Refocus, Optimize, Externalize: How To Handle Off-Label Promotion: Expert View: Cancer Drugs Fund Takeda Overhauls Global R&D A Guide From PhRMA And BIO Relaunches Under a sweeping new blueprint Industry communication principles Will pharma have to shoulder Takeda is simplifying its network offer best practices for combating additional financial risks while of internal sites to improve focus contrary evidence (p14) patients still don’t get full access and efficiency (p6) to medicines in the UK? (p19)

12 August 2016 No. 3815

Scripscripintelligence.com Pharma intelligence | informa trials that Pfizer has been running in parallel. In June, Pfizer reported data from two stud- ies, SPIRE-HR (high-risk) and SPIRE-FH (familial hypercholesterolemia), which both met their primary endpoint, demonstrating reductions in the percent change from baseline in LDL-C at 12 weeks versus placebo. Bococizumab will be behind its rivals if and when it reaches the market, but Pfizer had been hoping to have cardiovascular out- comes data in hand around the same time as the competition, which would have helped to even the playing field. The company is run- ning two cardiovascular outcomes studies, SPIRE-1 and SPIRE-2, which is testing the drug in high-risk patients. During the quarterly call, Pfizer said it expects to have cardiovascular outcomes data in the second half of 2017. Shutterstock: Pavel Kubarkov Pavel Shutterstock: Meanwhile, Amgen and Sanofi/Regeneron have moved up their timelines for reporting data. They both expect they could have data Pfizer Dashes Hopes For A PCSK9 Pill available before the end of 2016. Jessica Merrill [email protected] Pfizer may be scrapping the oral pill, but it still could wind up with different administra- Pfizer has decided not to move forward locumab) and Sanofi/Regeneron Pharma- tion for its injectable. The firm is partnered with an oral PCSK9 blocker in early clini- ceuticals Inc.’s Praluent (alirocumab), while with Halozyme Therapeutics Inc. on the cal development because the efficacy Pfizer has one in late-stage development company’s ENHANZE technology platform wouldn’t stand up to injectable rivals. called bococizumab. for bococizumab, a drug delivery technology An oral pill would have had an interest- that can allow some biologics to be dosed fizer Inc. has decided not to move for- ing competitive position versus the inject- subcutaneously. Halozyme announced in ward with the development of an oral able products, though its development was February that a Phase I trial has enrolled test- PPCSK9 inhibitor for the treatment of years off and the market dynamics for the ing bococizumab with ENHANZE. high cholesterol, president-worldwide R&D PCSK9 blockers that have launched has so Pfizer has not revealed much information Mikael Dolsten revealed during the com- far been challenging, driven largely by payer about the early stage oral program. During pany’s second quarter earnings call Aug. 2. pushback on price. The injectables cost an interview at the J.P. Morgan Healthcare “We don’t think the profile will be com- roughly $14,000 a year. conference in 2015, Dolsten spoke enthu- petitive,” Dolsten said, pointing to the Pfizer is focusing on development of boco- siastically about the opportunity and said it strong efficacy seen in Phase III clinical cizumab, and is investing significantly in the was based on “intriguing science” and that studies of the injectable PCSK9 blockers. program. The company is running six Phase III the drug lowered cholesterol substantially Two injectable PCSK9 inhibitors are already studies testing the drug’s lipid lowering abil- in animal studies. on the market, Amgen Inc.’s Repatha (evo- ity, including two cardiovascular outcomes Published online 2 August 2016

Brought to you by the editors of PharmAsia News, start-up and Scrip Intelligence in this issue

AstraZeneca’s German Merck boasts New UK Cancer Drugs MedImmune explains US sales for Gonal-f Fund reignites cost of PCSK9/GLP-1 fusion fertility treatment innovation debate diabetes therapy

11 13 19

COVER / Pfizer Dashes Hopes For A PCSK9 Pill

from the editor 3 Does CheckMate 226 Take Bristol Out Of The End Game? [email protected] 4 Merck, Allergan Suggested As Suitors But Biogen’s Takeda’s plans to transfer hundreds of R&D staff to Attractiveness Questioned an as-yet unnamed external company may offer some 5 A Split Won’t ‘Make Or Break’ Pfizer, CEO Read Says consolation to people set to lose their jobs at the Jap- anese major (see page 6). 5 GSK, Google To Invest £540m In Bioelectronics JV Nevertheless, in the longer run it may prove to be 6 Refocus, Optimize, Externalize: Takeda Overhauls more convenient for Takeda than for its divested Global R&D workers. Externalizing R&D to CROs helps reduce big pharmas’ staff overheads and institutional inef- 7 Business Bulletin ficiency. Companies can also mitigate the immedi- ate negative publicity around large-scale redundancy 8 Shire Ups Synergies Forecast, Baxalta Integration On Track programs by pointing out that they are taking action 9 Mid-Sized European Companies Eager To Acquire During to protect the interests of their workforce in finding Growth Spurt new posts for them. Merck Serono did it when it announced that at 10 R&D Bites least 100 of 500 laid-off workers would get job offers 11 MedImmune Gets Creative In Diabetes With PCSK9/GLP-1 from CRO partner Quintiles in 2013, while in 2014 Fusion Product GSK did it when it transferred 450 staff in Research Triangle Park to Parexel. However, affected employ- 12 Allergan, Gedeon Richter Unbowed By Cariprazine MDD ees face greater uncertainties. Less than a year after Phase III Trial Failure the Parexel transfer, a sizeable portion of those GSK 13 Gonal-f 2Q Sales Allow German Merck To Up Forecast workers lost their jobs once again. Sometimes the pharma company is just lobbing a ticking time bomb 14 How To Handle Off-Label Promotion: out of its own yard. A Guide From PhRMA And BIO 16 Policy & Regulation Briefs

17 Teva Advancing Two Advair Generics With Late 2017 Target exclusive online content 18 Deal Watch: Roche Aborts But Regeneron, Amgen and Pfizer Sign Up

Exelixis’ Cabometyx Signals Changing Of Guard 19 Expert View: New UK Cancer Drugs Fund Dismays In Kidney Cancer Pharma, Charities One of a trio of new drugs shaking up the kidney cancer market, Cabometyx (cabozantinib) does better than expected in its first 20 Astellas Dips Into Digital Health nine weeks on the US market. http://bit.ly/2b5EpUB 21 Stockwatch: The Art Of Strategic News Placement

CHA, Sorrento JV Highlights Korean I-O Appetite 22 Pipeline Watch Sorrento and CHA Biotech’s agreement to form a CAR-NK cell therapy joint venture is very much “on trend,” being the latest 23 Appointments in a recent series of immuno-oncology collaborations between Korean and foreign firms. http://bit.ly/2aJDkgI @scripnews /scripintelligence

/scripintelligence /scripintelligence

2 | Scrip intelligence | 12 August 2016 © Informa UK Ltd 2016 headline news

Does CheckMate 226 Take Bristol Out Of The End Game? Emily Hayes [email protected]

Failure of Bristol-Myers Squibb’s Opdivo $20bn would derive from lung cancer. in patients with lower expression of PD-L- The patient mix for the lung cancer market 1 biomarker gives Merck & Co.’s Keytruda now is roughly 50/50 between first-line and a huge advantage in first-line lung can- second/third-line therapy, though Conover cer, and leaves market-leading Bristol to noted in an interview days before the Check- wait for combination data. Mate 026 news that it was unclear how that would change after immunotherapies start- ristol-Myers Squibb Co. has enjoyed ed being used in the first-line. He suspected a long run as the golden child of im- that patients would take a different I-O drug Bmuno-oncology but the US pharma if they fail first line I-O treatment. appears to have lost its shot at the biggest Bernstein analyst Tim Anderson expects to segment of all. see in the next five years about $1bn in lost The firm’s Aug. 5 announcement that its Opdivo sales, about a 15% drop in EPS for PD-1 inhibitor Opdivo missed the primary Bristol, and a $1bn gain in Keytruda sales – a progression-free-survival endpoint in the 6% jump in EPS for Merck. much-anticipated CheckMate 026 study in Consensus estimates put the first-line first-line lung cancer prompted a dive that NSCLC market at around $12bn, with Op- had the company closing down 15.99% and divo expected to take the lion’s share and Shutterstock: Iaroslav Neliubov Iaroslav Shutterstock: competitors up. Analysts reactions labeled it reach $12bn across all indications by 2021, a “clear disappointment and overall surprise,” also overall survival in the first-line KEYNOTE “with perhaps $7-8bn of that coming from the “worst case scenario” and “possibly the 024 study. 1L NSCLC,” Evercore ISI analyst Mark Schoene- biggest surprise of my career.” With the failure in the CheckMate 026, baum said. “All told, perhaps $4-4.5bn will Opdivo (nivolumab) so far has been a Merck seems to have a lock on that particu- be lost from the BMY model.” He sees about spectacular success. Since its first approval lar end game. It should swiftly get the first $4bn of that going to Merck, which should in metastatic melanoma in December 2014, FDA approval for first-line lung cancer, and it have the market to itself until combinations it has racked up other approvals in second- also should soon get FDA approval to lower come along in two or three years. line squamous non-small cell lung cancer, the threshold for PD-L1 expression for the Bristol has taken a beating in trading. Its non-squamous NSCLC, second-line renal cell second-line approval to just 1% or greater. shares closed down 15.99%, with Merck carcinoma and classical Hodgkin lymphoma. Merck said it has “begun to work with up 10.41% and fellow immuno-oncology Bristol reported Opdivo held an 80% share regulatory agencies to enable supplemen- competitors AstraZeneca PLC up 1.32% and of the PD-1 market and was the firm’s top- tary filing of these data to our existing Key- Roche up 1.87%. seller during the second quarter, with $840m truda labels,” the firm reiterated in a state- in sales. It was thought to have an unassail- ment on Aug. 5. What’s The Next Move? able lead over Merck & Co. Inc.’s competing Merck has already been touting that There are no immediate clues about what PD-1 inhibitor Keytruda (pembrolizumab), having the infrastructure in place for PD-L1 happened in the CheckMate 026 trial – which trailed with $314m in sales, most of testing could give it an edge on the first- though the difference in the PD-L1 expres- which derived from melanoma. line market. sion cut points used in Bristol’s trial and Mer- Lung cancer is the largest market for the Pembrolizumab and nivolumab are very ck’s Keynote 024 trial might be behind the cancer immunotherapies, and Bristol has similar and have been viewed as the same failure. While Bristol has clarified that there built its strong lead over Merck in the sec- by leading clinicians to date, but the com- did not appear to be enrollment anomalies ond-line setting in part because Keytruda panies have different development strate- or imbalances in the arms, and the chemo was hampered by a requirement for PD-L1 gies, particularly for NSCLC. Bristol has used arm performed as expected, “we will be expression testing. Bristol’s approval is for different cut-off levels for PD-L1 expression eagerly anticipating more details of the all-comers. than Merck. In second-line trials, that strat- trial data in order to tell what exactly went The biggest prize, however, is first-line egy served Bristol well, as it gained labeling wrong,” Schoenebaum said in his Aug. 5 NSCLC, where PD-L1 expression testing is for all-comers regardless of PD-L1 expres- note to investors. expected to be more the norm. sion. But in trying for the same result in the Published online 5 August 2016 That’s been Merck’s big chance to cap- first-line setting, it may have reached too far. ture market share, and it’s been pushing hard to be first to market. It seemed to be in A Look At The Market CLICK its grasp when it was the first to report data Morningstar analyst Damien Conover has es- Read full story at: from a first-line lung cancer trial; in July, it re- timated that the market for PD-1/L1 inhibi- http://bit.ly/2bb8Iuo vealed that Keytruda had improved PFS and tors will be worth $33bn in 2023, of which

scripintelligence.com 12 August 2016 | Scrip intelligence | 3 headline news

Merck, Allergan Suggested As Suitors But Biogen’s Attractiveness Questioned Biogen’s share price has risen on speculation that it is an acquisition target for Merck & Co. and Allergan Inc. But with a number of uncertainties hanging over the company, can Biogen negotiate a premium price?

Sukaina Virji [email protected]

iogen Inc.’s share price rose as much as 10% on Aug. 1, giving franchise to diversify its revenue base, a solid cash flow stream from it a market cap of $72.3bn, on media reports that the com- a partnered asset with Roche [ocrelizumab] that could be sold or se- Bpany had drawn takeover interest from Merck & Co. Inc. and curitized to finance part of the purchase, [and] an exciting late stage Allergan Inc. asset in nusinersen.” CEO George Scangos announced his resignation during Biogen decided to exercise its option on antisense candidate Biogen’s second quarter sales and earnings call on July 21, height- nusinersen following positive Phase III data from Ionis Pharmaceuti- ening uncertainty around the company’s future prospects after cals’ (formerly ISIS Pharmaceuticals) ENDEAR study. a turbulent year and raising speculation that Biogen might Leerink are also looking on the positive side of the risky Alzheimer’s be acquired. program, calling it “one of the most exciting long-term opportunities Datamonitor Healthcare has forecast Biogen’s top line to grow at in the industry” although with the caveat “albeit with considerable a modest compound annual growth rate of 1.2% out to 2025, with risk and years to pay-off.” headwinds affecting its lucrative multiple sclerosis franchise. Leerink and Baird also view the recent news of Biogen’s CEO up- Analysts, however, have mixed opinions on whether the sale of coming departure through different lenses. According to Leerink, Biogen is in the best interests of Biogen or potential acquirers. “We’ve “The unusual announcement of the imminent departure of CEO been skeptical about Biogen as a target as the base business does not George Scangos is certainly consistent with the company mount- offer substantial growth and a positive ROI (return on investment) is ing a temporary ‘For Sale’ sign to acquirers.” going to be largely dependent on the success of aducanumab in Baird analysts, however, argue that “as the CEO, Scangos would Alzheimer’s disease and would therefore be a big bet on the amyloid likely push to stay in the event of a near-term takeover.” They note hypothesis,” said Baird Equity Research analysts. that others have argued that his leaving, “coupled with announce- ment of the hemophilia spinoff, and general restructuring efforts” are ‘CEO George Scangos’ imminent an attempt to package Biogen up for sale. Credit Suisse analysts, meanwhile, have been weighing up who departure is certainly consistent with might have the most to gain by a merger with Biogen. the company mounting a temporary “From a financial perspective, Allergan would likely benefit from greater synergies in SG&A given the two companies overlap in neu- ‘For Sale’ sign to acquirers’ rology, while Merck would likely be able to generate more R&D syn- ergies given their much broader R&D infrastructure. Allergan has the lower tax rate while Biogen’s higher margins would make more of an Alzheimer’s drug aducanumab, a beta-amyloid antibody, is in impact on Merck than Allergan.” Phase III testing after Biogen moved aggressively into advanced studies following positive Phase Ib data, but betting on success in Credit Suisse would be “surprised if either company actually Alzheimer’s has historically only led to disappointment. completes this deal” but sees more strategic rationale from an Al- “We question the possibility of a premium valuation given current lergan perspective given the joint presence Allergan and Biogen Tecfidera IP (intellectual property) risk, declining MS (multiple scle- have in the neurology space. rosis) market share ahead of a substantial competitive launch and Datamonitor Healthcare’s PharmaVitae M&A Builder suggests a revenue growth gap, and the risk tied to the Alzheimer’s program,” portfolio overlap of 12.2% for Allergan and Biogen chiefly in CNS added the Baird analysts. and immunology and inflammation therapies. This compares to Biogen’s Tecfidera patent, which provides exclusivity to 2028, is 8.9% for Merck as the suitor in sales predominantly for CNS and currently being challenged. The product provides almost one third of oncology therapies. Biogen’s revenues ($3.6bn in 2015 sales). If the patent is overturned, Lead analyst Ali Al-Bazergan believes less overlap is just one reason Biogen will be reliant on a patent that expires in 2020, with potential Biogen is a better fit with Merck: a merger could make the compa- Hatch-Waxman exclusivity to 2023-2024 in the US. “Of course Merck nies a force to be reckoned with in the CNS space. “In terms of pipe- doesn’t really concern itself with IP risk and has been willing in the line, there’s an obvious overlap in the central nervous system therapy past to completely ignore binary patent decisions,” noted Baird. area, with Merck and Biogen combined boasting nine unique drugs Leerink analysts believe a potential acquisition of Biogen by Merck in development. Merck has a shared focus with Biogen in Alzheimer’s or Allergan “certainly makes sense.” disease with its lead BACE inhibitor MK-8931, which complements Biogen is attractive for several reasons, they believe. “It offers the Biogen’s adacanumab targeting amyloid-beta,” he said. perfect portfolio for an acquirer – a large, highly profitable current Published online 3 August 2016

4 | Scrip intelligence | 12 August 2016 © Informa UK Ltd 2016 headline news

A Split Won’t ‘Make Or Break’ Pfizer, CEO Read Says Jessica Merrill [email protected]

Pfizer’s chief executive assured investors Nothing has changed in regards to the recently, however, some analysts have been there is no expiration date on optionality, timeline. Read said the company is still on predicting that a Pfizer break up looks less suggesting the company could always re- track to make a decision by the end of 2016, likely, questioning the trapped value to be consider splitting up the business even if with the process being focused on deter- unlocked and given that the company’s decides against such action this year. mining if there is trapped value in the com- growth prospects have improved. bined business and if the two separate busi- Read pointed out that a break up fizer Inc. CEO Ian Read wasn’t giving nesses could operate more efficiently apart. wouldn’t improve the company’s tax situ- away any clues during the company’s The company operates two distinct ation in the near-term, something that has Psecond quarter sales and earnings businesses: Innovative Health (previously been a key initiative for the chief executive. call Aug. 2 on which way the big pharma Innovative Products), and Essential Health “A separation doesn’t, under current laws, is leaning on the issue of breaking up the (previously Established Products), cash- facilitate a speedy ability to change the domi- business, but he did remind investors there generating mature products. But Read sug- ciles of either of the companies under the sep- is a possibility that it won’t happen – and gested that even if Pfizer decides against aration rules,” he said. Both companies would that such a decision wouldn’t necessarily a break up now, that doesn’t prohibit the be held to the standard of the combined be a bad development for Pfizer. company from reconsidering in the future. company for three years post separation, “This is not a make or break decision “I don’t think that optionality necessar- he added. “I don’t see a separation as being for the company,” Read assured investors. ily has an expiration date,” Read said. “We a quick route to improving the tax situation.” “I don’t view there being a wrong answer continually look at our capital allocation, Pfizer turned in a steady second quarter here. The decision will be taken straight we continue to look at what is in the best performance. The company reported sales through the context of the best path for- interest of Pfizer, which businesses perform of $13.15bn in the second quarter, up 11% ward for shareholders.” the best in Pfizer….We will set up the infra- driven by an additional $1.14bn in revenues Investors are anxious for Pfizer to make structure to be able to look at this question coming from the acquisition of Hospira Inc. a decision on breaking up the company, at any point in the future.” Excluding Hospira, Pfizer’s sales would have something management has been consid- A decision against a split could lead to grown 1% to $12bn, the firm reported. Net ering since 2011, with a decision promised some volatility in the stock, as many investors income declined 23% to $2.02bn. to investors by the end of the year. have been advocating for a division. More Published online 2 August 2016 GSK, Google To Invest £540m In Bioelectronics JV Sukaina Virji [email protected]

GlaxoSmithKline plc is teaming up with the “Bioelectronic medicine’s vision is to employ GSK has been active in the field of bio- company formerly known as Google Life the latest advances in biology and technol- electronics since 2012. Kris Famm, head of Sciences to create bioelectronic therapeu- ogy to interpret this electrical conversation its bioelectronics R&D, has been appointed tics, and hopes to have a product ready for and to correct the irregular patterns found president of the new company. “Neuromod- market within seven years. in disease states, using miniaturized devices ulation has been around for decades and attached to individual nerves. If successful, that is part of the strength of this collabora- laxoSmithKline PLC is setting up a this approach offers the potential for a new tion” he told Scrip. new company with Verily Life Sci- therapeutic modality alongside traditional “Through the work GSK has done over the Gences LLC (formerly Google Life medicines and vaccines.” past few years we have seen a lot of potential Sciences) called Galvani Bioelectronics. Gal- in a range of diseases from metabolic, car- vani, which will be 55% owned by GSK and UK HQ diovascular, immune-inflammatory, respira- 45% by Verily, will work to develop and com- Galvani will be headquartered within GSK’s tory, and so on. The key to addressing those mercialize bioelectronic medicines. global R&D center at Stevenage in the UK, diseases successfully is to get close to the Moncef Slaoui (currently GSK’s vaccines with a second site at Verily’s facilities in South peripheral nerve and place small low power chief but the former head of R&D), will chair San Francisco. It will initially employ around electronic devices there,” Famm explained. the board of the new company. “Many of 30 researchers. The parent companies plan Published online 1 August 2016 the processes of the human body are con- to invest £540m over the next seven years trolled by electrical signals firing between in the joint venture and contribute existing CLICK the nervous system and the body’s organs, IP. The news comes a week after GSK said it Read full story at: which may become distorted in many was making £275m of new investments at http://bit.ly/2bg913d chronic diseases,” said Slaoui in a statement. three of its manufa cturing sites in the UK.

scripintelligence.com 12 August 2016 | Scrip intelligence | 5 headline news

Refocus, Optimize, Externalize: Takeda Overhauls Global R&D As it reported solid underlying growth in the fiscal first quarter, Takeda has unveiled a detailed implementation program for its stated strategic intent to refocus global R&D effort on selected disease areas, in a major overhaul that will make much wider use of external partners and affect “significant” numbers of people across the company.

Ian Haydock [email protected]

nder a sweeping new blueprint to refocus, optimize, and internally to an already selected – but as yet undisclosed – major ex- externalize its worldwide R&D activities, Takeda Pharmaceuti- ternal collaborator, Plump said. “We are in advanced discussions with Ucal Co. Ltd. is to simplify its current network of internal sites, a strategic development partner that will take on the vast majority transfer an as yet unspecified but “significant” number of employ- of development work…that will be unlike any partnership formed ees to new external partners, and fundamentally transform ways of between contract research organizations and pharma companies. working as it pursues improved focus, efficiency and appropriate ca- Through this, we will have the opportunity to transition hundreds of pability in its operations. our employees, preserving jobs.” As has already been indicated by the Japanese firm, it will reduce The alliance will be truly global, including Japan, and encompass and concentrate its R&D presence on three core therapeutic growth end-to-end trial management, but will also provide enough flexibil- areas – oncology, gastroenterology, and CNS, plus vaccines – with ity to work with other partners where necessary, he added. related activities to be geographically concentrated at its major Shonan site in Japan plus in the US, mainly in Boston but also at a Main Research Sites smaller San Diego site. This simpler structure will be complemented Under the overhaul – which Plump preferred to characterize not as by major regional centers in Deerfield, Osaka, and Zurich, and also a cost-cutting measure but rather an attempt to rebuild Takeda’s R&D smaller, leaner sites in London, Russia, China, Singapore, and Brazil. organization – there will be three main internal R&D sites globally: “Our R&D organization now is greatly fragmented” and one impor- • Shonan (Japan) – a new research park will focus on CNS and re- tant goal is simplification “to free up resources so we can do more generative medicine and also develop open innovation centers, work with partners externally,” new chief medical and scientific of- along with pharmaceutical sciences functions relocated from Juso ficer Dr. Andy Plump told a session at Takeda’s first quarter results in Japan; briefing in Tokyo. • Boston (US) – this East Coast site will act as a development center He conceded the changes will involve a reduction in Takeda’s with a focus on oncology, GI, immunomodulation, biologics, and in-house workforce and that “it will be significant. There are a lot of translational research, and be a center for external innovation; people that will be affected…but we are not ready at this point to • San Diego (US) – this West Coast site will specialize in supporting talk about a number, due to ongoing discussions with employees” technologies for GI and CNS, and support research capabilities in and other stakeholders, he said. The company noted that the figures pharmaceutical sciences. could also fluctuate “depending on the progress of implementing In addition, development activities will be consolidated in Osaka these programs and the transformation,” although Plump did note (rather than Tokyo), while pharmaceutical sciences activities at sites that key regulatory interface staff would be retained in-house. in London, Juso, Singen (Germany) and Deerfield (US) will be halted. The one-time implementation costs of the R&D overhaul will total Rationale, Site Structure around JPY75bn ($733m) but are expected to lead to recurring an- The fundamental restructuring is designed “to build a world-leading nual cost savings of around JPY18bn, which will be reinvested back R&D organization and pipeline” and sustainable, long-term future into the pipeline. growth, president and CEO Christophe Weber said in a statement. Other strategic aims are “to drive innovation, enhance partnerships, Q1 Performance and improve R&D productivity,” while increasing efficiency and put- The fundamental R&D shakeup somewhat overshadowed Takeda’s ting the right capabilities in the right areas. results for the fiscal first quarter, when underlying group revenues In general, the goal is to have “less capacity internally [for R&D] grew 9%, although the reported figure slipped 3% to JPY434.0bn, than what we need…and to use external capacity to deal with fluc- affected by currency effects and the divestment of a mature product tuations” in a flexible way on top of that, according to actual pipeline portfolio in Japan. requirements at any given time, Plump explained. Underlying core earnings jumped 40%, falling 8% reported to The narrowing of therapeutic focus also means that “we have JPY77.1bn, while reported operating profit was JPY152.9bn, more made the decision…that specialty cardiovascular…will no longer than triple the JPY49.6bn in the same period last year. Net profit at- be a strategic area for us, as we felt we didn’t have the pipeline and tributable to shareholders surged to JPY99.5bn from JPY24.6bn, in resources,” he said. Existing activities and staff in the field will be di- both cases helped by a payment for the transfer of selected older vested and transferred to an external partner, with which discussions products to the Teva Takeda Yakuhin Ltd. joint venture in Japan. are now at “an advanced stage.” From the editors of PharmAsia News. More broadly, the intention is to shift a lot of R&D work now done Published online 1 August 2016

6 | Scrip intelligence | 12 August 2016 © Informa UK Ltd 2016 business bulletin

Biogen Snaps Up Ionis’ Novo Nordisk Cuts Forecast Antisense Treatment US payer pressure resulted in a big contract loss for Novo Nordisk AS’ Shares in Carlsbad, CA-based Ionis blockbuster insulin NovoLog in the second quarter, prompting the Dan- Pharmaceuticals Inc. (formerly ISIS ish diabetes fighter to trim sales and profit forecasts for the full year. Novo Pharmaceuticals) shot up by more Nordisk signaled intensifying pricing pressure from customers in the US, than 30% to close at $38.01 on Aug. its biggest market, and warned that lower prices and escalating competi- 1 when it announced the initial data tion from biosimilars will remain a problem there. “In the US, the market from its ENDEAR study of the an- environment is becoming increasingly challenging and contract negotia- tisense candidate nusinersen plus a tions for 2017 have reflected an intensifying price competition,” chief ex- $75m license fee payment from Biogen ecutive Lars Rebien Sorensen said when updating investors on the group’s Inc., which will now assume responsi- second-quarter performance. The world’s biggest maker of insulin pre- bility for the drug’s development. Bio- sented a mixed quarterly earnings report Aug. 5 and cut its full-year sales gen’s shares also received a 4% boost. and profit forecast, burdened by the loss of a key contract for its top-selling A pre-specified interim analysis has insulin NovoLog (insulin aspart). It did not identify the contractor. The shown that babies with infantile-onset group said 2016 profit likely will climb as much as 8% – but that’s down (consistent with Type 1) spinal mus- from an earlier forecast of as much as 9% growth, while sales for the whole cular atrophy receiving nusinersen ex- of 2016 are seen rising as much as 7%, but lower than an earlier outlook perienced a significant improvement for as much as 9%. The Bagsvaerd, Denmark-based company said that after in achieving motor milestones com- completing most of its 2017 negotiations with pharmacy benefits manag- pared with those who did not, with ers for insurance coverage in the US, average prices will be “low- to mid-sin- what the companies described as an gle digit” percentage less than 2016 levels with rebates. US Health plans are acceptable safety profile. Biogen plans looking to curb diabetes drug spending. Injectable diabetes drugs, namely to start regulatory filings in the com- basal insulins and GLP-1 agonists, are the main drivers of diabetes drug ing months. spending growth there. Diabetes represents 10% of overall US drug spend- [email protected], 2 August 2016 ing on average. Both basal insulins and glucagon-like peptide-1 (GLP-1) agonists are fast-growing categories of drugs within diabetes, powered by new launches and a push toward more aggressive treatment. More treat- Lupin Buys Shionogi Brands ment options, however, also open the window for payers to implement cost management strategies. Many are moving increasingly toward closed Lupin Ltd., India’s third largest drug formularies and drug exclusions as a negotiation tactic to extract steeper firm by sales, said on Aug. 2 that its discounts from manufacturers. Japanese arm Kyowa Pharmaceutical [email protected],5 August 2016 Industry Co. Ltd. is acquiring 21 long- listed products (off-patent branded medicines) from Shionogi & Co. Ltd. for JPY15.4bn ($150m). The acquired the “clone” of the HPV vaccine and was products include sleep inducing drug now in the process of optimizing the Rhythmy, anxiolytic Resmit, psycho- How Incepta Is Shaping antigen production. It expects to start neurotic agent Novamin, antidepres- Bangladesh’s Vaccines Future testing the HPV vaccine in animals by sant Surmontil, gastritis and gastric the first quarter of 2017. “We are hope- ulcer treatment Ulgut and oral hypo- Incepta Vaccine Ltd has operationalized ful to commercially produce the HPV glycemic agent Dimelin. The transfer of an indigenous, fully integrated bulk fa- vaccine by the first quarter of 2018. It marketing and manufacturing rights cility that can manufacture both bacteri- will be a tetravalent vaccine comparable for the acquired products is effective al and viral bulk antigen independently. with Gardasil,” he said. Merck & Co. Inc. Dec. 1, 2016. The Japanese market has The facility expects to produce bulk anti- also has Gardasil 9, covering nine HPV witnessed similar deals involving long- gens for a range of vaccines that include types, five more than Gardasil which listed products products recently. One a 13-valent pneumococcal conjugate helps prevent infection caused by HPV example would be Sun Pharmaceutical vaccine and 4-valent human papilloma types 6, 11, 16 and 18. Incepta, which is that earlier this year acquired a basket virus (HPV) vaccine. Those for hepati- the first human vaccine manufacturing of 14 established prescription brands tis B, cholera and typhoid have already company in Bangladesh, has previously from Novartis AG ‘s local subsidiary for been produced and some of them are in indicated that its vaccines are generally $293m; the products had combined an- preclinical/clinical trials. Incepta’s chair available at a discount of 40-50% to the nual revenues of around $160m. and managing director Abdul Muktadir reference product. [email protected], 2 August 2016 told Scrip that the firm had prepared [email protected], 2 August 2016 scripintelligence.com 12 August 2016 | Scrip intelligence | 7 headline news

Shire Ups Synergies Forecast, Baxalta Integration On Track Sten Stovall [email protected]

Shire PLC was “firing on all cylinders” in the second-quarter, ac- Management gave a brief pipeline update during the results pre- cording to its CEO Flemming Ornskov, while simultaneously ab- sentation but said a more in depth presentation would be made in sorbing rare disease specialist Baxalta, and now expects annual New York City on Nov. 10. The combined company now has more synergies from the deal of more than $700m in three years – up than 40 programs in clinical development. from the $500m forecast ahead of the acquisition’s closing in June. Ornskov said Shire is on track to launch Xiidra (lifitegrast) in the third quarter for the treatment of both the signs and symptoms of ublin-based Shire PLC lifted its outlook for 2016 and its pre- dry eye disease after receiving recent FDA approval. The indication dicted cost saving goal for the recent $32bn purchase of US for both signs and symptoms of dry eye disease should give Xiidra Ddrug maker Baxalta Inc., as the newly formed rare disease gi- a significant advantage over the only drug currently approved for ant beat market forecasts for sales and profits in the second quarter dry eye, Allergan PLC’s Restasis (cyclosporine ophthalmic emulsion), – and its CEO predicted the strong trend would continue. which has yielded blockbuster sales despite marginal efficacy and a Shire, which acquired Baxalta in early June, reported Aug 2 that label that only cites its ability to increase tear production in patients it generated combined second-quarter revenue of $2.43bn, while with chronic dry eye. In investor presentations, Ornskov consistently non-GAAP earnings per American Depositary Receipt, the earnings has pointed to Xiidra as offering the potential to be a game-changer measure it prefers, rose 29% to $3.38bn. The London-listed company in dry eye disease and to be the fulcrum of the firm’s nascent ophthal- said it now expects annual synergies from the deal of more than mology franchise. Shire has decided to price Xiidra at around $5,000 $700m in three years, up from the $500m forecast just before the annually, putting it in direct competition with Restasis, analysts say. acquisition closed in June. Analysts say further cost optimization might still be achieved in the longer term. Datamonitor Healthcare expects that Shire will es- Shire is on track to launch Xiidra tablish additional savings by moving Baxalta’s company headquar- in 3Q for the treatment of dry ters to Ireland, where the corporate tax rate is 12.5% compared to America’s 35%. eye disease after receiving Most of Shire’s brands beat analyst estimates during the second quarter, with legacy product sales jumping 19% from the year-ago recent FDA approval quarter level. Legacy Baxalta product sales grew 12%. Shire provided full-year guidance including Baxalta for the first time, saying earnings Ornskov noted that FDA on July 29 granted Fast Track Designa- per American depositary share excluding some costs will grow to be- tion to SHP626 (volixibat) for the treatment of nonalcoholic steato- tween $12.70 and $13.10 for 2016. But the group said it has no plans hepatitis (NASH) with liver fibrosis, a serious condition with no ap- so far to start breaking out individual drug sales from the products proved therapies. acquired from Baxalta. Shire said it plans by the end of the year to resubmit the New Drug Shire’s CEO Flemming Ornskov during the trading update reiter- Application (NDA) for SHP465, a treatment of attention deficit hyper- ated his pledge to deliver double-digit compound annual top-line activity disorder following positive topline results of the SHP465 ef- growth, with more than $20bn in annual projected revenue by 2020 ficacy and safety study in adults with ADHD. and about 65% of total annual revenues generated by its rare disease Shire also used its update to announce it reached an agreement products, which offer huge growth potential. That pledge looks fea- with the U.S. Department of Justice and other authorities to end sible, analysts say, due in part to the addition of Baxalta’s core thera- investigations into marketing practices at the Dermagraft business pies Advate (octocog alfa) and FEIBA (factor eight inhibitor bypassing that Shire had sold in January 2014. The settlement, which could po- activity) for hemophilia, and Gammagard Liquid (immune globulin tentially result in a $350m settlement, is subject to further approvals, intravenous human) and HyQvia for primary immunodeficiency. the company said. Ornskov said the expanded group is innovating in a high value, Asked by reporters how Shire – which is Dublin-based, London- high growth area with huge unmet medical need. listed but US-centric – might position itself for eventual UK departure “There are over 7,000 rare diseases but only 5% of those have from the EU, Ornskov replied the group was taking a wait-and-see therapies available today. This number is increasing and that is evi- attitude. “We do between 3% and 4% of our business in the UK and denced by the increasing share of regulatory approvals they repre- we conduct clinical trials with clients based in the UK. None of that sent,” the CEO told an analysts call. “This wealth of scientific oppor- has changed. We’re in the process of merging the two organizations tunity is well-suited to Shire’s business model, where we augment – Shire and Baxalta – in the UK to a London-based location, putting internal innovation with business development such as licensing it right at the heart of the country’s life sciences center so Brexit cur- or M&A, providing us with numerous attractive opportunities to rently hasn’t had any impact on our plans.” expand our portfolio,” he added. Published online 2 August 2016

8 | Scrip intelligence | 12 August 2016 © Informa UK Ltd 2016 headline news

Mid-Sized European Companies Eager To Acquire During Growth Spurt Among Europe’s flourishing niche of mid-sized pharmaceutical companies, Italy’s Recordati and Spain’s Almirall have snapped up smaller local companies during the past six to nine months, while Switzerland’s Actelion is concentrating on executing new product launches while considering M&A.

John Davis [email protected]

he first half of 2016 saw two of Eu- acquisition of the much smaller Pro Farma start in the second or third quarter next year, rope’s mid-sized pharmaceutical was seen by Recordati as an opportunity to Eichholtz reported. Among Almirall’s inter- T companies snapping up compatri- develop its business in Switzerland, where nal projects, dimethyl fumarate (DMF) for ot companies while busily growing sales Recordati has just started to market the lipid psoriasis has been submitted for approval, and profits. They’re not just taking out as- lowering agent, Livazo (pitavastatin). expected in the second quarter of next year, sets from under the noses of Europe’s Big The international ambitions of Recordati, while ADP31415 is in Phase I. Pharma firms, they’re showing companies which recorded growing first-half 2016 rev- Almirall has also just revealed a partner- can still be built on the back of good ideas enues of €588m (+9.1%) and net income of ship with Woodcliff Lake, New Jersey-based and rigorous business development plan- €122.7m (+18.9%), are well known. It has just Patagonia Pharmaceuticals LLC to jointly ning, at relatively low price-tags. licensed Western European and Algerian, Tu- develop Patagonia’s lead product, PAT-001, a Milan, Italy-based Recordati Industria Chi- nisian and Turkish commercialization rights first-of-its-kind topical isotretinoin product, mica & Farmaceutica SPA is a case in point, to Gedeon Richter Ltd.’s novel atypical anti- for the treatment of congenital ichthyosis, having acquired Milan-based Italchimici SPA psychotic cariprazine, which was accepted that is expected to enter Phase II studies in May 2016 for €130m ($144m) for its gas- for review by the European Medicines Agen- in the fourth quarter of 2016. Almirall has troenterology and respiratory products, and cy in March 2016. The product is already mar- global marketing rights to PAT-001 in der- the Swiss company Pro Farma in the middle keted in the US by Gedeon Richter’s licensee matological indications, in exchange for an of July for CHF16m ($16.4m), in order to Allergan Inc. as Vraylar, also in March 2016. initial upfront payment of $3.5m and devel- grow its business in Switzerland. opment and regulatory milestones of $24m. But is the motivation to sell their compa- Almirall’s Growing Pipeline Almirall’s executive vice-president of nies coming from the owners rather than For Spain’s Almirall, the acquisition of Poli global commercial strategy, Alfonso Ugarte, the acquirers? “Have private European com- Holding Group (and its operating subsidiar- noted that congenital ichthyosis affects around 100,000 to 160,000 patients in the panies decided this is a good time to sell?” ies Taurus Pharma GMBH, Polichem SA and US and the same in Europe, and PAT-001 Recordati’s CFO Fritz Squindo was asked Polichem Srl) at the end of 2015 has allowed could eventually have a sales potential of during the company’s first-half 2016 earn- it to incorporate an R&D operation, a pro- more than $100m in the US alone. Congeni- ings call, held July 28. Squindo thought not, prietary formulation technology, and three tal ichthyosis is a group of chronic skin disor- saying Recordati had “not seen any major clinical-stage projects. The Spanish com- ders with persistently thick, dry, scaly or flaky changes in the M&A arena. M&A remains pany also acquired in Feb. 2016 an aesthet- skin, sometimes called “fish disease”. crowded and competitive, and we always ics company, ThermiGen LLC, for $82m that Dermatology has been earmarked as have a list of proposals,” he remarked. markets a heat-based skin surgery device. the business Almirall wants to be in, and That may be so, but another mid-sized The three Phase III products from Poli the therapeutic category now accounts European pharma, Spain’s Almirall SA, has include P3058 (a terbinafine nail lacquer, for 43% of total net sales, Ugarte reported also been on the acquisition trial, buying according to Informa Pharma Intelligence’s during the analysts’ call. Europe has be- the Lugano-Switzerland-based Poli Group Pharmaprojects database) that is being come the company’s largest sales region, Holding SRL in November 2015. It may be evaluated in onychomycosis; patients are accounting for 55% of sales, driven by the that smaller European firms are finding it in- being recruited in Europe for the Phase actinic keratosis products Solaraze (diclofe- creasingly difficult to cope with regulatory III study and patient recruitment is due to nac gel) and Actikerall (fluorouracil plus sali- and investment demands geared towards start in the US in 2017, chief scientific of- cylic acid). Almirall reported “solid” growth much larger international companies. ficer Thomas Eichholtz told the company’s in the first half of 2016, with revenues up For publicly-listed Recordati, the pur- first-half 2016 analyst’s briefing. by 5% to €428.1m and net income up by chase of Italchimici was “an opportunity to A nail psoriasis project, P3073 (calcipotriol 37% to €80.5 m, compared with the 2015 accelerate growth in Italy, and to consoli- lacquer), is in a Phase III study that has com- first half. Published online 4 August 2016 date the product portfolio,” Squindo noted, pleted EU enrolment, with US enrolment while providing some synergies on the cost expected in the first quarter of 2017, and CLICK side. Italchimici had revenues of €46m in P3074 (topical finasteride), for androgenic Read full story at: 2015 from pharmaceuticals, food supple- alopecia, which has just started enrolment http://bit.ly/2bbplVI ments and medical devices. In contrast, the in an EU study, with a US study expected to

scripintelligence.com 12 August 2016 | Scrip intelligence | 9 R&D Bites

Regeneron Emphasizes Pipeline Promise Araclon Sees Early Promise With Regeneron Pharmaceuticals Inc. ex- Alzheimer’s Vaccine ecutives emphasized the blockbuster Phase I results for Araclon Biotech’s Alzheimer’s disease vaccine, ABvac40 potential of product candidates in the – the only vaccine data presented at this year’s Alzheimer’s Association company’s late-stage research and de- International Conference – warrant further exploration of this innovative velopment pipeline on Aug. 4, while approach to the disease. The Spanish biotech, in which pharma company noting that the top-selling biologic Ey- Grifols SA is the majority shareholder, is now planning a Phase II trial for lea (aflibercept) is facing increased reim- the vaccine on the back of the positive Phase I blinded study. A total of bursement and competitive pressures. 24 patients with mild-to-moderate Alzheimer’s disease participated in the If two forthcoming US approval deci- Phase I study: 18 patients in the treatment group and six in the placebo/ sions go Regeneron Pharmaceuticals control group. Araclon said there were no significant differences with re- Inc.’s way – for the rheumatoid arthritis spect to adverse effects between participants in the group that received therapy sarilumab in October and the ABvac40 and those in the placebo group. Effectiveness of the vaccine was atopic dermatitis treatment dupilum- not assessed in the trial but the company noted that ABvac40 produced ab in the first half of 2017 – those prod- an immune response in more than 87% of patients who received the active ucts could offset a slowdown in Eylea’s product during the trial. ABvac40 is an innovative immunotherapy that sales growth. Eylea “is one of our most acts specifically against amyloid beta protein 40 using the C-terminal part important approved products and con- of the peptide. Datamonitor Healthcare analyst Maha Elsayed told Scrip, tinues to grow well globally. Eylea is “This innovative approach is warranted in Alzheimer’s disease consider- now at an annual global net sales run ing the previous safety events that have emerged with active immuniza- rate that exceeds $5bn,” president and tion against amyloid-beta.” Elsayed highlighted as an example Perrigo Co. CEO Leonard Schleifer said during Re- PLC’s AN-1792, the first active vaccine trial that was stopped in 2002 be- generon’s earning call. “This has been cause of safety issues around patients developing encephalitis. Since this driven both by the approval of Eylea in study, efforts have been made towards improving the safety of these im- new indications as well as new data that munotherapies in Alzheimer’s, she noted. have further increased the confidence [email protected], 2 August 2016 of physicians in this product.” [email protected], 4 August 2016

Seattle Genetics said it plans to file a fourth quarter from the three-month Adcetris Expands In supplemental Biologics License Appli- follow-up point in the ongoing Phase Lymphoma cation (sBLA) to expand the use of Ad- II PISCES II study; recruitment for cetris in the indication in the first half this study is already complete. On the Partners Takeda Pharmaceutical Co. of 2017 and will report the full data at basis of these data, a pivotal Phase II/ Ltd. and Seattle Genetics Inc. are push- the American Society of Hematology III study is planned in stroke disabil- ing aggressively to expand the anti- annual meeting in December. ity, applications for which are slated body-drug conjugate Adcetris (bren- [email protected], 1 August 2016 for filing in the first quarter of 2017. tuximab vedotin) in new lymphoma In 2015, ReNeuron raised more than indications. The first of three ongoing £68m to advance this and another of Phase III trials has read out positively, its pipeline programs for retinitis pig- but late-stage studies are continuing ReNeuron Presses On With mentosa, in anticipation of the cell in what are expected to be the larger Stroke Therapy Development commercial opportunities. The compa- therapy field being revivified as a R&D nies announced Aug. 1 that the Phase Further clinical testing of ReNeuron area. The full Phase I data are a boost III ALCANZA trial, evaluating Adcetris Group PLC’s cell-based therapy CTX for the field which has suffered set- in patients with CD30-expressing cu- is warranted, experts say, after two-year backs despite promising animal data. taneous T-cell lymphoma (CTCL) met follow-up data from its Phase I PISCES Given the previous negative effects for its primary endpoint, demonstrating a study published recently in The Lancet similar transplanted fetal cells in Par- highly statistically significant improve- showed that single intracerebral doses kinson’s disease patients which led to ment in the rate of objective response were associated with improved neuro- adverse events, the disappointments lasting at least four months (ORR4), a logical function with no major adverse raised concerns that stem cell therapy novel endpoint negotiated with FDA events. The next important read-out for stroke could go the same way. under a special protocol assessment. for the product should come in the [email protected], 4 August 2016

10 | Scrip intelligence | 12 August 2016 © Informa UK Ltd 2016 headline news

MedImmune Gets Creative In Diabetes With PCSK9/ GLP-1 Fusion Product AstraZeneca PLC’s MedImmune LLC will be the first drug developer to present data for a “fusion molecule” therapy combining a PCSK9 antibody with a GLP-1 peptide when a Phase I trial of its pioneering product MEDI-4166 in type 2 diabetics completes later this year. The company’s head of diabetes innovative medicines, Cristina Rondinone, explains to Scrip the thought process behind the unique combination and what to expect for further development of the novel drug in 2017. Lucie Ellis [email protected]

edImmune LLC, an AstraZeneca PLC company, will report Phase I data for its novel type 2 diabetes combination Mtherapy, MEDI-4166, the first to fuse a PCSK9 inhibiting monoclonal antibody with a GLP-1 peptide, by the end of 2016; and Cristina Rondinone, vice president and head cardiovascular and met- abolic diseases innovative medicines at MedImmune, told Scrip she expected to see the dual product in Phase II clinical trials next year. Both aspects of the fusion molecule, which is known as MEDI4166, are also being developed as separate pipeline products: the PCSK9 drug is currently in Phase II trials and the dual GLP-1/glucagon recep- tor agonist being used – MEDI-0382 – is currently at Phase I/II. “This is a very novel concept and our first question was simple, ‘Will it work?’” Rondinone said. “At MedImmune we have the capacity to do almost anything we want and I don’t know that there is anyone else trying this idea.” There are no other ongoing trials for combina- tion therapies using a PCSK9 and a GLP-1 for the treatment of type

2 diabetes listed by clinicaltrials.gov or in a number of databases as- Studio Crystal Eye Shutterstock: sessed by Scrip. trials. It launched a first time in human, Phase I, randomized, double- Both the PCSK9 (proprotein convertase subtilisin/kexin type 9) and blind study to evaluate the safety and tolerability of MEDI4166 in Oc- GLP-1 (glucagon-like peptide-1) drug classes have gained a lot of at- tober 2015 in the US – enrolling approximately 124 patients. tention in recent years, and on the back of positive data outcomes Rondinone said MedImmune’s overarching strategy for diabetes a number of products have been successful on the market for indi- R&D is to look at many possible combined mechanisms. “Our strat- cations including hypercholesterolemia and type 2 diabetes. Mean- egy is to use our protein engineers to create long-acting dual or triple while, diabetes patients have long benefited from combination for- agonists,” she said. “We are looking at all sorts of combinations in this mulations of older diabetes therapies, setting a strong precedent for area and are very excited about opportunities here. Combination two-in-one products in the area. therapies are the only way to really treat diabetes; the whole disease Diabetes may be an increasingly crowded market, but innovative and all the problems a patient has.” products with the ability to show true differentiated effects and ben- efits over older treatments have been well received by regulators and More Innovative Metabolic Research physicians and patients. Rondinone believes MedImmune’s pipeline MedImmune’s metabolic division also has an interest in cholesterol products have potential in the future market space as the drug devel- lowering drugs options outside of PCSK9s and it is currently devel- oper is seeking curative developments. “We are learning with these oping MEDI-6012, a recombinant human LCAT (rhLCAT). An enzyme newer medications for diabetes that some have effects above just in the blood, LCAT converts cholesterol to cholesteryl ester, which is glucose control, and I believe we can have better drugs still that look then sequestered in the core of the lipoprotein particle. MedImmune at the whole physiology of the disease – products that can address collected the drug via its acquisition on AlphaCore in April 2013. “The chronic renal disease and cardiovascular events in diabetic patients,” idea is to give this drug to patients after their first cardiovascular Rondinone said. “Previously, us drug researchers were going from the event in order to prevent a second CV event,” Rondinone said. “This cell, to the animal, to the man; now we are observing what is going is very interesting to me and it’s a new concept that not many re- on in man then going backwards to design our therapies so they are searchers are trying.” fit for purpose. Our most exciting goal at MedImmune is to be able Rondinone also noted that MedImmune would be seeking to work to cure diabetes.” more closely with device and technology partners in the metabolic MedImmune – which comprises nearly half of AstraZeneca’s over- space in the future. “New digital technology can help us learn more all R&D portfolio – presented preclinical data for the PCSK9/GLP-1 about our patients and our patients need to know more about what product in June 2016 during the American Diabetes Association’s an- effect the drugs they are taking are having on their body,” she said. nual meeting, but it is yet to report any data for the drug from human Published online 5 August 2016

scripintelligence.com 12 August 2016 | Scrip intelligence | 11 headline news

Allergan, Gedeon Richter Unbowed By Cariprazine MDD Phase III Trial Failure Alex Shimmings [email protected]

mine D(3)/D(2) receptor partial agonist with ISI agreed that it was not uncommon for preferential binding to D(3) receptors. depression studies to fail to separate from “It is not uncommon that clinical trials in placebo, and he was more interested in the MDD fail to show a separation from placebo update the companies gave for the prod- even with effective drugs. Both companies uct’s hoped-for label boost, particularly for remain committed to developing cariprazine negative schizophrenia symptoms. as a potential treatment option for patients In January, Allergan and Gedeon Richter suffering from this serious illness and will announced positive Phase III results for car- continue to work on a subsequent Phase III iprazine in both the prevention of schizo- trial,” the companies said in a statement. phrenia relapse and for the treatment of The double-blind MD-72 trial was evaluat- predominant negative symptoms (PNS) of ing flexible doses of cariprazine (1.5-4.5 mg) schizophrenia, and they announced they as an adjunctive treatment to antidepres- were in discussions with the FDA over the sant therapy in adults with MDD who failed submission of an efficacy supplement for to adequately respond to antidepressant each indication. For PNS, they were more monotherapy. The initial results show that specific, stating that this would come in the none of the doses provided any difference first half of next year. from the placebo arm in the study, which The companies note that PNS, such as according to the clinicaltrials.gov database social withdrawal, lack of emotional dis- planned to enrol 1,100 patients. play, is a serious unmet need for which there are no approved treatment options

Shutterstock: Lightspring Shutterstock: available, and this could prove a key differ- Unlike Vraylar, current entiator for the product. Allergan PLC and Gedeon Richter Ltd. antipsychotics have “Unlike Vraylar, current antipsychotics have hit a buffer in the development of have not shown efficacy in negative symp- their antipsychotic cariprazine in the not shown efficacy in toms,” said Raffat, and he was pleased to get additional indication of major depres- some clarity over the timings around a label sive disorder, but they plan to proceed negative symptoms expansion after it was not specified in the with a further pivotal trial, and mollified initial US label. analysts with the announcement of a The key challenge for Vraylar is to differen- filing timeline to bolster the drug’s label tiate itself on the crowded atypicals market, in schizophrenia. This contrasts with the data from a pre- and negative symptoms provides it with its vious trial, MD-75, in which flexible doses best chance. “Today, Allergan provided the op-line Phase III data for Allergan PLC of cariprazine (2-4 mg) were significantly first clear track towards how they intend and Gedeon Richter Ltd.’s atypical an- more effective than placebo in the same to pursue this labeling indication… Nega- T tipsychotic Vraylar (cariprazine) show setting. This study enrolled about 820 pa- tive symptoms remains perhaps the most it failed to separate from placebo when used tients and was conducted in both the US important indication for Vraylar in my view,” as an add-on therapy in patients with major and Europe. Raffat said. depressive disorder (MDD) in a US study. “We are disappointed with the results However, the companies are bloodied of this trial. However, we believe that our Bipolar Expansion but unbowed by the blow, and plan to box plan to move forward with another Phase The companies are also hoping to expand on with another Phase III trial in adjunctive III study in adjunctive MDD coupled with the label for Vraylar in bipolar patients, and MDD, which they hope will lead to approval our previous positive clinical trial would have started enrolment in their Phase III when added to previous positive study data provide the two studies needed for sub- clinical trial program for cariprazine as a they have garnered. Cariprazine was ap- mission,” said Allergan’s chief R&D officer, treatment for bipolar depression in the US proved in the US last September for use in David Nicholson. and Europe. This follows positive Phase IIb the treatment of manic or mixed episodes data for the drug in the treatment of bipolar of bipolar I disorder and schizophrenia Negative Symptoms depression published in November 2015 in in adults, and is awaiting EU approval for Analysts were also relatively relaxed about the Journal of American Psychiatry. schizophrenia. The drug is a potent dopa- the MDD failure. Umer Raffat at Evercore Published online 5 August 2016

12 | Scrip intelligence | 12 August 2016 © Informa UK Ltd 2016 headline news

Gonal-f 2Q Sales Allow German Merck To Up Forecast Solid US demand for Gonal-f fertility and Rebif MS drugs in the second quarter – along with commissions from its Xalkori co-promotion partnership there with Pfizer Inc. – let Merck KGaA upgrade its guidance for the full year.

Sten Stovall [email protected]

ermany’s Merck KGAA – which is previous target range of €4.1bn and €4.3bn. (follitropin alfa, r-hFSH) recombinant human trying to transform itself into a top Full-year EPS range is now €5.85 to €6.10 follicle-stimulating hormone. Goncology and immuno-oncology compared with €5.65- €6.00 previously. One of the big future hopes for Merck innovator – lifted its full-year earnings fore- Around half of the guidance upgrade is due involves its multi-billion dollar collabora- cast Aug 4 in part on the back of stable US to the strong second-quarter with the re- tion with Pfizer Inc. on the development sales for its Gonal-f fertility treatment after the mainder resulting from the sale of a minor- of immuno-oncology products, including recall of a rival product there, and for demand ity interest held by the group’s venture fund the clinical-stage PD-L1 inhibitor avelumab. for its Rebif (interferon beta-1a) treatment for that generated €30m, and on R&D. Through it, Pfizer will have access to Merck’s relapsing forms of multiple sclerosis, which Merck, based in Darmstadt, Germany, Phase II PD-L1 inhibitor, but in return Merck faces competition from oral treatments. has around 50,000 employees in around has gained wider access to the US oncology 70 countries. Over the past five years it has market – and commissions – through a co- ‘Dynamic market been rebuilding its pharma R&D organiza- promotion deal for Pfizer’s lung cancer drug tion and realigning its healthcare businesses Xalkori (crizotinib). developments gave to focus on neurology, oncology, immuno- The FDA has given avelumab break- oncology and immunology, while expand- through designation, so the group plans to our healthcare and ing its footprint in emerging markets. It also complete the drug’s US filing submission in life science businesses plans to bolster its biopharma R&D activities the early part of the second half of 2016. in Britain – despite Brexit – on grounds the Merck – which hasn’t launched a new additional tailwinds’

The company said its priorities going for- ward are now boosting its pharma pipeline, further integration of chemicals and biologi- cals maker Sigma-Aldrich, which it acquired recently for $17bn, and reducing its new fi- nancial debt which stood at €12.5bn at the end of June and only slightly lower than the €12.7bn recorded at the end of 2015. “We again achieved everything we aimed for in the second quarter. That applies to both the Sigma-Aldrich integration and the development of new medicines,” said Stefan Oschmann, chief executive of the family-controlled conglomerate which is also the largest maker of high-tech chemi-

cals for display screens. “Strong demand for Gajus Shutterstock: our products and dynamic market develop- ments gave our healthcare and life science UK is too key and dynamic a player in the life drug in a decade – is also banking on businesses additional tailwinds. Since par- sciences sphere for it not to. cladribine tablets, the oral multiple sclero- ticularly in healthcare our performance in The company continues to reap benefits sis medicine it suspended in late-stage tri- the second quarter was so good, we have in the US for its infertility therapy Gonal-f (fol- als five years ago but then resuscitated last decided to lift our forecast for the full year,” litropin injection) for follicle stimulation after September after having evaluated new data he told an analysts call. the loss of a competitor, Ferring Pharmaceu- and done additional analyses of the prod- Merck therefore now expects group net ticals Inc. , in the recombinant follicle-stimu- uct’s benefit-risk profile. The company at sales to rise this year to between €14.9bn lating hormone (rFSH) market. Analysts think the end of June submitted an application and €15.1bn from the previously forecast this benefit will flow into the second half for marketing approval with the European €14.8bn to €15.0bn, and raised its outlook of the year. But Gonal-f is seeing significant Medicines Agency for cladribine and hopes for 2016 EBITDA before special items to competition in certain EU markets from Teva to get EU approval by the middle of 2017. between €4.25bn and €4.4bn, up from a Pharmaceutical Industries Ltd.’s rival Ovaleap Published online 4 August 2016

scripintelligence.com 12 August 2016 | Scrip intelligence | 13 headline news

How To Handle Off-Label Promotion: A Guide From PhRMA And BIO Industry communication principles offer best practices for combating contrary evidence, refuting third-party comparative effectiveness analyses and sharing real-world evidence addressing health outcomes and costs. derrick gingery [email protected] Donna young [email protected]

ff-label promotion has always don’t expect companies to change their op- study designs, and the data should be clearly been one of the mine fields of mar- erations or change their compliance rules communicated in a way that’s appropriate Oketing, and with the shift toward based on the principles. “This is really meant for the intended audience, Francer said. more real-world and health economic data to inform the greater discussion right now,” While the FDA-approved labeling is “go- aimed at both prescribers and payers, two Jeff Francer, vice president and senior coun- ing to be and will remain the most authori- leading industry organizations have gotten sel at PhRMA, told Scrip. tative data about an approved drug,” he ar- together to offer a guide to best practices. PhRMA and BIO seem to have adopted gued “there’s an incredible proliferation of The Principles on Responsible Sharing of some of the same approaches FDA used for high-quality information that is not going to Truthful and Non-Misleading Information its social media strategy for their off-label be reflected in the labeling.” About Medicines with Health Care Profession- principles. In several of the practical scenarios als and Payers, released by the Pharmaceuti- offered alongside the principles, companies Impatient Payers cal Research and Manufacturers of America are encouraged to give balanced accounts of One of the most critical situations involves and Biotechnology Innovation Organization the information, but were also encouraged discussions between sponsors and payers. July 27, are intended to prod the FDA to up- to “refer the health care professionals to a Manufacturers increasingly find themselves date its regulations on the subject. website for more comprehensive informa- in situations where payers want information The agency is in the process of writing tion.” FDA’s proposed guidance for drug pro- about their products before they are com- guidances on using health care economic motion on social media notes that ads and mercialized, Francer explained. information for drug promotion and on com- other communication must be balanced and Indeed, payers begin to plan their cov- munications on unapproved uses – though include a link to a landing page with more erage and other related decisions 12 to 18 both have been in the works for years. comprehensive information. months before a medicine is on the US mar- Neither guidances nor the PhRMA/BIO “We are seeing a real revolution in health ket, he pointed out. And, Francer said, pay- principles are binding on companies, how- care and data and information sharing,” said ers don’t like to be surprised. ever, and the boundaries of off-label promo- Francer. “We believe that more robust infor- While companies have the ability to an- tion have largely been defined through First mation sharing between our companies swer unsolicited questions, “that requires Amendment cases. The trade groups hope and payers is critical to increasing the effi- payers or anybody else to know the right that the principles will lead to discussions ciencies of the marketplace.” But he stressed questions to ask and to ask them at the right on a safe harbor provision. that information must be “science-based time, and that doesn’t lead to the most suf- The principles are “intended to establish and based on established methodologies.” ficient and timely information,” he argued. responsible, science-based parameters Drug makers also must provide their infor- for accurate and trusted information shar- mation in the appropriate context, including Fighting Against ing,” the document states. PhRMA and BIO the limitations of statistical methods and Contrary Data The principles offer companies a way of PhRMA/BIO Information-Sharing Principles fighting comparative effectiveness studies 1. Commitment to accurate, science-based communication. conducted by pharmacy benefit manag- 2. FDA-approved labeling is primary source in sharing information with health care professionals. ers that favor another treatment over one 3. Companies should provide scientific substantiation if shared information is not contained in they market. Applying the principle that FDA-approved labeling. “additional science-based information from sources other than FDA-approved labeling 4. Science-based information from sources other than FDA-approved labeling helps health care professionals and payers make informed decisions for patients. helps health care professionals and payers make informed decisions,” if a company has 5. Communication should be tailored to the sophistication of the intended audience. data refuting the comparative effective- 6. Science-based information about alternative use of medicines can improve health care ness results, it “should be able to respond decision-making. to the PBM’s public statements about the 7. Communicating with payers about new medicines and new uses of approved medicines company’s drug with information from the facilitates quicker patient access upon approval. company’s research,” PhRMA and BIO assert. 8. Real-world evidence based on patient experience and pharmacoeconomic information can To be truthful and non-misleading, the improve understanding of health outcomes and costs. company should include the results of the 9. Commitment to sharing information published in scientific or medical journals. study for its and competitor products in its

14 | Scrip intelligence | 12 August 2016 © Informa UK Ltd 2016 headline news

response to the PBM statements, as well as mittees or other highly sophisticated audi- for generics. Both presidential candidates their study’s methodology and statistical ences. Such a presentation should include also have made dealing with escalating analysis techniques, data limitations, perti- descriptions of the ongoing studies for the drug prices a priority. nent safety results and bias risks. Oral and clinical stage products, such as a one-page written communications can include sum- description of each study, including the Informing The Discussion maries of the information and refer health designs, primary and secondary endpoints, Another scenario looks at what happens care professionals to a website with more results of the primary and secondary end- when a company with a marketed Parkin- comprehensive study information, accord- points, and statistical significance, which “do son’s disease drug conducts a post-hoc ing to the document. not make statements that any of the drugs analysis of data from its pivotal trials to The practical scenario could become has been determined to be safe or effective.” measure the effect of the medication on commonplace in the coming years, espe- pain, which was among the symptoms cially as more focus turns to comparative ef- measured as part of a composite primary fectiveness research and product sponsors endpoint, but whose individual symp- fight to retain market share. tom scores were not pre-specified as a The Institute for Clinical and Economic Re- secondary or tertiary endpoint and there view recently released a cost-effectiveness were no published studies available with review of new multiple myeloma therapies, contradictory evidence. which raised concerns from groups cau- So, PhRMA and BIO said, to communi- tioning against the possibility of restricting cate the analysis’ results to prescribers in a access to the products. ICER reviews have truthful and non-misleading manner, the been cited by PBMs in the past. manufacturer should disclose the omis- Biologic sponsors also may employ the sion of the effect of the drug on pain as strategy upon facing biosimilar competi- a pre-specified primary, secondary or ex- tion. Two of the leading PBMs, Express ploratory endpoint; the post hoc nature of Scripts Holding Co. and CVS Health Corp., Jeff Francer the analysis and its consequent failure to have already announced changes to their meet the FDA’s standard for an adequate formularies to favor biosimilars. PhRMA and BIO suggest that when com- and well-controlled study; the pre-spec- Another scenario covers how a company panies communicate top-level pipeline ified primary endpoints and the results; could handle an external study presenting information, they disclose the lack of FDA the methodology for the analysis, includ- contrary evidence about a product’s efficacy. approval and the possibility that some ing whether it was designed to test a pre- Say a supplemental NDA is pending for products may not be approved, as well as specified endpoint in accordance with a a new indication in children following ap- any “material safety risks” that have been pre-specified analysis plan and how the proval in adults and FDA delays the label found in the clinical studies to date. study controlled for confounding factors; update. During the delay, another study Interestingly, among the proposed rea- the results of the analysis, including the surfaces from independent investigators sons for reviewing pipeline information statistical significance and confidence with evidence against the product’s effi- is to allow a P&T committee time to plan intervals; the pertinent safety results; any cacy in children. for potential product costs. It references a other risks of bias not already specified In that case, for the product manufac- principle that “communicating with pay- with a retrospective data analysis; and the turer to give information about its study to ers about new medicines and new uses prescribers before FDA updates the label, it of approved medicines facilitates patient fact that the analysis was not included in should disclose key elements of the study access upon approval.” the product’s labeling and regulators did design, results of primary and secondary The principles state that drug manu- not consider it in approving the product. endpoints, safety results, regulatory status facturers should be allowed to talk to P&T Under that situation, PhRMA and BIO and other evidence necessary for a medi- committees about their pipeline not only said the firm should summarize all of those cal judgment. to allow time for them to make reimburse- disclosures in oral or written communica- PhRMA and BIO also advise that the com- ment decisions as well as “account for the tions and also could refer the health care pany indicate the limitations of its study by potential cost of the new medicine.” professional to a website for more compre- disclosing “the existence of only one ran- Should pricing information from a P&T hensive information about the study. domized, controlled trial supporting the committee presentation leak out of the “There can be many ways of sharing information” and “lack of any reference study meeting room, especially if the drug is information about medicines, and it may in the labeling.” expected to be impactful, any backlash not be feasible to provide comprehensive could be problematic for the sponsor. Sev- contextual information orally,” Francer said Presenting Pipeline eral federal institutions are highly interest- in an Aug. 4 email. “Thus, we believe that Information ed in the growing drug pricing issue, in- in different circumstances, combinations The principles also suggest how a company cluding Congress, which has jumped into of oral, written, and online communica- could present pipeline information to health the pricing fight in recent months, includ- tion may be appropriate.” plan pharmacy and therapeutics (P&T) com- ing pushing for a priority review pathway Published online 5 August 2016 scripintelligence.com 12 August 2016 | Scrip intelligence | 15 Policy & Regulation Briefs

CVS Excludes Lantus, Can Torrent Sustain Brazilian Mojo? Neupogen For 2017 Torrent Pharmaceuticals Ltd. reported a 20.6% decline in revenues to CVS Health Corp. is moving to promote INR15.45bn ($230.6m), with net profits down to INR2.92bn (-55%) for the the use of biosimilar and follow-on com- first quarter ended June, largely on account of a slump in the US business. petition to Amgen Inc’s. granulocyte- First quarter US revenues declined to INR4.34bn from INR8.88bn in the same colony stimulating factor drug Neupogen period last year. The first quarter of the previous fiscal included exceptional (filgrastim) and Sanofi’s glargine insulin revenues primarily on account of the launch of generic Abilify (aripiprazole) Lantus by excluding those drugs from cov- with limited competition in the US. Ex-aripiprazole, the business grew at “low erage in its standard national formulary double-digits.” But the sharp decline in 1Q earnings came laced with some in 2017. The standard formula covers ap- interesting commentary on one of Torrent’s key markets – Brazil – currently proximately 25 million individuals and is grappling with political and economic turmoil. Revenues from Brazil rose 21% among the formulary options CVS offers to INR1.67bn; the growth in Brazilian real is 31%. Torrent Brazil has “turned to its payer clients. Neupogen and Lan- the corner” during the first quarter in terms of underlying business growth as tus were not excluded from coverage in well as the impact of the foreign exchange fluctuations in Brazil, Torrent’s top 2016. “Biosimilar and follow-on biolog- brass said at a post results earnings call. “The authorities in Brazil allowed us ics will be included as a key component to take a 12.5% price increase in April, and Torrent, like most of the industry of our 2017 standard formulary strategy, peers, has taken all the allowable price increases,” Sanjay Gupta, Torrent’s ex- replacing higher cost drugs within the ecutive director (international business), said. Most of the firm’s competitors categories,” CVS said in announcing its in Brazil had also taken the “maximum price hike.” Gupta indicated that Tor- exclusion list Aug. 2. “This will include rent was focusing “very narrowly” on a clutch of 10 brands (within its basket of the biosimilar Zarxio, replacing Neupo- about 35 products there), each with sales greater than BRL15m and the three gen, to decrease the risk of infection in areas – CNS, cardio, and diabetes – that the company operates in were grow- patients receiving treatment for certain ing higher than the pharmaceutical market there. “As result of which, focused forms of cancer, and the follow-on prod- brand building efforts on some of the larger products and with the dedicated uct Basaglar – approved in Europe as a CNS and a dedicated cardio, diabetic field force, we’re seeing good traction in biosimilar – replacing the insulin Lantus Brazil. So I think this trend hopefully should continue in the future.” [email protected] , 1 August 2016 for treatment of diabetes.” Pharmacy ben- efit manager Express Scripts Holding Co. does not exclude Lantus or Neupogen in the current version of its 2017 formulary tor of Incepta Pharmaceuticals Ltd told exclusions list, which was released Aug. 1. Scrip. Generic versions of Harvoni (the However, the company is not ruling out a Will Generic Epclusa Shake Up fixed-dose combination of ledipasvir and change for Lantus when Basaglar enters sofosbuvir) have not been too successful the market. “We will reassess this cat- Bangladesh HCV Market? in Bangladesh, because genotype 1 and 4 egory when Basaglar becomes available,” Bangladesh’s HCV market report card is less prevalent in the country compared a spokesperson for the company said. currently reads along these lines: generic with other genotypes. Significantly, In- Basaglar was approved by FDA in De- versions of Sovaldi and Daklinza have cepta indicated that its generic version cember 2015 after Lilly reached a patent made significant gains leaving inter- of Gilead’s Epclusa is “almost ready” for settlement agreement with Sanofi. Under feron by the wayside, while generic Har- launch and the firm expects some rea- the agreement, Lilly can launch Basaglar voni has had a quiet run. But, the arrival lignment in market shares in the hepati- in the US on Dec. 15, 2016 in exchange of cut-price Epclusa generics could bring tis C segment with the product’s poten- for undisclosed royalties on sales. Lantus change, besides putting the spotlight on tial entry. Muktadir said that the price sales have been declining in the US as a the growing prowess of the South Asian of generic Epclusa had not been fixed reflection of price concessions to payers nation’s pharmaceutical sector. Industry yet but added that it would be “similar and competition, including from Sa- leaders there said that generic versions nofi’s own longer-acting insulin glargine, of Gilead Sciences Inc.’s Sovaldi (sofos- to [Incepta’s] Twinvir (sofosbuvir + le- Toujeo. CVS also excludes Toujeo from its buvir) and Bristol-Myers Squibb Co.’s dipasvir) – Taka800 or 1,000 per tablet.” standard formulary in 2017. US sales for Daklinza (daclatasvir) fared “very well” Gilead had earlier announced a whole- Lantus declined 15.7% to approximately and rendered interferon “almost obso- sale acquisition cost of $74,000 for a 12- $1bn in the second quarter, according to lete” in Bangladesh. “This is because of week course of Epclusa therapy, making Sanofi, while US sales for Toujeo totaled the high price of interferon in the local it cheaper than sofosbuvir, which had an about $119m. market compared to oral drugs,” Abdul initial pricing of $84,000 for 12 weeks. [email protected] , 3 August 2016 Muktadir, chair and managing direc- [email protected] , 5 August 2016

16 | Scrip intelligence | 12 August 2016 © Informa UK Ltd 2016 headline news Teva Advancing Two Advair Generics With Late 2017 Target Jessica merrill [email protected]

Teva will move forward an internal generic neric version of GlaxoSmithKline PLC’s compared to the second quarter of 2015 to Advair candidate and one acquired from blockbuster drug for asthma and chronic $2.3bn. US generic drug revenues declined Allergan to improve its chances of getting obstructive pulmonary disease is viewed 33% to $892m due to lower sales of aripip- an interchangeable version of the market- as a lucrative commercial opportunity be- razole (Abilify), esomeprazole (Nexium) and leading asthma drug approved by FDA. cause of the drug’s widespread use, pres- budesonide (Pulmicort) due to loss of exclu- sure from payers to reduce costs in the sivity. Profit of $1.1bn was down 11%. eva Pharmaceutical Industries Ltd. is category and high barriers to entry in the The company’s specialty drug business doubling down on its efforts to de- respiratory field that are expected to limit had a better quarter, with sales of $2.3bn up T velop an interchangeable generic the amount of generic competition. 9% in the quarter, fueled by sales of its top- Advair. The company will advance an inter- Two other generic drug companies have selling brand drug Copaxone (glatiramer) nal candidate and a second acquired with already confirmed they have filed ANDAs for and respiratory products. the acquisition of Allergan PLC’s generic generic versions of Advair in the US: Mylan drug business, Teva Global Generic Medi- NV and Hikma Pharmaceuticals PLC. Both Vigodman Pledges cines Group President and CEO Sigurdur applications have user fee dates in the first Copaxone 40mg Exclusivity Olafsson said during the company’s second half of 2017, although there is no guarantee Until 2H2018 quarter sales and earnings call Aug. 4. of a first round approval given FDA’s con- One overhang for Teva remains the exclusiv- cerns about the complicated delivery of ity for Copaxone, with some investors con- respiratory drugs. cerned about how long the company will Teva’s merger with Allergan’s generic be able to fend off generic competition to business positions the Israeli company its newer 40mg dose. Novartis AG’s Sandoz as the dominant player in the generic in- already launched a generic version of the dustry. The company provided investors original Copaxone, administered daily, in with a financial update for the combined June 2015, but Teva has been able to defend company in July, estimating net revenues against it by switching patients to the 40mg in 2019 would be $26.7bn to $27.8bn in dose, administered three times a week. 2019 and EBITDA would be $10.7bn to Now the company is facing generic $11.5bn. The firm also plans to host an in- threats to the new dose on multiple fronts. vestor meeting in September to overview Generic rivals including Mylan and Sandoz the combined business. have filed ANDAs for the 40mg version. Teva announced Aug. 3 that it would also Mylan announced the US Patent and Trade- buy Allergan’s Anda Inc., the fourth largest mark Office instituted an inter partes review distributor of generic pharmaceuticals in (IPR) proceeding against three of five pat- the US and a business Allergan previously ents protecting the 40mg version last year. said it would keep. Teva will pay $500m to CEO Erez Vigodman insisted during the

Shutterstock: solar22 Shutterstock: buy Anda, gaining three distribution centers conference call that the 40mg version of Co- The financial update fell just days after with a total of 650 employees. paxone will be safe until the second half of the Federal Trade Commission cleared Te- Anda came to Allergan through legacy 2018 because any generic launch prior to a va’s $40.5bn acquisition of Allergan’s generic Actavis, like the generic drug business, and final non-appealable court ruling on all five drug business July 27 and 48 hours after the Olafsson, who previously worked at Actavis, patents would be at-risk. closing of the deal Aug. 2. knows both businesses well. “It really gives The company expects a decision on the “Our intention is to continue with both us an opportunity to service our customers IPR proceedings by Aug. 25. IPR decisions programs so we have a better chance of better, not only on the generics side but also can be appealed by either side to the fed- introducing a generic interchangeable AB- in terms of our specialty business,” he said. eral circuit, Vigodman noted, a process that rated Advair to the market,” Olafsson said. Anda provides access to 60,000 pharma- should take about a year. Neither program has completed Phase III cies, Olafsson said, but is much smaller than Teva has also filed a patent infringement testing yet, he added. Teva is aiming to be the top three drug distributors in the US and lawsuit against several generic drug manu- in a position to file an abbreviated new drug has a reputation for delivering a high level facturers in Delaware district court, with application (ANDA) for a fluticasone/salme- of service. proceedings expected to begin in Septem- terol drug in late 2017 or early 2018, he said. Teva reported lower generic drug rev- ber, Vigodman said. The launch of an interchangeable ge- enues in the second quarter, down 7% Published online 4 August 2016 scripintelligence.com 12 August 2016 | Scrip intelligence | 17 deal watch

Roche Aborts But Regeneron, Amgen and Pfizer Sign Up sukaina virji [email protected]

Deal activity over the past seven days sees According to Regeneron, its collaboration a clinical and several pre-clinical assets that Roche knock back Inovio a second time, with Adicet is intended to generate multiple complement its rare disease portfolio, an Regeneron plan for its future via an alli- clinical product candidates for various he- advanced recombinant Adeno-Associated ance with Adicet Bio, Amgen supplement matological and solid tumor cancers. Under Virus (rAAV) vector design and production its preclinical pipeline with a candidate their agreement, Adicet will receive a $25m technology, and a fully functional Phase I/ from Advaxis, and Pfizer shore up its gene upfront payment, as well as research fund- II gene therapy manufacturing facility that therapy ambitions with an acquisition. ing over the next five years. Bamboo acquired from the University of North Carolina earlier this year. elow is a roundup of some of the most Amgen Unlocks Runway noteworthy transactions that occurred For Advaxis Jazz And Pfenex Team Up Bbetween July 31 and August 5. Amgen Inc. has lowered stress levels at Ad- Pfenex Inc. has granted Jazz Pharmaceuti- vaxis Inc. by signing a global agreement for cals PLC worldwide rights to develop and Roche Knocks Inovio, Again the development and commercialization commercialize multiple early stage hema- Roche has decided to break off its deal with of the small biotech’s preclinical cancer im- tology product candidates. The agreement Inovio Pharmaceuticals Inc. for the develop- munotherapy ADXS-NEO that sees it make a also includes an option for Jazz Pharmaceu- ment of hepatitis B DNA immunotherapy $40m upfront payment and purchase $25m ticals to negotiate a license for a recombi- INO-1800, which is in Phase I testing. of Advaxis stock. nant pegaspargase product candidate with The financial support from Amgen “puts Inovio’s president and CEO Joseph Kim Pfenex. Under the agreement, Pfenex will put Roche’s move down to a “strategic de- Advaxis on very solid footing to continue receive upfront and option payments total- cision in the area of hepatitis B.” The news to aggressively advance lead product ing $15m and potential milestones of up comes less than two years after Roche’s candidate axalimogene filolisbac, also to $166m and royalties. Both parties will be “surprise” decision to return rights to the known as AXAL,” said Advaxis CEO Daniel contributing to development efforts. prostate cancer immunotherapy INO-5150. O’Connor on a conference call accompa- Both products were licensed by Roche in nying the announcement. Janssen Breaks It Off 2013 for a $10m signing fee, with potential Advaxis has had a turbulent time with With Carna milestone payments to Inovio of $412.5m. AXAL, which is in Phase III testing. It had brief- Just nine months after teaming up, Janssen Inovio plans to continue development ly been the subject of an FDA clinical hold Biotech Inc. (a J&J subsidiary) has called off of INO-1800 independently. A Phase I trial last year. The hold was lifted in December. its deal with Japanese biotech Carna Biosci- is currently enrolling patients in 30 sites Advaxis will lead the clinical development ences Inc. covering a small molecule kinase in the US and Asia-Pacific. Inovio hopes to of ADXS-NEO through proof-of-concept, inhibitor program. Details are sketchy on complete enrollment in the first half of 2017 retain manufacturing responsibilities, and what went wrong, but Carna is attributing with results due in the second half. receive potential milestone payments of up to $475m plus royalties. it to discontinuation on the part of Janssen Regeneron Looks To The Future owing to “strategic reasons.” However, “this Regeneron Pharmaceuticals Inc. has en- Pfizer Expands Gene Therapy program is considered promising,” said Car- tered a collaboration and licensing agree- Presence na, and it intends to continue developing it. ment with “off-the-shelf” cell therapies de- Pfizer Inc. has expanded its commitment to veloper Adicet Bio Inc. gene therapy with the acquisition of Bam- Mayne Closes Teva/Allergan Adicet was founded by OrbiMed and Aya boo Therapeutics Inc. The privately held firm Divestiture Jakobovits, a venture partner at the VC firm is developing gene therapies for rare diseas- Mayne Pharma has completed its $652-mil- who was president and founding CEO of es related to neuromuscular conditions and lion transaction with Teva and Allergan, Kite Pharma Inc., a developer of autologous, those affecting the central nervous system. taking ownership of 37 approved and five or personalized, cell therapies. Adicet raised Earlier in the year Pfizer bought a 22% filed generic pharmaceutical products. The $51m in a series A round at the start of this stake in Bamboo for $43m. The latest trans- transaction is part of the largest generic year. The relative ease of manufacturing and action sees Pfizer buy the rest of the com- pharmaceutical divestiture overseen by the distributing off the shelf therapies may pose pany for $150m, with its shareholders be- Federal Trade Commission and the result of a threat to companies in the field of autolo- ing eligible for potential payments of up to Teva’s $40.5bn acquisition of Allergan’s ge- gous chimeric antigen receptor T-cell (CAR- $495m contingent upon certain milestones. neric drug business, which closed last week. T) therapies, including Kite and its competi- The deal significantly expands Pfizer’s pres- Mayne Pharma secured the greatest num- tors Juno Therapeutics Inc. and Novartis AG. ence in gene therapy by providing it with ber of products of the 11 buyers.

18 | Scrip intelligence | 12 August 2016 © Informa UK Ltd 2016 Expert View

New UK Cancer Drugs Fund Dismays Pharma, Charities The re-launch of the controversial Cancer Drugs Fund in the UK has offered another point for debate about cancer drug pricing, budgetary pressures and the cost of innovation. Pharma companies believe they will have to shoulder additional financial risks while patients will still not get full access to the medicines they need. Sten Stovall [email protected]

harma and charities in the UK expressed concerns following faster than any other European country and will benefit NHS pa- the formal launch of the revamped Cancer Drugs Fund, say- tients and companies alike,” a spokesperson said. NICE has already Ping the new entity – controlled by the National Institute For started looking at the drugs in the old CDF to see whether they Health and Clinical Excellence (NICE) – will not solve underlying can be recommended for routine funding, he added. problems of drug reimbursement which, in turn, restrict access to novel oncology therapies. Firms claim the NHS failed to listen to industry on how best to manage potential over-spending, while some patient groups believe the underlying problems of how cancer drug value is as- sessed have not been addressed, which they believe will leave people still without access to drugs available in other countries. NHS England earlier in July issued new guidelines on how can- cer drugs will be appraised and funded in the UK, including the operation of the controversial Cancer Drugs Fund (CDF), which had been established in 2011 as a separate silo fund for cancer drugs that NICE assessed as being too costly for the publicly funded National Health Service (NHS). It was closed in March after heavily overspending. Announcing the revamped fund is “open for business,” Jonathan Fielden, deputy national medical director at NHS England, on July

29 said: “Today marks the culmination of extensive work to ensure pogonici Shutterstock: the new CDF will benefit the cancer patients, taxpayers and in- dustry. The new approach developed by NHS England and NICE is faster and less rigid than before, meaning patients will be able CDF Overspend Worries Pharma to access promising new and innovative treatments much earlier.” A major sore point for the pharma sector will be how overspend- The new CDF is a “managed access” fund, with a fixed annual ing by the fund is financed. budget of £340m. Publishing of the reforms, unveiled late on July To avoid the CDF overspending – and thus being closed to po- 8, followed a 12-week consultation that ended in February. tential new entrants – a proportional rebate will be applied to all Under the new process, all new cancer drugs will be referred to pharmaceutical companies receiving any funding from the new NICE, which is independent of government, for appraisal, a pro- CDF budget in the event of an overspend. Agreement to this cess which will start much earlier than previously with the aim of mechanism will be a condition for all pharmaceutical companies publishing draft guidance prior to a drug receiving its marketing receiving funding from the CDF budget, according to NHS England. authorization and then final guidance within 90 days of market- That arrangement worries the pharma industry operating in ing authorization wherever possible. the UK. Any drugs receiving either a draft recommendation for routine “Given the fact that the old fund consistently overspent signifi- commissioning or, where uncertainty exists, a recommendation cantly on its allocated budget, and that industry already under- for use within the CDF will receive interim funding from the CDF writes the majority of expenditure on branded medicines over from the point of marketing authorization. and above agreed levels, a fairer and more equitable system of The new Cancer Drugs Fund will now have clear entry and exit financial risk must be prioritized,” said Paul Catchpole, value and criteria allowing medicines to move in and out over time, whereas access director at the Association of the British Pharmaceutical the old fund only had entry points. There is also a much needed Industry (ABPI), referring to the negotiated voluntary five-year system for getting some promising new cancer medicines to Na- Pharmaceutical Price Regulation Scheme (PPRS) currently in ef- tional Health Service patients more rapidly, while gathering evi- fect in Britain. dence about their effectiveness. David Montgomery, Pfizer UK’s oncology medical director, said All new drugs will enter the NICE appraisal process before li- that “while we’ve indicated our agreement to proceed with the censure, and products referred to NICE by government ministers new arrangements for the fund, we remain concerned that many will get draft recommendations at the time of a positive opin- cancer medicines still won’t get to patients through either NICE ion from the European Medicines Agency and final guidance will or the new CDF.” be published within 90 days of marketing authorization. “This is “The new CDF won’t work for many modern cancer medicines.

scripintelligence.com 12 August 2016 | Scrip intelligence | 19 Expert View

NHS England has not listened to concerns expressed by industry around the expenditure control mechanisms, in which compa- Astellas Dips Into nies are expected to underwrite 100% of all risk in managing the CDF budget,” Montgomery said, adding “we believe that this cre- ates uncertainty for industry and does not accurately reflect the Digital Health significant contribution that industry makes already in improving Ian Haydock [email protected] patient access to the medicines they need. Lisa Anson, country president for AstraZeneca UK and Ireland, New venture DigiTx will give Astellas a leg up in its quest to access said the fundamental issues with how NICE assesses cancer medi- novel digital health technologies, in a move unveiled as the Japa- cines remain. “Unless these are addressed, patients will continue to nese firm reported continued strong growth for top product Xtandi. face the same access challenges that led to the CDF being set up in the first place. Also, the new operating procedure for the CDF stellas Pharma Inc. is aiming to board the digital health train introduces a complex commercial process for companies to navi- through a new US investment venture it has set up with the gate, on top of discussions that have already taken place with NICE.” Amajor healthcare-focused venture capital group MPM Capital. Some patient groups are alarmed by the changes. California-based DigiTx Partners will invest in broad initiatives across “The new CDF will do next-to-nothing to solve the wider prob- the digital health area, with a “special focus on companies which cre- lems that are preventing NHS patients from accessing the best ate solutions that improve patient outcomes and provide substantial cancer drugs,” said Baroness Morgan, the chief executive of the synergy with a broader pharma business,” the companies said. charity Breast Cancer Now. The investments will concentrate on earlier stage companies but “The CDF was set up because NICE’s methodology was not will include both start-ups and those at the growth stage. Astellas in working for cancer drugs, and this new process offers little Japan declined to disclose further details of the investment split or change. With the Fund’s drug assessment now being handed amounts in DigiTx, or the total fund that the new company would back to NICE, we worry that patients in England will miss out on have available for investment. effective drugs being made available in other countries,” she said. The Japanese major and MPM already have some links through the But the NICE spokesperson threw the issue back at the drug US immuno-oncology venture Potenza Therapeutics Inc., in which makers, saying “it’s now up to those companies to show that they MPM is a founding investor and Astellas last year took out an option recognize the challenges as well as the opportunities their new to acquire as part of a development alliance. drugs present to patients and the NHS by showing the same flex- While MPM is already an investor in the digital health space through ibility on cost as they have in their recent negotiations with NHS the personal genetics and DNA analysis company 23andMe Inc., Astel- England for drugs already in the CDF.” las is taking its first decisive steps, apparently hoping through DigiTx to Anticipating that stance, AstraZeneca’s Anson said “we rec- tap into technologies that it might use in its own business. “We will ex- ognize NHS budget challenges, however it is also important to plore business opportunities…and extend our knowledge in the area,” recognize the value of novel breakthrough cancer medicines that chief strategy officer Dr. Kenji Yasukawa said in a statement. extend and improve the quality of patients’ lives.” Digital health encompasses everything from novel devices to Pfizer’s Montgomery noted that pharma “is a high-risk indus- improve drug delivery to mobile apps, and technology to improve try and it’s not as simple as, or sustainable to, continuously ask physician-patient interactions, digitize medical records, disseminate companies to drop the price of these specialist medicines. It will diagnoses, allow online booking of appointments, and to monitor impact our ability to make further medical progress if we do so.” individual health parameters. Roche UK’s general manager Richard Erwin echoed that frustra- Big pharma has been taking steps into the field for a while, and tion, adding: “now that the assessment of new cancer medicines other Japanese companies are now doing the same, with Eisai for for reimbursement has been returned to NICE, we must, as a mat- instance recently unveiling an online portal to help link dementia pa- ter of urgency, address the challenge they have in assessing the tients with carers and medical staff real clinical value of cancer treatments – which necessitated the creation of the original CDF. We are calling on government today Xtandi Dominates Q1 to review NICE’s assessment methodology to stop patients fac- News of the venture came as Astellas reported fiscal first quarter re- ing ongoing anxiety around the availability of existing and new sults dominated by the performance of prostate cancer drug Xtandi cancer medicines.” (enzalutamide; licensed from Medivation Inc). Global sales of the Breast Cancer Now’s Morgan said the pharmaceutical industry anti-androgen rose 9% to JPY64.2bn ($633.2m) in the three months, should also take responsibility and begin offering “more sensible dominated by the US, with Astellas saying it is looking to promote prices.” She said the UK government should also get more actively further penetration in the chemotherapy-naive metastatic castra- involved to find a workable balance. tion-resistant prostate cancer setting. “Absolutely nobody benefits if effective new drugs are not The drug has already been launched in around 60 countries in vari- made available on the NHS. We believe that enabling the Brit- ous indications, including more than 40 in the chemo-naive setting. ish government to negotiate on price – as happens elsewhere in Astellas is forecasting that worldwide sales for the full fiscal year will Europe – could significantly improve access for cancer patients,” rise by around 17% to JPY296bn. she said. From the editors of PharmAsia News Published online 8 August 2016 Published online 8 August 2016

20 | Scrip intelligence | 12 August 2016 © Informa UK Ltd 2016 Stockwatch

Stockwatch: The Art Of Strategic News Placement Earnings announcements from Teva and clinical trial results from Biogen, Ionis and Sage have turned out to have quite different interpretations in retrospect. Exciting news can sometimes look more like a vehicle for strategically timed stock promotion than a genuine material event. Andy Smith

eva Pharmaceutical Industries nusinersen in the phase III infantile-onset Almost immediately after the an- Ltd. recently pre-announced its spinal muscular atrophy ENDEAR study nouncement there were questions from Tsecond-quarter results along with enabled partner Biogen Inc. to announce social media commentators on why, rosy long-term financial guidance that the exercise of its $75m option to acquire when the study was designed to enrol 32 extended to the end of the decade. Te- the commercialization and development patients, only ten were enrolled on SAGE- va’s forecasts incorporated a number of rights for nusinersen. Despite no public 547 and 11 on placebo. In addition, since assumptions that included the acquisi- disclosure on the detail of the safety, effi- the drug is parenterally administered tion of Allergan PLC ‘s generics business cacy, how many patients had been treated and has limited patent protection, there with associated cost savings, and the an- before the study had been stopped or the were further doubts on the commercial nouncement resulted in about a 4% jump status of the other primary or secondary potential for SAGE-547. With such a small in Teva’s share price. The analysts from endpoints, the share prices of both compa- number of patients but data on the mean Mizuho suggested that Teva’s investors nies were propelled up about 30% and 8%, reductions from baseline for SAGE-547 were “reassured with above-consensus respectively. The analysts from Leerink as- and placebo in the primary endpoint of longer term guidance and a bullish stance signed $2bn in sales by 2022 for nusinersen Hamilton Rating Scale for Depression on the Allergan deal.” while those from Citigroup described the (HAM-D) at 60 hours, the number of pa- When Teva officially announced its sec- result as “good news comes early.” How- tients in each arm achieving remission ond-quarter report on August 4, the results ever, without a single p-value in sight I was (HAM-D <7) and the percentage remis- were “roughly in line with expectations” ac- left wondering about the real purpose of sion in each arm, a simulated dataset can cording to the analysts from JP Morgan but all the enthusiasm. be constructed that fits all Sage’s reported the US generics business was below ex- Later in that same week, press reports of averages and results in the same p-value. pectations. Increasing the US generic foot- Allergan’s and Merck & Co. Inc.’s. interest in Analysts from Cowen described Sage’s print was the raison d’être for the Allergan acquiring Biogen prompted a further 10% study, as having “very robust positive re- transaction so it was just lucky that Teva’s share price spike and I started to wonder sults” which of course they are not, while $15bn debt issue came a few days after its whether the nusinersen interim analysis Sage suggested that a Phase III study may rosy advertisement for its future and before announcement had been stage managed not be required, which of course it will be. last week’s earnings report. in order to push up the price for Biogen. In the cool light of retrospect, recent pre- Adding to Teva’s commentary on US Both the interim ENDEAR analysis and announced earnings and clinical trial results generic drug price deflation were the pre- any M&A interest would have been known seemed to have the real purpose of either announced sales and profits warning from by Biogen well before any of last week’s raising money, or helping to sell the com- Hikma Pharmaceuticals PLC as the lowered announcements. In the event, a ticker- pany involved. Is it too cynical to wonder if profitability of its US generics business re- tape parade of sell-side analyst notes flut- many announcements of this type are really sulted in a full-year guidance cut. tered down from the internet assigning intended just to result in a transaction rather With last week’s raised tempo on the take-out valuations for Biogen – that now than to disclose material events? utilization of biosimilars by companies included nusinersen – as high as $414 per The Magna Biopharma Income fund where their use will generate more profits share (compared to the $316 where they holdings include Allergan and Fresenius. than the originator molecule – pharmacy finished the week). Within 18 hours, these benefit managers such as CVS Health must have felt like the black flies in Alanis Andy Smith is chief investment officer of Corp. and dialysis clinics like Fresenius Morrisette’s Chardonnay as firstly Allergan Mann Bioinvest. Mann Bioinvest is the in- Medical Care AG – a strategic focus on US was suggested not to be interested and vestment adviser for the Magna BioPharma generic small molecules rather than bio- then Biogen itself was reported as not re- Income fund which has no position in the similars now looks less than strategically ceiving any formal expressions of interest. stocks mentioned, unless stated above. Dr optimal. No wonder Allergan retained its Smith gives an investment fund manager’s biosimilar business. SAGE Data view on life science companies. He has been With a p-value of 0.008 for the primary lead fund manager for four life science–spe- Biogen Acquisition endpoint, there appeared to be no scope cific funds, including International Biotech- Speculation for ambiguity in the announcement of nology Trust and the AXA Framlington Bio- Early access to the results of a positive in- SAGE Therapeutics Inc.’s Phase II trial re- tech Fund, and was awarded the Technology terim analysis of Ionis Pharmaceuticals Inc.’s sults for SAGE-547 in post-partum depres- Fund Manager of the year for 2007. intrathecally-administered antisense drug sion (PPD). Published online 8 August 2016 scripintelligence.com 12 August 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 29 July – 4 August 2016

Lead Company Partner Company Drug Indication Market REGULATORY APPROVAL Neurim Pharmaceuticals Circadin (melatonin) - insomnia Honduras Ltd. prolonged-release tablets SUPPLEMENTAL REGULATORY APPROVAL Merck & Co. Inc. - Keytruda (pembrolizumab) advanced non-small cell lung cancer EU Ipsen - Dysport (abobotulinumtoxinA) lower limb spasticity in children US REGULATORY FILING ACCEPTED Regeneron Sanofi sarilumab rheumatoid arthritis EU Pharmaceuticals Inc. SUPPLEMENTAL REGULATORY FILING ACCEPTED Taiho Pharmaceutical Co. Taisho Toyama Zosyn (tazobactam plus complicated skin and soft tissue infec- Japan Ltd. Pharmaceutical Co. Ltd. piperacillin) tions ORPHAN DRUG DESIGNATION Roche - Zelboraf (vemurafenib) Erdheim-Chester disease US Vicore Pharma AB - C21 idiopathic pulmonary fibrosis EU FAST-TRACK STATUS Microbion Corp. - MBN-101 diabetic foot ulcers US Vaccinex Inc. - VX15 MAb Huntington’s disease US Shire PLC - volixibat (SHP626) non-alcoholic steatohepatitis (NASH) US BREAKTHROUGH THERAPY DESIGNATION Novartis AG - ribociclib (LEE011) HR-positive HER2-negative breast cancer US MEI Pharma Inc. - pracinostat acute myeloid leukemia US COMPLETE RESPONSE LETTER RI-002 (intravenous primary humoral immunodeficiency ADMA Biologics Inc. - US immunoglobulin) disease REGULATORY FILING Sunovion Pharmaceuticals Inc. (Sumitomo Dainippon - SUN-101 (glycopyrrolate) chronic obstructive pulmonary disease US Pharma Co. Ltd.) SPECIAL PROTOCOL ASSESSMENT AGREEMENT Amarin Corp. PLC - Vascepa (eicosapentaenoate) dyslipidemia US PHASE III TRIAL INITIATION PharmaMar SA - lurbinectedin (PM01183) small cell lung cancer - DBV Technologies SA - Viaskin Peanut pediatric peanut allergy - EG-1962 (nimodipine Edge Therapeutics Inc. - subarachnoid hemorrhage - microparticles) PRODUCT LAUNCH Vanda Pharmaceuticals Inc. - Hetlioz (tasimelteon) non-24 hour sleep-wake disorder Germany PRODUCT RELAUNCH Afrezza (human insulin) MannKind Corp. - type I and 2 diabetes US inhaled powder Source: Informa Pharma Intelligence’s Biomedtracker

22 | Scrip intelligence | 12 August 2016 © Informa UK Ltd 2016 Appointments

Cambridge, Massachusetts-based Pro- sponsible for three pre-clinical research tions, regulatory affairs, quality assurance teostasis Therapeutics Inc. has named programs Chronos recently acquired from and overall manufacturing operations. James M. DeTore chief financial officer, Shire plc – these include a dopamine active Dr. Geoffrey S. Gilmartin chief develop- transporter inhibitor program in multiple Ascendis Pharma A/S, a clinical stage bi- ment officer, Dr. Marija Zecevic vice presi- sclerosis fatigue and the company’s orexin opharmaceutical company, has appointed dent of business development and Eric B. 1 antagonist program in addictive behav- Scott T. Smith senior vice president and Rabinowitz a new member of the com- iors. Both Murray and Schulz-Utermoehl chief financial officer. Smith was most re- pany’s board of directors. DeTore joins the have previously held leadership roles at cently director of the healthcare investment company from bluebird bio, Inc., where he Shire, AstraZeneca PLC and Merck & Co. banking group at Wedbush Securities, from was CFO from 2014 through 2016, leading 2012 to 2016, where he led the healthcare the company’s financings and investor re- Apellis Pharmaceuticals Inc. has ap- team and oversaw a substantial increase in lations strategies, and helping to raise over pointed Dr. Robert Kim chief medical of- revenue and transaction volume. Ascendis $720m in capital. Most recently, Gilmartin ficer. Kim will help the company optimize Pharma is developing an internal pipeline was senior medical lead for global medi- its drug development strategy as its clinical of therapeutics using its TransCon technol- cines development at AstraZeneca PLC. programs progress toward late-stage clini- ogy to address unmet medical needs in rare Zecevic, the founder and managing direc- cal testing. Most recently Kim was CMO disease indications. TransCon technology tor of consulting firm Zebra Ventures, has and head of R&D at startup Vision Medi- can be applied to a broad range of drug collaborated with Proteostasis Therapeutics cines. He is currently an associate clinical therapies, including proteins, peptides and on multiple projects since July 2014. Finally, professor of ophthalmology at the Univer- small molecules, to create “prodrugs” that Rabinowitz – who is currently vice president sity of California, San Francisco. provide predictable and sustained release of global corporate development at Perrigo of an unmodified parent drug. Company PLC – will replace Conor Walshe Intrexon Corporation has named Dr. An- as a member of Proteostasis’ board. drew J. Last chief operating officer, effec- Araim Pharmaceuticals, has appointed tive August 29, 2016. Last, who will oversee Ferdinand Breedveld, chair of its board of Chronos Therapeutics Ltd., a private bio- operations across the company’s multiple directors. Breedveld will succeed Dr. Tony tech company focused on ageing diseases, technology divisions and operating subsidi- Cerami, who has been chair of the board brain and nervous system disorders, has aries, will report to Intrexon’s president Geno since founding the company in 2006. Cera- named Drs. Fraser Murray and Timothy Germano. Most recently Last was executive mi will remain involved with Araim Pharma- Schulz-Utermoehl vice presidents of pre- vice president and COO of Affymetrix where ceuticals as chair of the scientific advisory clinical development. The pair joins Chronos he was responsible for directing five busi- committee, focusing his efforts on the sci- from Polleo Pharma, a UK biotech start-up ness units – overseeing strategic marketing, entific advancement of the company’s in- company they co-founded, and will be re- product management, R&D, clinical opera- nate repair receptor (IRR) platform. Scrip eleanor Malone @ScripEleanor ian Schofield @ScripIanS sarah weir @ScripSarah [email protected] [email protected] [email protected] Alexandra shimmings @ScripAlexS ashley yeo @ashleypyeo All stock images in this publication [email protected] [email protected] courtesy of www.shutterstock.com sukaina.virji @scripsuki lucie ellis @ScripLucie unless otherwise stated. [email protected] [email protected] anju.ghangurde @scripanjug lubna ahmed @ScripLubna Customer Services [email protected] [email protected] Tel: +44 (0)20 7017 5540 donna young @ScripDonnaDC paul Wilkinson @Paul__Wilkinson or (US) Toll Free: 1 800 997 3892 [email protected] [email protected] Email: [email protected] mandy Jackson @ScripMandy john Hodgson @ScripJohn To subscribe, visit [email protected] [email protected] scripintelligence.com joanne shorthouse @ScripJo mike ward @ScripMikeWard To advertise, contact [email protected] [email protected] [email protected] francesca bruce @ScripFrancesca peter charlish @petercharlish [email protected] [email protected] Scrip is published by Informa UK Limited. sten Stovall @stenstovall John davis @john023davis ©Informa UK Ltd 2016: All rights reserved. [email protected] [email protected] ISSN 0143 7690.

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