retain Boehringer was already an early investor in eral has faced lots of challenges. the upfront and milestone payments ViraTherapeutics, with Boehringer Ingelheim Several other oncolytic virus programs of $65m that it has received so far. Venture Fund one of the company’s lead in- also are in development, and therapeutic The German group decided to return vestors, along with EMBL Ventures, in a €3.6m cancer vaccines are seeing a renaissance the rights taking into consideration Series A round in 2015. as potential partners to prime for other im- a reassessment of all clinical data for The privately held pharma has homed in munotherapies. Boehringer said it is inter- olmutinib, recent trends for innovative on oncology as one of its core therapy areas, ested in testing VSV-GP in combinations; the lung cancer therapies, and Boehringer’s along with diabetes and respiratory. But the company’s own oncology pipeline includes own vision for the sector, according to area of research is one in which the closely an immune checkpoint inhibitor and a can- Hanmi’s disclosure to the stock market. guarded company has acknowledged it cer vaccine. The company said the oncolytic A Hanmi spokesperson was not aware whether the South Korean would benefit from more external partner- virus offers potential for testing in combina- pharma will receive any further com- ships. Its initiatives in oncology thus far have tions with either program. The firms expect pensation from Boehringer. “As we largely centered around lung cancer. to begin Phase I testing in 2018. Boehringer have just been informed of the mat- “Oncolytic viruses are among the most currently has two marketed cancer drugs. Gi- ter, we don’t have any more informa- promising new therapy approaches in can- lotrif (afatinib) was its first, approved for EGFR tion on this,” she said. cer research and the technology developed mutation-positive non-small cell lung cancer [email protected], by ViraTherapeutics may offer significant -ad (NSCLC) in July 2013 and pending at FDA 30 September 2016 vantages compared to others currently un- and in Europe for advanced squamous cell der development,” Boehringer said. carcinoma. Its second, Vargatef (nintedanib) VSV-GP has a shorter replication time than was approved in Europe in combination with CLICK other oncolytic virus platforms in develop- docetaxel for advanced, metastatic or locally Read full story at: ment, according to the companies. Other po- recurrent NSCLC in November 2014. http://bit.ly/2dE1tIx tential advantages are that the virus does not Published online 28 Spetember 2016

16 | Scrip intelligence | 7 October 2016 © Informa UK Ltd 2016 HEADLINE NEWS

Amgen’s Kyprolis Miss In First-Line Myeloma Surprising, But Clinically Irrelevant JOSEPH HAAS [email protected]

Because CLARION was designed to test ond-line multiple myeloma setting. But Am- can Society of Hematology meeting this De- Kyprolis head-to-head against fellow gen has other opportunities to show Kyprolis’ cember, the exec added. Amgen enjoined proteasome inhibitor Velcade, the fail- superiority in the proteasome inhibitor class, three oncologists to present their opinions ure could hurt the drug’s standing in its including a Phase III investigator-sponsored of the CLARION data so far, with each saying class. But the trial design used a regi- trial (ENDURANCE) testing Kyprolis with le- the findings would not affect their clinical men largely phased out of clinical prac- nalidomide (Celgene Corp.’s Revlimid) and practice much, if at all. Ola Landgren, chief of tice and Amgen has other chances to dexamethasone (KRD) against Velcade with the myeloma service at Memorial Sloan Ket- prove superiority. the same background therapy in newly diag- tering Cancer Center, said the regimen tested nosed multiple myeloma. in the study represents current treatment of lthough the failure of Amgen Inc.’s Amgen paid $10.4bn in 2013 to acquire about 2% of the US patient base. Kyprolis to show superior progres- Onyx Pharmaceuticals Inc., with the recently “I think I have prescribed melphalan-pred- Asion-free survival in a Phase III head- approved Kyprolis the primary driver behind nisone less than 10 times in the past 10 years,” to-head trial against classmate Velcade that deal. In July, the big biotech reported the doctor noted. “It is clearly not a therapy surprised many analysts, they consistently that Kyprolis brought in $172m in global that we use here. It used to be standard in Eu- noted that the regimens used in the com- sales during the second quarter of 2016, up rope, but even there the evolution has kind parative trial are almost entirely abandoned 45% year-over-year, but the drug has not of bumped the combination aside.” in the multiple myeloma setting. been the blockbuster seller hoped for to Landgren added that the preferred The company is trying to further amelio- date, nor remunerative enough to justify the regimen for multiple myeloma at present rate the trial failure by enlisting oncologists price paid for Onyx. combines a proteasome inhibitor with an to state that the data would not affect their The treatment paradigm in multiple my- immunomodulatory drug and a low-dose ongoing use of Kyprolis. eloma is ever-changing as clinicians search steroid. Both regimens being tested in the Amgen overviewed top-line data from for the best regimen in a space that now head-to-head ENDURANCE study fit those the CLARION trial – testing Kyprolis (carfilzo- offers several therapeutic options. Revlimid parameters. mib) with melphalan and prednisone (KMP) and Velcade have been the standards, es- University of Chicago’s Andrzej Jakubow- against a regimen of Takeda Pharmaceutical pecially in the frontline setting, but there iak, who told the call he’d been involved in Co. Ltd./Johnson & Johnson’s Velcade (bort- are new challengers in the form of Takeda’s the development of Kyprolis “almost from the ezomib) with the same background therapy oral proteasome inhibitor Ninlaro (ixazomib) beginning,” said the CLARION study not only (VMP) in 955 newly diagnosed multiple my- along with antibody therapies Darzalex (da- used the wrong regimen but the wrong du- eloma patients who were ineligible for stem- ratumumab) from J&J and Genmab AS and ration of treatment as well, due to the toxicity cell transplant treatment – Sept. 27. On the Empliciti (elotuzumab) from Bristol-Myers of the melphalan-prednisone combo. With primary endpoint of progression-free survival Squibb Co. While the new competition has Kyprolis having shown superiority to Velcade (PFS), the KMP regimen yielded median PFS come in for later lines of therapy, different in previous studies, such as the second-line of 22.3 months compared to 22.1 months for drugs and combinations are looking to move trial ENDEAVOR, his confidence in the drug the VMP regimen, a difference that was not into the first-line. has not diminished, he said. statistically significant. “I have absolutely not been shaken by Amgen executive VP-research and de- CLARION DESIGN DIDN’T these results and [there is] no change in my velopment Sean Harper told a same-day REFLECT EVOLVING opinion about the importance of carfilzomib conference that data measuring overall TREATMENT LANDSCAPE for future progress and the development of a survival were not yet mature but did not in- During the investor call, Harper explained faster cure in myeloma,” he stated. dicate statistical significance either. The two that CLARION had been designed by Onyx Despite prior data indicating advantages regimens had similar and expected rates of before the 2013 buyout, and that since then for Kyprolis over Velcade, especially in the re- Grade 3 or higher adverse events (74.7% the treatment landscape in multiple myelo- fractory setting, Harper noted that it remains KPM/76.2% VPM), but the Kyprolis regimen ma has changed greatly, with melphalan- important to establish superiority in front- did show a clear advantage in avoiding the containing regimens barely used anymore line treatment. “I think until we generate Grade 2 adverse event of peripheral neu- in the US and less often than previously in such data, there will be those that will argue ropathy, with a 2.5% incidence versus 35.1% Europe. Amgen declined to elaborate on that Velcade should be used first-line from a in the Velcade arm. the CLARION data during the call, such as payer perspective,” he said. “Fortunately, that Harper called the data disappointing, es- performance on the secondary endpoint of is not a universal approach, particularly in pecially considering the advantage Kyprolis overall survival, because it hopes to present the United States.” has shown compared to Velcade in the sec- the trial as a late-breaker entry at the Ameri- Published online 27 September 2016 scrip.pharmamedtechbi.com 7 October 2016 | Scrip intelligence | 17 POLICY & REGULATION BRIEFS

Japan To Become First Market For Troubled Brodalumab Daiichi’s Japan Filing The First For The interleukin-targeting antibody Denosumab In RA brodalumab will have its first launch Following what it said were “excellent” results from a local Phase III worldwide this week, in Japan for vari- trial earlier this year, Daiichi Sankyo Co. Ltd. has submitted a market- ous forms of psoriasis. Following its ing authorization application in Japan for denosumab in the additional reimbursement price listing and in- indication of rheumatoid arthritis (RA), apparently the first globally in clusion in the national health insur- this indication. The anti-RANKL (receptor activator of nuclear kappa B ance tariff on Aug. 31, Kyowa Hakko ligand) antibody, licensed from Amgen Inc., was first launched in Japan Kirin Co. Ltd.’s Lumicef (brodalumab) as Ranmark in April 2012 for bone complications stemming from mul- tiple myeloma and bone metastases from solid tumors. It also reached the local market under the separate brand name Pralia in June 2013 as a once per six month, subcutaneously injected treatment for osteopo- rosis, based on Japanese clinical results showing reduced risk of verte- bral fracture. Ranmark added another indication, the treatment of gi- ant cell tumors of bone, in May 2014. Daiichi acquired development and marketing rights to denosumab in Japan back in 2007 from Amgen, which markets the product elsewhere as Xgeva for a range of indica- tions. Amgen completed a Phase II trial in RA some years ago but there- after did not pursue the indication, unlike its Japanese licensee. RANKL - a mediator of osteoclast formation, function and survival - activates osteoclasts and RA-linked inflammation, which can then in turn cause bone erosions. The rationale for RANKL inhibition in the disease is that this can help limit joint damage caused by such bone erosion. The DE- SIRABLE placebo-controlled Phase III clinical study program in Japan led by Daiichi looked at patients being treated with disease-modifying anti-rheumatic drug therapy. The Japanese firm announced in March

Shutterstock: Wolfilser Shutterstock: that the trial had achieved its major objective, with denosumab showing “excellent effects in preventing structural joint damage.” The primary endpoint was change from baseline in Total Sharp Score at 12 months, will be launched in Japan on Sept.30. but Daiichi Sankyo has so far not provided further details of the find- The interleukin-17 receptor A anti- ings. However, in published results from a Phase II program in Japan, body was approved in the country in denosumab significantly inhibited the progression of bone erosion at 12 early July, based on results from two months compared with placebo, and also increased bone density, when Japanese Phase III trials, for psoriasis added to standard methotrexate therapy. vulgaris, psoriatic arthritis, pustular [email protected], 26 September 2016 psoriasis and psoriatic erythroderma responding inadequately to existing first-line therapies. A US FDA adviso- ry committee in July also unanimous- be less severe than those that might the Phase III AMAGINE trial, and its ly supported the approval of broda- be adopted in the US, where several former partner AstraZeneca PLC sub- lumab (developed in this market by members of the advisory committee sequently licensed its ex-Asia rights Valeant) as Siliq, but the FDA has un- recommended that Siliq carry a black to Valeant Pharmaceuticals Interna- til Nov. 16 to make its decision on the box statement warning of potential tional Inc. Development programs in drug, meaning that the Japanese roll drug-related suicide risk and behav- other potential indications such as out will be the first globally. Kyowa ior, which was a key focus of delib- rheumatoid arthritis and Crohn’s dis- Hakko Kirin in Tokyo told Scrip that erations. Nevertheless, some analysts ease have also been suspended. In Ja- the Japanese use precautions for Lu- still see sales of $400-500m in the US pan, brodalumab was originally taken micef will include a statement advis- despite any such black box, due to the into development by the Kirin-Amgen ing doctors to prescribe the product drug’s solid efficacy, although others joint venture, but Kyowa Hakko Kirin with caution in patients with a history are less optimistic. Originator Am- acquired full rights in this and other of mental health issues or who have gen Inc. dropped brodalumab’s de- selected Asian markets in late 2010. previously attempted suicide. How- velopment in May 2015 over suicide [email protected], ever, the Japanese warnings appear to ideation and behavior events seen in 28th September 2016

18 | Scrip intelligence | 7 October 2016 © Informa UK Ltd 2016 STOCKWATCH

Regeneron Failure Could Hurt Rivals More ANDY SMITH

A Friday morning clinical trial result at all other anti-PDGF products for AMD that traocular pressure when injecting larger Regeneron had implications across a could have competed against Eylea. On volumes into the eye. The Citigroup ana- large number of companies marketing the negative side for Regeneron there are lysts also pointed out that Ophthotech’s and developing ant-VEGF and anti-PDGF the continuing costs for the second Phase Phase III studies go out to 24 weeks but drugs including Ophthotech, Allergan, II study and the higher probability that the this is also partly academic since Eylea has Roche and Novartis. Eylea franchise is now less well protected on already shown a clinically relevant 7.5 let- patent expiry. ter improvement at 12 weeks, although or some time there has been an under- The elephant in the room in the treat- the results in different clinical studies may lying debate on whether the efficacy ment of AMD by anti-angiogenic thera- be more dependent on, and easily con- Fof vascular endothelial growth factor pies like Eylea has always been the founded by, the stage at which AMD pa- (VEGF) inhibition in the treatment of wet off-label use of Avastin which can be tients are enrolled. age-related macular degeneration (AMD) reconstituted for a fraction of the price The analysts from Jefferies were more can be enhanced by the simultaneous in- of the branded and higher priced alter- circumspect in their research and in a previ- hibition of platelet-derived growth factor natives of Novartis AG /Roche’s Lucentis ous note had already sown a different seed (PDGF). At the end of last week that debate (ranibizumab), the even higher priced of doubt on Fovista. The Jefferies analysts exploded into a frenzy of attack, parry and but highest efficacy Eylea, and the now hosted a dinner with a retinal specialist who defense as supporters of companies on irrelevant and less efficacious Macugen expected the Fovista plus Lucentis Phase III both sides of the divide positioned them- (pegaptanib; OSI Pharmaceuticals Ltd./ studies that are due to report before the end selves after Regeneron Pharmaceuticals Inc. Pfizer Inc.). The attraction of an anti-PDGF of the year to show a statistically – but much reported the results of its CAPELLA Phase II approach has always been to add efficacy less clinically significant – 2 letter gain with clinical trial. over off-label Avastin and provide a value the combination. It was not clear whether Regeneron reported the failure of the proposition for the higher pricing of any the opinion leader had the antagonism ef- co-formulation of its anti-PDGF monoclo- combination. This is probably why Re- fect of PDGF antagonists against VEGF an- nal antibody rinucumab and its approved generon and Allergan PLC are developing tagonists in mind. anti-VEGF recombinant peptide Eylea dual anti-VEGF/PDGF combination prod- According to the American Academy (aflibercept) to show an improvement ucts and why, until Friday Sept. 30, the of Ophthalmology, the use of anti-VEGF over Eylea alone in 505 treatment-naive development of Ophthotech Corp. and drugs has nearly halved the incidence patients with wet AMD over 12 weeks of partner Novartis’s anti-PDGF product Fo- of AMD-related blindness in some coun- treatment. Fueling the debate further was vista (pegpleranib) – which could be ad- tries. As with most modern medical in- the result that Eylea alone performed bet- ministered after any anti-VEGF molecule, terventions, it’s that second half that is ter than the combination – an ironic echo even off-label Avastin – was a possible always the hardest. At the moment, to of the non-linear more-is-not-necessarily- worry for Regeneron and Roche. crack the hardest nut the most effica- better dose-response seen with Avastin cious (or in Europe, the cheapest) drug (bevacizumab) in some cancer indications. OPTHOTECH PLUMMETS should probably be used. After Regen- No press coverage or investment bank re- Ophthotech finished down nearly 15% on eron’s recent announcement, Fovista search I read dared to raise the specter that the day of Regeneron’s announcement (which was acquired from OSI Pharma- the inhibition of new blood vessel growth despite a spirited defense by the analysts ceuticals for next to nothing) looks like it at the back of the eye by VEGF-mediated at Citigroup who proposed five reasons will be neither. approaches could itself be interfered with why the read-through to Fovista should The Magna Biopharma Income fund by PDGF antagonism, but it seemed an be limited. I almost stopped reading at holdings include Allergan and Roche. obvious conclusion. The analysts at Cow- the first one, however, which was that Fo- en came closest when they wrote that vista is an aptamer and rinucumab is an Andy Smith is chief investment officer of CAPELLA ‘is negative for the class of anti- antibody. This argument is the opposite of Mann Bioinvest. Mann Bioinvest is the in- PDGFs alone’. the Macugen versus Lucentis reality (until vestment adviser for the Magna BioPharma The share price of Regeneron started the Eylea was approved) where the aptamer Income fund which has no position in the day down nearly 4% but as the day wore is the least efficacious product. The sec- stocks mentioned, unless stated above. Dr on, perceptions changed and it finished ond point was that Fovista is a separate Smith gives an investment fund manager’s the day down just over 1% against a 1.2% injection while Regeneron’s product is view on life science companies. He has been rise in the NASDAQ Biotech Index. There are co-formulated in a smaller injection vol- lead fund manager for four life science–spe- interpretations of the CAPELLA study that ume. It is difficult to imagine why patients cific funds, including International Biotech- are not just positive for Regeneron, but sug- would prefer two injections in their eye nology Trust and the AXA Framlington Bio- gest a strategic masterstroke. At the cost of to one and why ophthalmologists would tech Fund, and was awarded the Technology one Phase II program, Regeneron devalued not be more worried about increased in- Fund Manager of the year for 2007.

scrip.pharmamedtechbi.com 7 October 2016 | Scrip intelligence | 19 EXPERT VIEW

What’s A Fair Price For A Biosimilar In Europe? The views of biosimilar manufacturers and payers in Europe still vary widely as to what a “fair price” for a biosimilar should be, what discounts should be offered and when, and how to determine what is an appropriate return on investment, says a new report from Simon Kucher & Partners. IAN SCHOFIELD [email protected]

hat is a “fair price” for a biosimilar, Presenting the report on Sept. 23, Mi- place that “implicitly” required companies what kind of discounts are con- chael Dilger, a partner with Simon Kucher to “immediately offer a high discount in or- Wsidered reasonable at different & Partners, said that the list of criteria “may der to stay in the market” (e.g., single win- points of the product life cycle, and what not be comprehensive, but from our dis- ner tenders) whereas companies would returns should biosimilar companies expect cussions these nine came out as the most prefer moderate discounts to begin with on their investments? important for sustainability.” and price erosion over time. These are some of the questions ad- Carol Lynch, chair of the BMG and global Payers, though, countered that they do dressed in a new report looking at how to head of biopharmaceuticals at Sandoz, not always ask companies for high dis- ensure the sustainability of the European said the report showed that a sustainable counts and often industry itself offers vol- biosimilars market, produced by consul- biosimilar medicines market was one that untary price concessions of 50% or more. tancy Simon Kucher & Partners for the Bio- provided continued benefits to all stake- One payer suggested a discount of 40-50% similar Medicines Group of the European holders: increased access for patients, more was sustainable in general, but that “50- generics and biosimilars industry body, treatment options for physicians, sustain- 70%” would be more appropriate “when Medicines for Europe. ability healthcare budgets for payers, and talking about very successful drugs such as Unfortunately, it seems, the views of business opportunities for manufacturers. Enbrel, Humira etc.” manufacturers and payers differ widely on “Beyond the payer-industry relationship, Another commented that payers and many aspects of the biosimilars market, a multi-stakeholder approach is crucial to manufacturers had a very different under- prompting the report’s authors to urge the develop a sustainable biosimilar medicines standing of a “fair price level,” but added parties to try to reach a common under- market and gainsharing in particular has that it should be borne in that “payers are standing of the benefits of biosimilars in proven to be a successful driver for in- predominantly interested in the potential both the short and long term. creased utilization of biosimilar medicines savings biosimilars offer.” The report looks at experience and expec- in medical practice throughout Europe In sum, the report said, the biosimilar in- tations in seven EU/EEA countries – France, providing benefits to all stakeholders,” dustry felt moderate rebates at launch and Germany, Italy, Norway, Poland, Spain and Lynch stated. reasonable price erosion over time was the UK – focusing on pricing and market the best way forward, while payers had access policies, the impact of those policies WHAT’S A “FAIR PRICE”? high initial price expectations and were on national uptake and price, the estimated The report includes a number of remarks by influenced by price concessions offered by savings through use of biosimilars, different payers and companies interviewed by the manufacturers. purchasing practices, the effect of discounts consultancy in the various countries, includ- on savings and access, and the effects of bi- ing some interesting payer observations in COMMERCIAL osimilar use on access and treatment guide- response to manufacturers’ claims regarding ATTRACTIVENESS lines as well as health outcomes. the costs of developing biosimilars in the As for the importance of commercial at- It identifies nine criteria for the “ideal sus- context of determining price levels. tractiveness of the biosimilars market, tainable biosimilars market”: The two appear to have very different industry came out in favor of sustained • A “fair” price level. takes on what constitutes a “fair” price for a long-term profits so that it can invest in fu- • A high biosimilar market share. biosimilar, for example. ture biosimilar R&D, saying that each price • An acknowledgment during the pricing One manufacturer said biosimilar pro- discount should be matched by an appro- and market access (PMA) process of the duction involved “significant” upfront in- priate uptake in volume sales, according to high degree of complexity of biologics. vestments that needed to be balanced the report. • The need for parallel sourcing from mul- by a “reasonable” price and an appropriate But while payers agreed with the con- tiple manufacturers. speed of price erosion. Another comment- cept of long-term profitability, they were • Maintenance of healthy competition. ed that there was “no such thing” as a fair uncertain as to how to judge what is an • Commercial attractiveness of biosimilars. price, as this depended on “the respective appropriate return on investment (ROI). “I • Payer guidance on the use of biosimilars product and market environment. What is agree that investments have to be balanced versus the originator drug. considered a fair price may alter based on by income, but can’t judge whether, e.g., a • A low effort needed to monitor and en- the number of competitors and the size of 10% ROI is sufficient for manufacturers,” one force payer policies. the market.” payer commented. “But they will never pro- • Earlier and broader use of biosimilars in The industry view overall was that pay- vide us with their real cost structure. And if additional patient segments. ers in several markets had PMA policies in they did, would we believe them?”

20 | Scrip intelligence | 7 October 2016 © Informa UK Ltd 2016 EXPERT VIEW/HEADLINE NEWS

There seemed to be a fair bit of scepti- for example, allowing them to reallocate cism towards the industry’s arguments on savings to health units, and gainsharing at Surprise Failure the investments required to produce bio- physician level where doctors may split the for Intra-Cellular’s similars. One payer claimed that upfront savings with the health insurance. investments in biosimilars amounted to Gainsharing is most effective if the Schizophrenia “no more than €20-30m, and COGS (cost healthcare provider sees tangible benefits of goods sold) reflect about 2-4% of the from generated savings (additional services Drug actual BS price. That’s why I often refer to for patients, improved working conditions, A second Phase III study of Intra-Cellu- biosimilars as biogenerics.” monetary benefits, etc), the report notes. lar Therapies Inc.’s lead drug candi- Companies were also keen to stress the date, ITI-007 for schizophrenia, has UK AND GERMANY HAVE complexity (and therefore costs) of biosim- failed to replicate the promising results EFFECTIVE POLICIES ilar medicine development, production, of the first, sending the New York- It was felt, overall, that of the markets ex- supply and storage, saying this is a crucial based firm’s share price down by 63% factor with regard to price and market ac- amined, the UK and Germany already had to $15.66 on NASDAQ on Sept. 29. cess policies. pricing and market access policies in place Data from the latest (302) trial show But payers say this complexity is already that effectively supported a sustainable bio- that neither dose of the first-in-class considered in those policies. “Higher com- similars market. drug tested separated from placebo on plexity of biologics versus small molecules Germany, the report says, has: the primary endpoint measure of change is already being considered throughout • Target agreements including biosimilar from baseline on the Positive and Nega- our pricing & market access policies – for quotas perceived as core PMA policy el- tive Syndrome Scale (PANSS) total score, generics we are expecting much higher ements leveraging biosimilar uptake. in the pre-defined patient population. discounts,” was one payer comment. • A high number of sick funds creating Compounding the disappointment was Another said: “Originator manufacturers sufficient opportunities for market ac- the fact that the active control, risperi- have already argued that their products are cess (e.g., via tendering, open-house done, did separate from placebo. more complex versus small molecules. So contracts). In the trial of 696 schizophrenia complexity is already being considered in • Gainsharing at the physician association patients with an acute exacerbation of the originators’ price, which again is the start- level that supports biosimilar uptake (for psychotic symptoms, the 60 mg and 20 ing point for biosimilar price negotiations.” example KV Westfalen-Lippe and sick mg doses of ITI-007 produced a change fund Barmer GEK). from baseline on the PANSS total score COMPETITION • Information and education, which are of -14.6 points and -15.0 points respec- As for competition over the long term, pay- important for successful biosimilar im- tively versus a -15.1 point change with ers agreed that competitive behavior was plementation. placebo at six weeks. Risperidone dem- important to achieve bargaining power in The characteristics of the UK include: onstrated a change from baseline on price negotiations, but disagreed on the • Four regional tenders offer multiple busi- the PANSS total score of -20.5 points. need for multiple biosimilar manufacturers ness opportunities for biosimilar manu- In some consolation for Intra-Cellu- in the marketplace for one active substance, facturers and ensure that price discounts lar, ITI-007 was significantly better than saying it was enough if the tender winner are rewarded with an appropriate bio- risperidone on key safety and tolerabil- served the market – ie, one manufacturer similar volume/uptake. ity parameters and had a safety profile takes all. • National/regional guidance (imposed by similar to placebo. The favourable safety “Generating savings is by nature a short the HTA body NICE & Clinical Commis- profile has been pitched as a potential term thing, payers have annual budgets, and sioning Groups) recommends usage of key differentiator for the novel product. therefore they don’t look five or ten years into the most cost-effective drugs, facilitating Intra-Cellular is blaming the fail- the future where the effect of policies that biosimilar uptake. ure, at least in part, on “an unusually limit competition may be more obvious,” Dil- • Although gainsharing is not yet com- high placebo response” at some of the ger commented. If manufacturers see com- monly implemented (due to the com- study sites, although some observers petition is limited, “they may take decisions plexity of splitting savings generated pointed out that this did not seem not to invest in certain development or not between CCGs and hospitals), it is still to have unduly affected risperidone’s to launch later on in certain markets.” perceived as a promising driver of future results. “These are surprising and very The report also mentions the role of biosimilar uptake. disappointing results for Intra-Cellu- “gainsharing,” saying it has proven to be Nonetheless, the report says that in lar,” commented analysts at Informa a “successful driver of biosimilar uptake both these countries there is still room for Pharma Intelligence’s Biomedtracker. across multiple markets” with benefits for improvement and that payers “need to in- [email protected], 29 Sept 2016 all stakeholders. This includes initiatives troduce more effective biosimilar pricing such as non-cash gainsharing at the hos- and market access policies, supporting CLICK pital level (e.g., savings allow more patients improved long-term sustainability of the Read full story at: to be treated within the same budget), biosimilar business.” http://bit.ly/2doUt3m direct gainsharing in hospitals through, Published online 27 September 2016 scrip.pharmamedtechbi.com 7 October 2016 | Scrip intelligence | 21 PIPELINE WATCH

Scrip’s weekly Pipeline Watch tabulates the most recently reported CLICK late-stage clinical trial and regulatory developments from the more Visit scrip intelligence.com than 10,000 drug candidates currently under active research worldwide. for the entire pipeline with added commentary. Late-stage clinical developments for the week 23–29 September 2016

LEAD COMPANY PARTNER COMPANY DRUG INDICATION MARKET REGULATORY APPROVAL rheumatoid arthritis, psoriatic arthritis, Amgen Inc. – Amjevita (adalimumab-atto) ankylosing spondylitis, Crohn’s disease, US ulcerative colitis, plaque psoriasis Idelvion (albutrepenonacog CSL Behring – hemophilia B Japan alfa) Aegerion Pharmaceuticals – Juxtapid (lomitapide) homozygous familial hypercholesterolemia Japan Otsuka Pharmaceutical Ariad Pharmaceuticals Inc. Iclusig (ponatinib) chronic myeloid leukemia Japan Boehringer Ingelheim Micatrio (telmisartan, amlodi- Astellas Pharma Inc. hypertension Japan GMBH pine, hydrochlorothiazide) Taiho Pharmaceutical Co. Faes Farma SA Bilanoa (bilastine) allergic rhinitis, urticara, itching Japan Merck & Co. Inc. – Zepatier (elbasvir, grazoprevir) hepatitis C Japan Merck & Co Kyorin Pharmaceutical Desalex (desloratadine) allergic rhinitis, urticaria, itching Japan Merck & Co. Taiho Keytruda (pembrolizumab) melanoma Japan Asahi Kasei Corp. Novartis AG Reclast (zoledronic acid) osteoporosis Japan Otsuka Senju Pharmaceutical Mikeluna (cartelol, latanoprost) glaucoma Japan Mochida Pharmaceutical Shire PLC Lialda (mesalazine) ulcerative colitis Japan Bronchitol (mannitol) dry Pharmaxis Ltd. – cystic fibrosis Russia powder inhaler SUPPLEMENTAL REGULATORY APPROVAL Janssen Biotech Inc. – Stelara (ustekinumab) Crohn’s disease US AbbVie Inc. Eisai Co. Ltd. Humira (adalimumab) non-infectious uveitis Japan Otsuka – Abilify (aripiprazole) autism spectrum disorders Japan Vertex Pharmaceuticals – Orkambi (lumacaftor, ivacaftor) cystic fibrosis US Novartis AG – Ilaris (canakinumab) periodic fever syndromes US Otsuka Lundbeck Inc. Rexulti (brexpiprazole) schizophrenia maintenance US REGULATORY FILING ACCEPTED Amgen UCB SA romosozumab osteoporosis US Regeneron Sanofi dupilumab atopic dermatitis US Pharmaceuticals Inc. AB Science – mastinib amyotrophic lateral sclerosis EU REGULATORY FILING Janssen Biotech Inc. GlaxoSmithKline PLC sirukumab rheumatoid arthritis US SUPPLEMENTAL REGULATORY FILING GlaxoSmithKline plc – Benlysta (belimumab) sc systemic lupus disease US, EU Janssen Inc. AbbVie Imbruvica (ibrutinib) marginal zone lymphoma US Eisai – Fycompa (perampanel) epilepsy US Daiichi Sankyo Co. Ltd. Amgen Pralia (denosumab) rheumatoid arthritis Japan ROLLING NDA COMPLETED Biogen Ionis Pharmaceuticals nusinersen spinal muscular atrophy US PRODUCT LAUNCH Kyowa Hakko Kirin Co. Ltd. AstraZeneca PLC Lumicef (brodalumab) psoriasis, psoriatic arthritis Japan Source: Biomedtracker

22 | Scrip intelligence | 7 October 2016 © Informa UK Ltd 2016 APPOINTMENTS

Brian McNamara, head of Europe and College London and Duke University, North the first employees at Amicus, he held vari- Americas at GlaxoSmithKline PLC’s Con- Carolina and has published over 250 papers ous leadership roles over a 10-year period in sumer Healthcare business, has been draft- in the field. He is a recipient of the Royal program/alliance management, medical af- ed in as Emma Walmsley’s replacement Society Wolfson Research Merit Award. fairs and commercial planning. Advaxis also as the latter leaves her role as chief exec of In addition, one of the company’s non- announced that Greg Mayes, the current ex- the consumer unit to become group CEO. executive directors, Cornelia Bargmann, ecutive vice president, will be stepping into McNamara will continue as a member of the has stepped down from the board and has the role of chief business officer. board of the consumer healthcare joint ven- been appointed president of Chan Zucker- ture with Novartis and will be based in the berg Science, part of the Chan Zuckerberg Atlantic Healthcare PLC., a company fo- UK. He joined GSK’s consumer health execu- Initiative. The initiative was set up by Face- cused on gastrointestinal disorders, has ap- tive team in 2015 – previously he had been book founder Mark Zuckerberg and his wife pointed Karl Keegan chief financial officer at Novartis AG for 11 years. Priscilla Chan. (CFO). Prior to this position he held various senior positions at multiple private and pub- Sanofi has appointed Alan Main executive Shaun Clinton has been elected Clinigen licly listed companies and investment banks. vice president consumer healthcare, he will Group Plc’s CEO after Peter George, the Most recently Keegan was chief corporate be a member of the executive committee current CEO, announced that he will be development officer at Vectura Group Plc. and lead a newly created consumer health- stepping down on Nov. 11, 2016. Clinton Previously he was CFO at Pharming Group care global business unit – effective Oct. 1, has been deputy CEO since July 2015 be- NV and prior to this he served as CFO at Min- 2016. Main carries over 30 years of market- fore which he was chief operating officer for ster Pharmaceuticals Plc. ing and general management experience more than three years. In addition, Robin in the consumer health and medical device Sibson, who has been non-executive direc- fields and most recently, he was global pres- tor since 2015 and before that the Group’s Kite Pharma Inc. has appointed Christine ident, Bayer Medical Care. chief financial officer, will be retiring from Cassiano senior vice president of corporate the board in November. communications and investor relations and AstraZeneca Plc has appointed David to the company’s executive committee. Most Goldstein chief adviser genomics to lead Adavaxis Inc., a biotech focused on cancer recently, Cassiano was head of healthcare for its integrated genomics initiative. Goldstein therapies, has appointed Christopher Duke the healthcare marketing and communica- will continue in his full-time role as director senior vice president and chief operating of- tions consulting firm, W2O Group. Previously of the institute for Genomic Medicine and ficer – effective immediately. Duke carries she co-founded ARC2 Communications and professor of genetics and development at over 20 years’ experience and recently was Media and also held senior communication Columbia University Medical Center. Gold- vice president, global commercial opera- roles at biotech and pharma companies such stein previously held positions at University tions at Amicus Therapeutics Inc. As one of as Amgen, Allergan and Abraxis BioScience. Scrip ELEANOR MALONE @SCRIPELEANOR LUCIE ELLIS @SCRIPLUCIE YING HUANG [email protected] [email protected] [email protected] ALEXANDRA SHIMMINGS @SCRIPALEXS LUBNA AHMED @SCRIPLUBNA JUNG-WON SHIN [email protected] [email protected] [email protected] SUKAINA.VIRJI @SCRIPSUKI PAUL WILKINSON @PAUL__WILKINSON BRIAN YANG [email protected] [email protected] [email protected] ANJU.GHANGURDE @SCRIPANJUG JOHN HODGSON @SCRIPJOHN [email protected] [email protected] All stock images in this publication MANDY JACKSON @SCRIPMANDY MIKE WARD @SCRIPMIKEWARD courtesy of www.shutterstock.com [email protected] [email protected] unless otherwise stated. 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