REGULATORY UPDATE BUSINESS & FINANCE MANUFACTURING EMA, FDA Get Together On Drugs Lundbeck Takes A Singular View FDA Making A Generic Case For Eligible For PRIME And Breakthrough Toward Tackling Challenging CNS Continuous Manufacturing, p. 23 Designation, p. 19 Disorders, p. 5 Pharma intelligence Pinkwww.ThePinkSheet.com SheetVol. 78 / No. 18 May 2, 2016 informa tinue to work with FDA as it completes the Sarepta, FDA And The Dangers eteplirsen review and that it remains com- mitted to gaining approval for a Duchenne treatment. Of Strong Early Results Debra Miller, CEO and founder of the advocacy group CureDuchenne, said in an DERRICK GINGERY [email protected] interview with “The Pink Sheet” that she wants to make sure Duchenne patients and arepta Therapeutics Inc.’s proposed advocates remain focused on dealing with Duchenne muscular dystrophy treat- the agency’s concerns. Sment eteplirsen may have been “We just work as hard as we can to help doomed by the optimism created from its Sarepta and make sure this doesn’t happen early study results, which it turned out could again and design trials that FDA will like,” not be replicated. she said. And now the company finds itself in a pre- The committee’s decision was made diffi- carious situation as it looks for a way to gen- cult by the emotional and admittedly com- erate additional scientific data that match pelling testimony from dozens of patients, the overwhelmingly positive anecdotal evi- parents and advocates (“Patients Can’t Res- dence of efficacy. cue Sarepta’s Eteplirsen” — “The Pink Sheet” FDA made no secret of the fact that it had DAILY, April 25, 2016). serious concerns about the external control Patient groups dominated the audi- trial that Sarepta used to show the efficacy of ence at the meeting and testified about eteplirsen, which is proposed for Duchenne eteplirsen’s effect on Duchenne. One group patients that have a gene mutation amenable Sarepta credit: Photo also was able to contribute its own data as to exon 51 skipping (“Sarepta’s Additional Data Sarepta CEO Ed Kaye part of Sarepta’s presentation, a first for an Doesn’t Sway FDA On Eteplirsen” — “The Pink FDA advisory committee meeting (see re- Sheet” DAILY, April 21, 2016). the Icahn School of Medicine at Mt. Sinai in lated story, “Duchenne Group’s Presentation Is Agency officials said during an April 25 Pe- New York, worried that the result creates Milestone For Patient Involvement,” online at ripheral and Central Nervous System Drugs too much uncertainty about eteplirsen’s thepinksheet.com). Advisory Committee meeting on the product path forward. that they advised the company on several oc- “I don’t believe an external control is cus- ACCELERATED APPROVAL STILL casions, as early as June 2011, that its efficacy tomary in a study like this at all and so I can’t POSSIBLE? evidence would be difficult to interpret and say I’m in favor of that, but I’m very fearful With questions about the study results, a that a placebo-controlled trial was preferable. that we’ll leave here with some sort of stale- placebo-controlled trial may be required to Committee members agreed that the tri- mate between the FDA and [Sarepta],” said determine whether the anecdotal evidence al did not create enough evidence for an ac- Green, who supported accelerated approv- of effectiveness is accurate. celerated or full approval. The vote against al and abstained on the full approval vote. That may leave accelerated approval, accelerated approval was close, 7-6, and the Sarepta did not indicate it was consider- which Sarepta has requested, off the table. rejection of full approval included three ab- ing walking away from the drug after the Agency officials said during the meeting stentions (see box, p. 4). meeting. Interim CEO Edward Kaye said that if the product becomes available to all But Mark Green, a neurology professor at in a statement that the company will con- CONTINUED ON PAGE 4 DRUGS I BIOLOGICS I DEVICES There are 6,912 known languages in the world… Хорошее 좋은 결정 решение Good decision Jó Καλή acchā nirṇaya Boa döntés απόφαση God decisão beslutning 英明的决策 良い選択 Dobra Buena decisión Gute Entscheidung decyzja Bonne décision International expansion …that translates is a big move. Make sure to 6,912 ways to say you’re ready. Let our bilingual editors on the ground be your eyes and ears in Asia, delivering expert good decision analysis and inside scoops on the Asian biopharma and medical device landscape. We have earned your competitors’ trust as the leading, single best resource in such matters because we’re fluent in the language of pharmaceutical and device business. Sign up now for a FREE TRIAL and see what you’ve been missing! www.PharmaMedtechBI.com/try-pan-now 5 8 10 exclusive online content inside: Cover Sarepta, FDA And The Dangers Of Strong Early Results Duchenne Group’s Presentation Is Milestone For REGULATORY UPDATE Patient Involvement www.thepinksheet.com/a/ 00160502008 19 EMA, FDA Get Together On Drugs Eligible For PRIME And Breakthrough Designation Advocacy group gets portion of Sarepta’s formal presentation period to present eteplirsen patient experience data, believed 21 Putting the Patient in Labeling (And Drug Approval to be a first for an advisory committee meeting. Will it become Decisions) in ODE1 commonplace? AdvISORY COMMITTEES 26 Recent And Upcoming FDA Advisory Committee Meetings BUSINESS & FINANCE The US Trade Representative reports on which 5 Lundbeck Takes A Singular View Toward Tackling companies are on Watch Lists for providing Challenging CNS Disorders DATA inadequate protection of IP rights. See an 10 Venture Funding Trends For Biotech Largely Improved In 2015 interactive map identifying those countries at 13 Deal Watch: AbbVie, arGEN-X To Explore www.thepinksheet.com/a/ 00160502012 Immuno-Oncology According To GARP INTERNATIONAL 17 India’s Patent Policy Needs More Stakeholder Input, US Trade Office Urges join the conversation PEOPLE IN THE NEWS We are tweeting, liking and sharing the latest industry 7 New CEOs Helm Melinta, Apollo news and insights from our global team of editors and 8 Perrigo’s Papa: Bridge Over Valeant’s Troubled Waters analysts — join us! Or Shark Bait? @thepinksheet1 MANUFACTURING 23 FDA Making A Generic Case For Continuous Manufacturing thepinksheet.com May 2, 2016 | Pink Sheet | 3 ADVISORY COMMITTEES ing that the agency was open to using accel- WHY NO PLAcebo-CONTROL erated approval for eteplirsen. She said more TRIAL BEFORE? uncertainty will be tolerated and “sometimes Committee members seemed perplexed we will collectively get it wrong,” suggesting that a placebo-controlled trial was not com- the agency would be willing to put it on the pleted, stating that based on patient testi- CONTINUED FROM COVER market and pull it later if efficacy could not be mony an approval may have been much patients through accelerated approval, a con- confirmed. easier to endorse with such a study. firmatory study might be difficult to conduct. FDA has usually been fairly flexible with the “Reading the data from Sarepta, every “Any kind of product that’s approved under single secondary clinical endpoint seemed accelerated approval or any kind of approval, evidence it requires for approval of new treat- ments for rare diseases where there is an un- to be so positive and listening to the testi- the question of whether you can then do a trial monials and the experiences of the boys met need (“FDA Orphan Approval Flexibility Re- that’s placebo-controlled becomes very chal- and the families it just seems to me that had mains Steady As Pressure Increases” — “The Pink lenging, particularly in serious or life-threaten- there been a true placebo group that the Sheet,” Oct. 27, 2014). ing diseases where patients may not be want- differences would have been so striking and But the case for accelerated approval ap- ing to be on placebo,” said Office of New Drugs that the study may have even been stopped pears much tougher to make now and may Director John Jenkins. sooner,” said Nicole Gonzales, an associate mean Sarepta has to pursue a full approval. Sarepta has committed to conduct two con- professor in the University of Texas-Houston Woodcock’s flexibility argument also didn’t firmatory studies. PROMOVI, an open-label trial Medical School neurology department. comparing eteplirsen to untreated non-exon appear to play among the committee mem- “I’m trying to understand why there wasn’t 51 skipping patients, is expected to produce bers. After her comments, the committee an adequately powered placebo group.” data in two to three years. voted 7-3 against full approval with three ab- Sarepta officials argued during the meet- ESSENCE, a double-blind, placebo controlled stentions. ing that once its early data showed substan- study in Duchenne patients skipping exons 45 Of the three votes in favor of full approval, tial increases in dystrophin production and a and 53 that is testing another product with the two came from the committee’s patient rep- clinical response among eteplirsen patients, same mechanism of action as eteplirsen, is ex- resentatives, which may have been expected. a placebo-controlled trial would be extreme- pected to begin enrollment soon. While their voices were important additions ly difficult or impossible to enroll. Parents Center for Drug Evaluation and Research Di- to the committee, there was only one vote in would not be willing to risk not receiving rector Janet Woodcock said during the meet- favor from a non-Duchenne patient or parent. eteplirsen if they joined the study. Kaye, who also is the company’s chief medical officer, said the company at that Advisory Committee Votes time had limited manufacturing capabilities, which prevented a placebo control study.