The FDA is signaling change, but actual success depends on more than simply bringing in a new leader at the Center for Biologics Evaluation and Research; it requires accountability, transparency and consistent action.
The FDA’s Center for Biologics Evaluation and Research (CBER) continues to cycle through directors, and that’s created a significant trust problem for industry sponsors, patients, and advocates in the rare disease community.
When Vinay Prasad took the helm at CBER in May 2025, he arrived with aspirations for improved patient outcomes. But the only consistent deliverable was disruption, leaving rare disease patients and their families without the treatments they’ve been promised.
As a healthcare communications professional with two decades of experience in regulatory strategy, I’ve learned that the FDA’s stated intent matters far less than the real-life impact its decisions have on patients who have terminal illnesses like Duchenne muscular dystrophy, Huntington’s disease and Sanfilippo syndrome. Testimony from multiple witnesses at the U.S. Senate Special Committee on Aging’s February 26 hearing on rare disease drug development and regulatory review made the problem these patients face even clearer.
Physicians, advocates, industry representatives and patients’ families shared serious concerns about inconsistently applied approval pathways, disregarded surrogate endpoints, and late-stage reversals of negotiated trial designs. The cost of these contradictions was high: patients lost access to therapies and sponsors lost the ability to continually deliver therapeutic innovations.
Two weeks after the hearing, it was revealed that CBER director Vinay Prasad would depart the agency. FDA Commissioner Martin Makary says he will name a replacement before Prasad departs later this month. But a mere transition of leadership is not the same as the actual reform that Senators Rick Scott and Ron Johnson— as well as patient advocates—have made clear is necessary. Success will depend on the actions the FDA takes between now and when the new director is settled in.
The trust problem precedes personnel issues
The past year exposed a breakdown in the rare disease therapy development process. Industry sponsors place their time and capital in the FDA’s regulatory guidance, and they trust that the drug development pathway the agency provides will be upheld.
When guidance changes without explanation, the implication for sponsors is that agreements reached in good faith can be unilaterally reversed, and that trusting the regulatory process is a risk that comes without agency accountability.
I’ve had to write communications explaining why a therapy won’t reach patients as planned because the FDA shifted evidentiary expectations after clinical trials were underway. Those stories are difficult to tell, but they don’t have to be.
That’s the reason the investigation initiated by Johnson into the FDA’s recent complete response letters (CRL) is the most consequential development since the February Senate hearing. It addresses the sponsors’ greatest challenge: regulatory guidance amended without warning, resulting in an inability to meet FDA mandates and an eventual CRL.
Along with requesting these CRLs, Johnson is considering calling FDA Commissioner Makary to testify before the Permanent Subcommittee on Investigations, which the senator chairs. This request may serve to answer a critical question: Did sponsors developing rare disease therapies receive documented rationale as to why the FDA’s guidance changed?
The answer may alter the entire course of future rare disease therapy development.
UniQure’s story exemplifies the problem
In June 2025, the FDA and uniQure reached a written agreement stipulating that data from the company’s Phase 1/2 studies of AMT-130 would support a Biologics License Application (BLA) for its Huntington’s disease gene therapy. The study used an external control derived from natural history data, and topline data announced in September showed a statistically significant 75% slowing of disease progression three years after treatment with the gene therapy.
In November, the FDA reversed its position, indicating to uniQure that these data would not, in fact, be sufficient. A Type A meeting was held in January, and by March, the agency was insisting on a new Phase 3 trial. The agency says this new trial should be randomized, double-blind and sham surgery–controlled. Doing so requires patients with a fatal, progressive neurological disease to undergo intracranial injection or a procedure with no therapeutic benefit, potentially for years.
Johnson called the sham surgery request “bureaucratic idiocy” and raised an important, and very obvious, question: what changed, especially since Huntington’s disease has no approved treatment? Every year of additional trial time is a year of disease progression for patients who already understand what that means.
The FDA’s position changed between the June 2025 agreement and the November reversal, but no documented rationale was provided. If the FDA cannot answer that question, then no new CBER director can fix what’s broken, because they won’t know where to start.
Real progress requires rebuilding trust
In February, the FDA issued draft guidance on a new plausible-mechanism framework for individualized therapies for ultra-rare disease. The following month, the FDA approved Rocket Pharmaceuticals’ Kresladi, the first gene therapy for a rare pediatric immune disease called severe leukocyte adhesion deficiency type I, using accelerated approval supported by surrogate endpoints.
These are meaningful steps, demonstrating exactly what the Senate called upon the FDA to do: use existing protocols and to apply logical flexibility and with the right scientific expertise. Still, the new CBER director inherits a significant credibility problem. The incoming leader must rebuild trust while cooperating with an ongoing government investigation. An “onboarding and transition plan” alone won’t suffice. The new director must address four essential mandates.
First, the FDA must respond publicly to Johnson’s request for the CRLs, and the agency must share its plan for ongoing, transparent dialogue regarding review process reforms.
Second, CBER needs to provide more overall clarity for the scientific community and industry sponsors about how it will apply surrogate endpoint guidance.
Third, the FDA must establish a rare disease advisory committee and engage it regularly for appropriate review processes.
Fourth, the agency must commit to the consistent application of accelerated approval pathways when documented criteria are met.
There’s an important difference between transition and transformation. In this case, the transition of leadership is just a process, but the transformation is what’s going to advance science, improve outcomes and potentially save lives. Reform is possible as long as the agency focuses on transparency and outcomes, rather than simply the bureaucracy of the transition itself.
