Pharma intelligence Pinkwww.ThePinkSheet.com SheetVol. 78 / No. 21 May 23, 2016 informa vator trade groups, individual insulin manu- FDA Biologic Transition facturers and legal experts call for a more balanced approach, suggesting that unex- pired marketing protections should carry Plan Creates ‘Dead Zone’ For over after products transition to BLA licenses or that such products should have the bene- Applications, Sponsors Fear fit of 12-year biologic exclusivity dating from original NDA approval. SUE SUTTER [email protected] These same commenters suggest FDA’s proposed approach on exclusivity would DA’s interpretation of the Biologics represent a constitutional “taking” under Price Competition and Innovation Act’s the Fifth Amendment, thereby laying the F“transition provisions” for certain protein groundwork for a legal challenge if the agen- products would create a “dead zone” or “black- cy sticks to its original plan. out” period for new applications that could last several years, industry stakeholders say. PROTESTS OVER PENDING In comments responding to an FDA draft FDA’s approach on APPLICATIONS guidance on the BPCIA’s “deemed to be a li- FDA’s draft guidance, released in March, cense” provisions, representatives from inno- exclusivity violates the marked its first public explanation for how it vator, generic and biosimilar industries say planned to implement the BPCIA’s transition the agency should allow pending NDAs and Fifth Amendment’s provisions (“BLAs More Appealing As ‘Transi- ANDAs for affected products to be reviewed Takings Clause and tion’ NDAs, ANDAs Set To Lose Exclusivity” — and approved after March 23, 2020. That is “The Pink Sheet,” March 21, 2016). the date when insulin, human growth hor- free trade agreements, The agency said it would not approve any mone and other products that traditionally application under Sec. 505 for a biological have been approved under the Food, Drug innovators said. product subject to the transition provisions and Cosmetic (FD&C) Act will be deemed that is pending or tentatively approved on to be licensed as biological products un- March 23, 2020. Such applications may be der Section 351 of the Public Health Service “This proposal, if implemented, will have a withdrawn and resubmitted under 351(a), (PHS) Act. devastating effect on current development the traditional BLA pathway, or as a bio- FDA proposes transition products that programs for many important protein prod- similar under 351(k). In addition, FDA said it have not received final approval by March ucts, including insulin, thereby impairing would remove affected biological products 23, 2020, would not be approved under the competition for lower-cost biological medi- from the “Orange Book” on the transition FD&C Act and must be resubmitted as BLAs. cines, increasing health care costs in the US date because these products would no lon- However, this approach would disrupt ongo- and, most importantly, limiting patient ger be “listed drugs.” ing reviews, significantly impact develop- access to affordable biological products,” FDA acknowledged that its interpreta- ment programs and dissuade companies Mylan NV’s comments state. tion could have a significant impact on from submitting applications under the FDA’s proposal that transition products development programs for products in af- FD&C Act long before the transition date, in- should lose marketing exclusivity also drew fected classes. It advised sponsors to evaluate dustry representatives said. fire from some industry stakeholders. Inno- CONTINUED ON PAGE 4 REIMBURSEMENT R&D EUropEAN NOTEBOOK Part B Demo Comments FLAME Shoots LABA/LAMA Combos Bayer Bids For Monsanto; Biosimilar Overwhelmingly Negative, Uniform Up To First Choice In COPD, p. 15 Uptake Still Sluggish; EMA Enters Drug In Content, p. 9 Pricing Debate, p. 11 Maximize Your Reimbursement Potential The balance of power behind the prescribing decision is changing: payers are ever more in charge. That means that insight into how payers make decisions – how they evaluate drugs, one against another – will be crucial to any successful drug launch. RxScorecard objectively, authoritatively, and systematically assesses marketed and pipeline drugs in a therapeutic indication from the payer’s point of view. Developed by senior medical and pharmacy leaders from major payers and pharmacy benefit managers, RxScorecard delivers practical and powerful insight into your drug’s reimbursement potential and how you can maximize it. Transparent, objective, and grounded in payer data, RxScorecard helps you refine your development path, future-proof your market access strategy, and achieve payer acceptance. Discover RxScorecard today. Visit https://goo.gl/mIof2t to review the selection of RxScorecards today. Interact with the data. Compare drugs on clinical, safety, and economic metrics. See the payer perspective. cover 11 23 exclusive online content inside: COVER FDA Biologic Transition Plan Creates ‘Dead Zone’ For Applications, Sponsors Fear Will Fortune Favor The Brave? Biosimilar Sponsors Need High Tolerance For Uncertainty www.thepinksheet.com/a/00160523015 REGULATORY UPDATE Regulatory framework for biosimilars is still a work in progress, 7 Aegerion Juxtapid Settlement Shows REMS Have Teeth: especially on the analytical and labeling issues that featured in Alternate Route To Enforce Off-Label? the Pink Sheet’s Drug Review Profile of Zarxio. 11 European Notebook: Bayer Bids For Monsanto; Biosimilar Uptake Still Sluggish; EMA Enters Drug Pricing Debate Expanded Access Programs Need FDA Policy Changes To Really Expand www.thepinksheet.com/a/00160523011 BIOSIMILARS Agency should issue statement that deaths occurring during 5 Insulin Makers To FDA: Clarify ‘Transition’ Impact On compassionate use will not automatically penalize a drug’s Drug/Biologic Combos development, ethicists from NYU Langone Medical Center say. GENERIC DRUGS 21 FDA’s ANDA Approvals ONLINE ONLY! NEW ProdUCTS FDA performance 25 FDA’s NDA And BLA Approvals tracker ADVISORY COMMITTEES Regularly updated information about new submissions, 26 Recent And Upcoming FDA Advisory Committee Meetings pending applications and FDA actions, online-only interactive content at your fingertips 24/7 at R&D www.pharmamedtechbi.com/tracker 15 FLAME Shoots LABA/LAMA Combos Up To First Choice In COPD 17 Can Checkpoint Inhibitors Jump-Start Glioblastoma Drug Development? join the conversation 20 What To Look Out For In Glioblastoma At ASCO REIMBURSEMENT We are tweeting, liking and sharing the latest industry news and insights from our global team of editors and 9 Part B Demo Comments Overwhelmingly Negative, analysts — join us! Uniform In Content BUSINESS & FINANCE @thepinksheet1 23 Deal Watch: Anacor Purchase Marks Pfizer’s Post-Allergan Bolt-On Strategy thepinksheet.com May 23, 2016 | Pink Sheet | 3 BIOSIMILARS CONTINUED FROM COVER FDA’s proposal “creates a in a product’s development in the face of whether planned submissions under Sec. 505 longer than expected FDA reviews, requests would allow adequate time for approval by regulatory ‘dead zone’ of a for major amendments or multiple review the transition date and suggested they may cycles,” the firm’s comments state. want to consider submitting an application as year or more between the a standalone or biosimilar BLA instead. WANTED: COMPROMISE ON Most of the public comments disagreed time no rational sponsor EXCLUSIVITY with FDA’s proposed handling of applica- would submit a 505(b)(2) In the draft guidance, FDA concluded that tions pending at the time of the transition any remaining non-orphan exclusivities – date. This approach is contrary to the BPCIA’s application or ANDA … and five-year new chemical entity, three-year clear language, which allows sponsors to Hatch-Waxman, or pediatric – associated submit applications under Sec. 505 until the the first date a biosimilar with an approved NDA subject to the tran- transition date, the comments said. sition provisions would cease to have any “FDA’s proposed policy will force spon- application could be effect on March 23, 2020. Furthermore, noth- sors who are ready to submit applications for submitted” – GPhA and ing in the BPCIA suggests Congress intended lower-cost biologics prior to March 23, 2020, to grant transition products a new 12-year to delay their submissions until after March the Biosimilars Council period of exclusivity available to biologics li- 23, 2020, thereby significantly delaying the censed as standalone BLAs, the agency said. review, approval and availability of biologi- FDA’s hardline interpretation on exclusiv- cal products that compete with expensive ity surprised some industry observers, who brand name biologics,” the Generic Pharma- pending at the transition date, commenters thought the agency would have tried to take ceutical Association (GPhA) and the Biosimi- said. “We caution that FDA’s proposal as it more of a middle-of-the-road approach. lars Council’s joint comments state. relates to sNDA submissions would slow While the GPhA, Biosimilars Council and “For example, if a sponsor is ready to down the approval of changes that may of- Mylan supported the agency’s view, innova- submit a 505(b)(2) application or ANDA for fer significant benefit to the public health tor groups said terminating existing exclu- a transitional biologic in June 2019, FDA’s (e.g., new indication, dosage form, or other sivity would be inconsistent with the BPCIA, proposed policy would provide a strong in- change that enhances patient compliance harm innovation incentives