Rare disease advocates and industry leaders are calling for greater consistency in the U.S. Food and Drug Administration’s (FDA) regulatory process after a year marked by mixed signals and shifting policies.
Throughout 2025, FDA Commissioner Marty Makary and Center for Biologics Evaluation and Research director Vinay Prasad have made public statements supporting improved access to rare disease treatments. The agency has approved therapies for conditions like Barth syndrome and glioma but rejected others, including investigational drugs for advanced melanoma and pyruvate dehydrogenase complex deficiency. UniQure’s gene therapy for Huntington’s disease remains in regulatory limbo following indications from the FDA that current trial data is insufficient to support approval.
Steven Grossman, policy consultant and author of the FDA Matters blog, highlighted the lack of clear standards during a recent BioSpace webinar. “We need to have a consistent policy when to say, ‘Yes, unproven, but you can have it,’ and ‘No, unproven makes enough of a difference here.’”
Mark Veich, CEO of Advancium Health Network, echoed this sentiment in an interview with BioSpace: “I think, like anything, when there’s uncertainty, people tend to shy away from working in that space, investing in that space. If there could be some standardization in this kind of rare disease space, I think everybody wins.”
John Stanford, founder & executive director of Incubate, noted the challenge: “It’s hard to balance, it’s hard to standardize” due to the wide variety of rare diseases.
Veich suggested that while one-size-fits-all rules may not work given disease diversity, standardized clinical trial requirements—such as patient enrollment numbers based on prevalence—could provide clarity. He also advocated for more consistent use of real-world data and new technologies like artificial intelligence in trials.
Debates over trial design were prominent at BIO2025 in June during a panel hosted by BioSpace. Ultragenyx CEO Emil Kakkis said: “The problem is… most things that go into Phase III have had a Phase II study and have some evidence that maybe the drug might work. Otherwise they wouldn’t invest in Phase III to begin with.”
Stanford raised ethical questions about how different rare diseases are prioritized: “I don’t think there’s consensus,” he said. “I think a lot of it comes down to personal beliefs about what helps the most people…”
The FDA’s Accelerated Approval program was designed to speed development for drugs addressing serious or life-threatening conditions but lacks clarity on what qualifies as “serious.” Grossman commented at the BioSpace event: “The system that’s being run now is kind of based on exceptionalism… Why does DMD get a little extra consideration, but maybe not ALS?”
Recent regulatory decisions highlight inconsistencies. Sarepta Therapeutics’ Duchenne muscular dystrophy treatment Vyondys 53 was approved months after initial rejection; its gene therapy Elevidys resumed shipments quickly after safety concerns arose. In contrast, BrainStorm Cell Therapeutics’ ALS candidate NurOwn remains stalled despite similar circumstances.
Amylyx Pharmaceuticals’ ALS drug Relyvrio received approval after an initial setback but was later withdrawn from markets following failed confirmatory studies—a scenario Vyondys 53 could potentially face after disappointing results last month.
Veich argued perceptions of favoritism may stem from media coverage rather than actual regulatory bias: “But I don’t know that the FDA is giving them any favoritism,” he said. “The FDA first and foremost… is just making sure that patients are safe.”
Stanford pointed out another source of perceived inequity—the Commissioner’s National Priority Voucher program launched this year—which expedites review timelines for select drugs aligned with national priorities. “We seem to be in a winners and losers moment,” Stanford said. However he cautioned against relying on subjective programs for business planning.
Richard Pazdur recently questioned whether such expedited pathways compromise patient safety or legality amid their expansion at the agency.
Uncertainty has affected companies like Replimune whose stock dropped sharply after its advanced melanoma therapy was rejected by the FDA—a situation other firms such as uniQure and Capricor Therapeutics have also experienced.
Stanford concluded: “What we also don’t want to do is move medicines that don’t work along too quickly and weaken confidence in the whole system… people are questioning the FDA more than they normally do…”
