The FDA’s recent closed-door roundtable with more than a dozen rare-disease advocacy groups hinted at a real reset after a stretch that many patients and families experienced as opaque, inconsistent, and nearly impossible to navigate.
The question now is whether that message will survive contact with actual approval decisions. Senior leaders stressed re-engagement, stronger science, broader use of patient-experience data, and renewed openness to outside input. Patient advocates answered with a blunt list of concerns: narrow labeling, slow reviews, refuse-to-file decisions, inconsistent treatment of natural-history data, and no clear path for ultra-rare conditions.
Agency leaders said many of the right things—about listening to patients, applying scientific flexibility, using advisory committees, and valuing patient-experience data. But those commitments matter only if they produce a review culture that is consistent, legible, and responsive to the realities of rare disease.
If the meeting produced a single headline, it was this: the FDA’s rare-disease problem is not only delay. It is trust.
What patient groups still need is evidence that this new openness will hold when approvals, labels, and access are actually on the line.
Under Vinay Prasad, who served in a senior FDA role during Makary’s tenure, the agency often seemed to raise its evidence demands after companies had already completed studies based on earlier feedback. For small patient populations, those late shifts could effectively kill therapies with clear clinical promise—or disrupt access to treatments already on the market.
On July 18, 2025, after reports of three deaths linked to acute liver failure in non-ambulatory patients treated with Elevidys or other Sarepta gene therapies using the same AAVrh74 vector, Prasad suspended Elevidys sales, placed clinical holds on other Sarepta gene therapies, and revoked Sarepta’s platform designation. Four years earlier, he had criticized Elevidys as a drug approved under watered-down scientific standards, alongside Sarepta’s Exondys 51 in 2016.
Public outcry less than a week later led the FDA to lift the suspension and, for a time, Prasad’s removal from the agency.
He later returned, renewed concerns about regulatory inconsistency.
Consider Replimune’s therapy for advanced melanoma patients who had exhausted other options. The FDA rejected the application twice, despite data showing that progression-free survival increased from 4.4 months on prior therapy to 30.6 months.
The issue was not that the treatment showed no benefit, but that the agency later concluded that a randomized trial was necessary.
A similar pattern emerged with tabelecleucel, a first-in-class therapy for a rare, aggressive, and often fatal post-transplant B-cell malignancy. Although the drug showed promise in a single study, the FDA declined to approve it twice because it wanted additional clinical trials.
When evidence standards shift after the fact, the damage extends far beyond a single application. Small biotech companies rarely have the resources to fund decade-long, multimillion-dollar trials for conditions affecting only a few hundred people. Once the regulatory path becomes unpredictable, investment pulls back—and the patients with the fewest options absorb the cost.
Since Makary’s departure, along with Prasad and his deputies last month, the FDA has shown signs that it may again be open to more practical ways of evaluating therapies—approaches that can save time, cut cost, and reduce the burden on seriously ill patients.
Last week, the FDA agreed to reconsider Replimune’s therapy and withdrew its earlier demand for a new, years-long study. The agency also reversed course on tabelecleucel, concluding that a single-arm study compared against real-world untreated patients could be sufficient.
Still, trust will take more than a change in tone.
First, the agency should revisit other breakthrough therapies that were turned away only after the goalposts moved.
In January 2026, for example, the FDA rejected early trial data suggesting that a one-time treatment slowed Huntington’s disease progression by 75%. Instead, the agency requested a controversial trial design in which some patients would undergo sham brain surgery as a control. Rather than expose patients to that risk, the company chose not to pursue the U.S. market and launched first in the U.K.
Likewise, the FDA blocked a promising one-time treatment for the neurological form of Hunter syndrome, a rare disease caused by a missing enzyme. Regulators rejected historical patient records as a comparator and questioned laboratory evidence suggesting the therapy was working.
The next major test for Sarepta Therapeutics’ full approval of Amondys 45 and Vyondys 53, treatments for boys with Duchenne muscular dystrophy with specific mutations, may come soon. These therapies have been available under accelerated approval since 2019. When they first reached the market, the FDA required a large placebo-controlled study with 225 children.
Parents have urged the FDA to grant full approval based on real-world evidence since the trial did not adequately measure meaningful outcomes like preserved mobility and respiratory function—crucial to patients and families. Applying a strict standard only here could delay or withdraw these therapies despite long-term patient reliance.
Second, the FDA should give earlier, clearer commitments on acceptable endpoints, comparator strategies, manufacturing expectations, and postmarket evidence requirements—especially when conventional randomized trials are infeasible or unethical.
Third, FDA leadership should create greater cross-center consistency so sponsors are not forced to navigate radically different evidentiary expectations depending on which review division they face. Science should drive regulatory decisions—not institutional variability.
Finally, the agency must recognize that delay is not a neutral act. For rare-disease patients, the risk is not only approving the wrong drug. It is losing the chance to try any treatment at all because the regulatory path became too uncertain to pursue.
The FDA now has a chance to rebuild trust. But it will do so only by applying clear, consistent standards that narrow the gap between scientific possibility and real-world access.
Peter J Pitts is President of The Center for Medicine in the Public Interest (CMPI). Robert Goldberg is CMPI’s Vice President
