The U.S. Senate has a plan to improve drug development for rare disease patients. The exit of controversial CBER chief Vinay Prasad will help clear the path.
Last month, the Senate convened a bipartisan hearing to identify the root cause of medications not being readily available to patients. Eight days later, Vinay Prasad resigned from his position as director of FDA’s Center for Biologics Evaluation and Research (CBER).
These may not seem related, but some industry influencers attribute the challenges sponsors have faced in bringing therapies to market to the way Prasad led CBER—especially in the rare disease space. The end of his tenure, which featured more discordance than the nation’s healthcare regulatory agency should have, means that a path has been cleared for the Senate to bring much-needed change to the rare disease treatment landscape.
As the head of CBER, Prasad could have recognized this problem and guided the agency in a different direction. He chose not to.
Now it’s incumbent on the FDA to implement the necessary reforms. The agency has become a barrier to access over the past year—a serious problem that has left patients who already have limited therapeutic options unable to access the ones that do exist.
The Senate Demanded Answers, Harsh Truths Were Revealed
At the Senate hearing, industry leaders, physicians, advocates and parents of children with rare diseases presented evidence of inconsistently applied regulatory guidelines, underutilization of available resources and patients who are paying the price for these discrepancies.
As a healthcare communications professional with two decades of experience in regulatory strategy, I’ve watched sponsors accommodate FDA requests for trial design changes and new datasets. I’ve also seen the subsequent fallout as small biotechs try to figure out how to fund new studies, while patients, families and advocates wait without answers as to why.
These obstacles are avoidable. Protocol reform is not optional, and the rare disease community is no longer asking.
Senators and witnesses described accelerated approval pathways without utilization standards. They detailed the disregard for surrogate endpoints, despite scientific validation. Industry leaders and physicians explained how reviewers apply different standards across similar cases and offer no guidance regarding their expectations.
Witnesses detailed the consequences of late-stage reversals of negotiated trial design and endpoint agreements. When those occur, development timelines stretch beyond what small gene therapy innovators can finance and far past the threshold that patients can wait for treatment. Since the start of 2025, 23 Complete Response Letters (CRL) have been issued to rare disease sponsors, and as witnesses explained, many had little to no justification.
One moment from the hearing was particularly poignant. Dr. Jeremy Schmahmann, a Mass General neurologist and Harvard Med School professor, testified that during a regulatory review meeting at which a rare disease patient spoke about their challenges, a CDER official asked in response, “Why should I listen to you?”
That’s a failure of human values. One of the country’s most essential government agencies needs leaders who not only understand rare disease science and patient needs but also implement processes with empathy.
As the head of CBER, Prasad could have recognized this problem and guided the agency in a different direction.
He chose not to.
Rare Disease Science Requires Different Standards
Rare disease trials are small because the patient population is small. Surrogate endpoints are often the only way to measure therapeutic effect in a reasonable timeframe. That’s the reality of treating diseases that may only affect a few hundred people. Regulators cannot continue to treat this fact as a failure in clinical trial design.
Congress recognized these scientific facts when it created accelerated approval pathways, authorized orphan drug incentives and passed PDUFA legislation. Flexibility was built into the regulatory framework because it was understood that highly specialized gene therapies for rare diseases cannot be evaluated by the same criteria as small-molecule drugs that treat millions of people with the same chronic condition.
Witnesses testified that at the current rate of drug development and approval, it will take 150 years to treat just half of the known rare diseases. More than 30 million Americans are living with at least one of the more than 7,000 known rare diseases, and approximately 90 percent of those diseases have no FDA-approved treatment.
The Senate hearing produced evidence-backed solutions, and it’s essential that the FDA act on the following four mandates:
Establish a dedicated Rare Disease Advisory Committee, staffed with experts who understand the science, the use of surrogate endpoints and the rationale for ultra-small clinical trials for gene therapies.
Between 2024 and 2025, the FDA’s utilization of advisory committee meetings dropped a staggering 65 percent. The absence of informed scientific dialogue among independent physicians and academics cannot possibly help people with rare diseases.
Further, a therapy for a disease affecting an orphan population shouldn’t be evaluated by a committee assembled to review treatments for millions. A rare disease advisory committee is a necessity.
- The FDA must commit to consistently utilizing the accelerated approval pathway when criteria are met. Expedited reviews exist because Congress recognized that rare disease patients cannot wait for perfect data or ideal trial circumstances. Without consistent utilization of these critical regulatory review protocols, patients are left waiting on a promise that the FDA has yet to consistently keep.
- Issue and adhere to guidance on the use of surrogate endpoints in rare disease clinical trials. Sponsors need to know what is expected before they invest time and capital in a trial that may be negated in the course of a single meeting. Shifting expectations mid-cycle only serves to stop innovation before it has a chance to help patients.
- Increase transparency around late-stage review changes and rejection rationale. When a sponsor receives a CRL after years of development aligned with agreed-upon guidance, both they and patients deserve a clear, evidence-backed explanation.
Nobody at the hearing asked the FDA to lower its standards. They only want the agency to apply the tools and protocols it already has, and to do so consistently, under the leadership of experts who understand the nuances of rare disease drug development and will approach the process from a more open perspective than Prasad did.
When a patient and their family hear “accelerated approval pathway,” they have hope and assume regulators are following a roadmap to a treatment. Witnesses testified that the FDA’s roadmap is full of obstacles, and while the agency has the authority to clear them, to date, it has failed to do so.
Rare disease science will never be perfect. The Senate understands this—on Tuesday, Sen. Ron Johnson (R-WI) reportedly launched an investigation into the FDA’s recent rare disease drug rejections—and so do physicians, advocates, caregivers and patients.
Now the FDA needs to act like it does, too.
