A RARE REDO — An FDA advisory committee will hold two days of meetings this week to review applications for novel therapies disfavored by political appointees who have since left the agency.
The Cellular, Tissue and Gene Therapy Advisory Committee will review Capricor’s deramiocel to treat heart issues in Duchenne muscular dystrophy patients on Wednesday. Thursday will focus on Replimune’s twice-rejected immunotherapy for advanced melanoma.
The biologics faced headwinds last year under former FDA Commissioner Marty Makary and former Center for Biologics Evaluation and Research Director Vinay Prasad — both of whom publicly defended their work on rare-disease drugs as necessary to maintain the agency’s high bar for approval.
A tough FDA analysis: Briefing documents posted by the FDA ahead of Capricor’s advisory committee don’t appear kind to its cell therapy. But the debate will likely center on what statistical analysis should be used to evaluate the treatment and the timing of the unblinding of the underlying trial.
While the FDA said that it recognizes the limitations of existing therapies and the serious impact of DMD on patients’ lives, the briefing document states there must be convincing and substantial clinical evidence that a product is effective and the benefits must outweigh risks.
“After extensive analyses of the submitted data both in the original [Biologics License Application] and in the BLA resubmission, the FDA review team was unable to identify a subpopulation that may potentially derive benefit from deramiocel,” the briefing document states.
But Capricor on Monday said the FDA’s briefing materials relied on an older analysis that did not include a new cohort, arguing that its investigational therapy showed a statistically significant benefit on the primary endpoint — an evaluation of upper limb function in DMD patients.
“We believe Deramiocel offers a meaningful treatment option for boys and young men living with Duchenne, who continue to face a significant unmet medical need,” Capricor CEO Linda Marbán said in a news release.
Day 2: Briefing documents for Replimune’s meeting should be posted later this morning.
Both Makary and Prasad suggested last year that former top cancer regulator Richard Pazdur was responsible for rejecting its last bid for approval. But an April 10 complete response letter sent to the company and posted by the FDA was signed by a CBER employee whose identity was redacted. Replimune co-founder Philip Astley-Sparke told POLITICO in April that it was signed by Asha Das, director of the Office of Clinical Evaluation in the center’s Office of Therapeutic Products.
IT’S TUESDAY. WELCOME BACK TO PRESCRIPTION PULSE. Are you former CBER head Vinay Prasad? If so, we want to hear your thoughts on this week’s adcomm blitz.
Eye on the FDA
PEP TALK — The FDA’s Pharmacy Compounding Advisory Committee wrapped up a marathon two-day meeting Friday, recommending the agency allow six of seven peptides considered to be compounded by state-licensed pharmacies, Lauren reports.
While the votes mostly broke in Health Secretary Robert F. Kennedy Jr.’s favor, they represent the first step in a long regulatory process that’s almost sure to end up in court.
Here’s what Lauren is anticipating as the FDA works through the comments and the vote results:
What’s next: FDA staff made it clear during the meeting that the discussion and votes mark the beginning of the agency’s work to decide whether and how to make the peptides — typically promoted for wellness benefits — widely available under a legal pathway. The FDA classified the seven peptides, among others, in 2023 as substances that could pose significant safety risks, ending a gray regulatory regime by marking them as explicitly illegal to make.
Agency staff said they plan to propose a rule regarding the peptides’ status for compounding, which would be subject to more public comment before the FDA makes a final determination. There’s no deadline by which it must release a proposal, said Matt Lash, acting director of the FDA’s Office of Compounding Quality and Compliance.
Still, the FDA could in the interim decide to exercise enforcement discretion for the peptides, a move that would essentially place them back in pre-2023 regulatory limbo. While big-name health companies would likely wait for formal FDA action to make moves into the peptide space, smaller clinics could jump back into the market, though that still leaves…
The sourcing question: One of the major sticking points for FDA reviewers was the lack of clear information about what exactly peptide proponents were proposing for what’s known as the agency’s bulk drug substances list. The molecules in question — like BPC-157, often promoted for muscle repair, and semax for cognitive improvement and protection — aren’t consistently formulated or described in literature, meaning products could ultimately have different chemical structures leading to varied safety and effectiveness across patients.
And then there’s the question of where compounders would source the peptides, as they’d be required to buy their ingredients from FDA-registered facilities following good manufacturing practice guidelines (distinct from outfits making research-grade peptides that aren’t regulated for human use).
Several commenters insisted that they’ve found valid sources for the peptides, including Shawn Hodges, CEO of Revelation Pharma, a national network of compounding pharmacies.
“In light of last week’s meetings, a lot of our suppliers are telling us that they are aggressively upgrading their systems or facilities, and they are testing on their end to meet the FDA’s” manufacturing requirements, he told Lauren Monday.
Legal groundwork: Regardless of the outcome, stakeholders across the spectrum appear ready to sue the FDA if the final regulatory product doesn’t align with their preferred outcome.
Affiliates of the American Academy of Peptide Medicine suggested that the FDA improperly ignored information it submitted on the substances’ safety and efficacy. Meanwhile, the branded drug industry and consumer advocates warned that green-lighting the peptides for compounding would amount to an “end run” around the traditional FDA drug approval process.
CANCER CLINICAL TRIAL GUIDANCE — The FDA’s oncology center on Monday released three final guidance documents aimed at making it easier for more cancer patients to participate in clinical trials.
“Fewer than 5% of cancer patients currently receiving treatment are enrolled in clinical trials even though more than 70% say they are willing to participate,” the FDA said in an email. “The guidance documents address one reason for low participation — stringent and complex clinical trial eligibility criteria.”
The three documents focus on appropriate use of “washout periods and concomitant medication exclusions,” expanding trials to a wider group of patients with varying levels of ability to perform daily living activities and updated recommendations for appropriate laboratory values for trial eligibility.
The agency said the new recommendations stem from workshops with Friends of Cancer Research and the American Society of Clinical Oncology.
Pharma Moves
Michael Severino is Sarepta Therapeutics’ new CEO. He previously led Tessera Therapeutics and worked at AbbVie.
Document Drawer
The FDA’s Pediatric Advisory Committee will meet on Sept. 16 to review post-marketing safety for more than two dozen drugs and devices.
The FDA published four new case studies Monday demonstrating successful approaches by drugmakers that carried out rare disease drug development programs.
WHAT WE’RE READING
HHS is taking the slower regulatory approach to limiting radio and TV pharmaceutical ads, raising questions about how big a priority curbing the commercials is for the Trump administration, NOTUS’ Paige Winfield Cunningham reports.
An anti-abortion group is launching the next phase of its effort to curb access to the abortion drug mifepristone by invoking federal water pollution law, POLITICO’s Alice Miranda Ollstein and Ariel Wittenberg report.