January 29th 2016 No 3787 scripintelligence.com Bial Trial Tragedy: No Safety Clue From Similar Products It is now officially confirmed that the fatty SAFETY FIRST: Reasons behind termination acid amide hydrolase inhibitor at the center of products might not be due to safety of the Bial clinical trial disaster is BIA 10-2474, which was in Phase I development for the treatment of “neurological and psychiatric pathologies.” But there were few clues to its potential toxicity from previous products with this mechanism of action investigated, and chaowalek julaketpotichai/shutterstock.com chaowalek dropped from development. BIA 10-2474 is one of six products listed by Bial as being in its development pipeline, and one of two at the Phase I stage. Bial’s pipeline is dominated by projects for CNS conditions (epilepsy and Parkinson’s disease) plus pulmonary arterial hypertension, inflammation and respiratory. Fatty acid amide hydrolase (FAAH) is responsible for hydrolysis of endocannabinoid, anandamide (AEA), and N-acyl ethanolamines such as palmitoylethanolamine (PEA) and enzyme has two forms, and the FAAH class mentions theoretical concerns over long N-oleoylethanolamide (OEA). Inhibition of has several subclasses of covalent and non- acting inhibitors, and there is speculation that the enzyme increases levels of anandamide, covalent inhibitors, that are reversible and the Bial product is irreversible. a naturally occurring cannabinoid in humans non-reversible. Previous research by Merck As a mechanism, fatty acid amide that plays a role in the modulation of pain and & Co scientists on FAAH inhibitors published hydrolase inhibitors have historically not other neurodegenerative disorders. The FAAH last year in ACS Medicinal Chemistry Letters Turn to page 8 World-Top Scientist Busted For Stealing GSK Secrets US prosecutors have laid out yet another becoming a thief – scheming with one of includes charges of conspiracy to steal trade case where very intelligent people made her co-workers to steal trade secrets from the secrets, conspiracy to commit wire fraud, the stupid mistake of thinking they were too London-based drug and vaccine maker in a conspiracy to commit money laundering, smart to get caught. But they did. plot to market and sell the lifted information theft of trade secrets and wire fraud. In a 43-count indictment, US prosecutors through a US company and its Chinese Yu “Joyce” Xue, who was fired by GSK on in Philadelphia on Jan. 20 described how a affiliates formed with three other conspirators, Jan. 6, was a project co-leader at the firm’s GlaxoSmithKline PLC senior-level manager all of whom are scientists. research facility in Upper Merion, Pa., working went from being regarded as one of The indictment, filed by the US Attorney’s on monoclonal antibodies designed to link to the world’s top protein biochemists to a Office for the Eastern District of Pennsylvania, Turn to page 10 We are tweeting, chatting, liking and Let’s get sharing the latest industry news and insights from our global team of editors SOCIAL and analysts, join us! @scripnews /scripintelligence contents/editor’s letter wavebreakmedia/shutterstock.com Dooder/shutterstock.com Eleanor Malone, Editor, 9 13 Scrip Intelligence Two health crises, quite different in nature, 1 Bial Trial Tragedy: No Safety Clue 13 French Trial Tragedy: Janssen Halts From Similar Products FAAH Inhibitor Trial have come to prominence over the past couple of weeks. Both demand a response 1 World-Top Scientist Busted 14 R&D Bites from the global pharma industry. For Stealing GSK Secrets 15 Amgen Fails At US Patent Board The tragic outcome of the Phase I trial 3 BMS’ Opdivo Blasts Through NICE In Humira Challenge in Rennes, France, in which one volunteer lost his life and others have been seriously 4 10 Potential Approvals To Watch 16 Business Bulletin injured, has prompted much soul-searching For In 2016 17 Will Supreme Court Lift ‘IPR Pressure’ in industry and beyond. While the urgent Off Biopharma? 6 Where Will Technology Take Pharma need is to establish what went wrong in this In 2016? 18 Snowed-Out Sarepta Panel particular case, in the longer run attention Likely Delays FDA Verdict will inevitably turn to what general lessons 7 JPM: Biotech Values Dive, must be learned, and what changes should Industry Remains Optimistic 20 Expert View: JPM Roundtable: be made to avoid such events in future. Biotech Execs Expect Capital To Flow 9 An Uncertain Future For Alkermes An essential part of the drug development After Failed Trials 22 Stockwatch: Will Earnings process, Phase I trials thankfully rarely result Season Rescue The Sector? in catastrophic damage to human volunteers. 9 Policy & Regulation Briefs It is imperative that the risks of serious or 23 Pipeline Watch 11 Questions Arise About Latest lasting impact on healthy volunteers are kept MannKind Deal 24 Appointments as close to zero as possible, and the renewed calls for greater transparency around 11 Merck Versus Merck: Trademark Wars preclinical and early clinical data will have to Hot Up be given thorough consideration, not least in 12 Senate Skips Critical Measures order to help re-establish public trust in the In ‘Cures’ Phase I process. Meanwhile, the reports of brain damage 12 French Trial Tragedy: FDA Launches and microcephaly in newborns in Latin ‘FAAH’ Safety Probe America that have been attributed to maternal Zika virus infection suggest that the outbreak of the usually mild mosquito- transmitted infection that began in the region Scrip in 2015 will need to be taken more seriously Editor: [email protected] than had initially appeared necessary. 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The emerging threat to Reporter: a discussion on our LinkedIn group, for your Creative Content Reporter: [email protected] fetuses is prompting R&D-focused action in chance to interact with editor Eleanor Malone Editorial Assistant: [email protected] various quarters, with companies including Production: [email protected] and the rest of the Scrip Intelligence team. Pharma Data Editor: [email protected] GlaxoSmithKline, GeneOne Life Science and Global Content Director: [email protected] Follow us at: @scripnews Inovio Pharmaceuticals recently announcing All stock images in this publication courtesy of vaccine research plans. www.shutterstock.com unless otherwise stated. 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Ebola will, among other things, help facilitate prompt and effective interventions by research-based pharma companies. 2 January 29th 2016 @scripnews scripintelligence.com © Informa UK Ltd 2016 HEADLINE NEWS BMS’ Opdivo Blasts Through NICE Bristol-Myers Squibb’s PD-1 inhibitor Opdivo back and forths we have seen with other According to NICE, the decision to dispense (nivolumab) has won a recommendation recent appraisals,” said Paul Workman, chief with preliminary draft guidance had nothing to from NICE, the health technology appraisal executive of The Institute of Cancer Research. do with the Early Access to Medicines Scheme. institute for England and Wales, for use on the Gill Nuttall, founder of Melanoma UK was NICE was able to recommend the drug for the NHS as a monotherapy for melanoma. The also pleased with this news and highlighted full licensed indication based on the available drug went straight to the final stages of the the importance of immunotherapies, which evidence, for this reason there was no need for appraisal process and will compete against she said are changing survival expectations additional consultations, it said. Merck & Co’s own PD-1 inhibitor Keytruda in cancer. “We need to do more to bring Opdivo costs £439 per 4 ml vial and £1,097 (pembrolizumab). Meanwhile, research and patient access to these potentially life- per 10 ml vial, excluding VAT and any local patient organizations have expressed relief extending cancer medicines as quickly as procurement discounts. NICE’s appraisal that NICE has okayed another “exciting” new possible,” she said. committee decided that the incremental cost immunotherapy for cancer. Opdivo, like Keytruda, won approval from effectiveness ratio for the drug, compared On 22 January, NICE published its final the UK’s medicines regulator, the MHRA, to with BMS’ Yervoy (ipilimumab), Roche’s Zelboraf appraisal determination recommending enter the Early Access to Medicines Scheme (vemurafenib) and Novartis’ Tafinlar (dabrafenib), Opdivo in line with its licensed indications (EAMS), which aims to allow early availability would be less than £30,000 per quality adjusted as a monotherapy for treating advanced of promising new unlicensed drugs for life year gained. This meant the drug was cost- (unresectable or metastatic) melanoma in patients with a high unmet medical need.