FDA slammed over rare disease drug decisions
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The Food and Drug Administration's rejection of several new drugs for rare diseases has alarmed patient advocates and pharmaceutical companies, some of which are publicly accusing the agency of inconsistent standards and unrealistic regulatory requirements.
Why it matters: Experimental rare disease therapies already face complicated logistical and financial hurdles, even when the path for approval is predictable.
The big picture: Emerging new technologies have given new hope to the millions of Americans who live with rare conditions. But they're also forcing the FDA to grapple with dicey regulatory decisions, particularly when a drug is designed to treat very small patient populations.
- Critics say a series of recent rejections fly in the face of the Trump administration's stated commitment to fighting rare diseases and finding innovative new approaches.
- "Something has changed in the last few months. I think of it as a new, toxic ideology that has crept into the FDA, and it's having tragic consequences," said Tim Hunt, CEO of the Alliance for Regenerative Medicine, which advocates for cell and gene therapies.
- Hunt described the agency as having adopted a mindset of "methodological purity."
The other side: "Absolutely not the case. There's no new mindset, there's no methodological purity," said a senior FDA official in an interview.
- "We are looking for the smallest possible spark," the official added. "When we don't grant approval, it's usually because we don't even see the spark, let alone the fire, let alone the blaze."
Driving the news: UniQure, the sponsor of an investigational gene therapy for Huntington's disease, on Monday disclosed that the FDA views its existing data as insufficient, and that the agency has suggested the company perform an additional clinical trial.
- "It seems the FDA is leaning into their desire to pursue gold standard science," Leerink analysts wrote in an investor note.
- But what the agency is calling for "seems to be in direct contradiction to applying flexibility in rare diseases," the analysts added.
- The senior FDA official gave a different explanation: "We have not seen any data that persuades us that there's even a little effect."
What they're saying: "Our community has experienced a series of FDA actions on rare disease product applications that seem misaligned with recent public pledges to expand the use of regulatory flexibility in evaluating rare disease therapies," Annie Kennedy, chief mission officer of the EveryLife Foundation for Rare Diseases, wrote in testimony to a Senate committee last week.
- Kennedy said that since the beginning of 2025, the agency has issued at least 23 response letters to drug companies saying that it was declining to approve rare disease therapies.
- Several recently issued letters "include comments that indicate a hesitation to apply regulatory flexibility on issues such as the use of surrogate endpoints, natural history studies, external controls, and real-world evidence," Kennedy wrote.
Where it stands: Just last week, the FDA proposed new guidance supporting the development of individualized gene therapies that was widely praised by advocates and drug companies.
- But that juxtaposition makes the recent FDA rejections all the more rattling, some said.
- "The one thing biotech and markets don't like is uncertainty, and if you don't have certainty and clarity on what it takes to develop a drug ... then what are we basing our entire industry on?" said Devyn Smith, CEO of Arbor Biotechnologies and a board member of the Alliance for Regenerative Medicine.
Between the lines: The tension that exists between scientific rigor and giving patients access to promising therapies fast is nothing new, and decisions that have leaned toward regulatory flexibility have been criticized, too.
- But the clash is more acute when it comes to new treatments for rare diseases, which may not have patient populations large enough to realistically support normal clinical trials.
The difficulty of making such judgment calls may be compounded by the novelty of the drug candidates in question.
- "The drugs having issues are ones that are newer science, there isn't the kind of certain regulatory pathway for them," a senior pharmaceutical executive told Axios.
Zoom in: One of the drug candidates rejected in January by the FDA was a cell therapy for a rare blood cancer being developed by Atara Biotherapeutics and Pierre Fabre Pharmaceuticals.
- Adriana Herrera, Pierre Fabre's CEO, said the drug had previously been rejected due to manufacturing issues, which it then worked to resolve. The company was surprised that January's letter "outlined a lot of concerns around the clinical program itself, starting with the single arm of the trial."
- The issue with doing a placebo-controlled trial is that "survival for these patients is anywhere from weeks to months, so we know these patients would die if they're not treated," Herrera said.
- In response, the FDA official said: "In some cases where people think it's like we're raising the bar, we're not asking them to do a randomized study. We're finding issues in the dataset that anyone would take pause with."
The bottom line: "If you raise the standards for how long a trial would take, how you have to do this trial, and put in regulatory risk, I think that many would say you are really putting at risk the ability for companies to invest in this area and expect to have a return," Herrera said.
- But the FDA official said the problem is being misdiagnosed.
- "There's always this narrative, when people are disappointed — the easy thing is to say the regulator is the problem. The hard thing is to say our product is not as good," they said.
