On April 1, 2026, the Rare Disease Advocacy, Biotechnology, and Investor Coalition (RDBI) sent a letter to President Trump, Health Secretary Robert F. Kennedy Jr., Medicare Chief Mehmet Oz, and FDA Commissioner Marty Makary. The coalition, made up of nearly 100 rare disease patient advocacy groups, biotech executives, and investors, asked the administration to restore regulatory clarity for rare disease therapies as new leadership is considered at the FDA's Center for Biologics Evaluation and Research (CBER).
The letter came at a critical moment. CBER's director at the time, Vinay Prasad, was due to leave the FDA at the end of April after a tenure defined by high-profile disputes over vaccine reviews, gene therapies, and rare disease drug applications. He has since left. Karim Mikhail, who had been running CBER in an acting role, was named its permanent director on September 8, 2026, according to HHS. The data the coalition presented paints a picture that should concern anyone connected to the rare disease community.
Those numbers are not abstract. They translate directly into fewer clinical trials, slower drug development timelines, and fewer treatment options reaching the patients who need them most.
The Rejection Rate Has Changed Dramatically
The core of the coalition's concern is a sharp shift in how CBER has handled rare disease drug applications. The numbers tell the story clearly.
In 2025, CBER approved 5 orphan drugs while issuing 4 Complete Response Letters and 1 comparable setback at the pre-application stage. That means roughly half of late-stage rare disease programs were rejected, compared to just 1 CRL among 20 programs over the prior 2 years.
The first quarter of 2026 continued the trend. CBER approved 1 orphan drug (Rocket Pharmaceuticals' gene therapy Kresladi for leukocyte adhesion deficiency-I) and issued 2 more CRLs. For comparison, the FDA's drug evaluation center (CDER) approved 8 drugs and issued only 2 CRLs over the same period.
The Companies and Patients Affected
These are not numbers on a spreadsheet. Each CRL represents a therapy that patients were counting on, and in many cases a company that spent years and hundreds of millions of dollars getting to the finish line.
Biohaven's troriluzole for spinocerebellar ataxia was rejected in November 2025 by the FDA's drug center, CDER, after what Biohaven called 8 years of development work. Biohaven reported that the drug slowed disease progression by 50% to 70% compared with untreated patients from outside databases, a comparison the FDA said had possible bias and design flaws. It would have been the first approved treatment for SCA. Biohaven said the same day it would cut its direct R&D spending by about 60%. Atara Biotherapeutics received a second CRL for tabelecleucel (Ebvallo) for EBV-positive post-transplant lymphoproliferative disease in January 2026, after the FDA reversed its position on a trial design it had previously confirmed as adequate. That condition gives patients weeks or months to live. Pierre Fabre, which now leads the application, resubmitted it on September 30, 2026.
Capricor Therapeutics' cell therapy deramiocel for Duchenne muscular dystrophy cardiomyopathy was rejected in July 2025. (The FDA has since reviewed a resubmission. After a 9 to 3 negative advisory vote on the heart indication in July 2026, Capricor amended the application to focus on upper limb function, and the decision is now due November 22, 2026.) UniQure's gene therapy for Huntington's disease was effectively pushed back when the FDA, under its previous leadership, signaled that a new randomized, sham surgery-controlled study would be needed, despite years of prior engagement. The FDA later agreed that 3-year data from the early-stage trial could support an application, and uniQure submitted it for accelerated approval on September 2, 2026.
Why the Leadership Transition Matters
Vinay Prasad's tenure at CBER was turbulent by any measure. He was appointed in May 2025, resigned under pressure in late July after backlash from rare disease advocates and political figures over his handling of a Duchenne muscular dystrophy treatment, then returned about 2 weeks later at FDA Commissioner Makary's request. Internal reports described a work environment of mistrust, with at least 7 senior leaders pushed out of their positions during his time.
His departure created both a risk and an opportunity. The coalition's letter is essentially asking: who comes next, and will they understand that rare disease drug development cannot be held to the same evidentiary standards as drugs for large, well-studied populations? Rare diseases affect small numbers of patients. Traditional large-scale randomized trials are often impossible. The FDA has historically recognized this through mechanisms like accelerated approval, Priority Review, and Orphan Drug Designation. The question is whether the next CBER director will use those tools or continue to tighten the bar.
“We believe it is of the utmost importance that the FDA chooses a leader who understands the unique challenges of rare disease development and respects and values the views of patients and physicians.”
RDBI Coalition letter to President Trump
The Investment Problem Is a Patient Problem
It is easy to dismiss investor sentiment as a Wall Street concern, but in rare disease, the connection between investment and patient access is direct. Most rare disease therapies are developed by small and mid-cap biotech companies that rely on venture capital, public equity, and grants to fund their research. When investors lose confidence in the regulatory pathway, the money stops flowing. And when the money stops, programs get shelved or canceled entirely.
The Priority Review Voucher (PRV) program, which had been a critical financial incentive for rare pediatric disease development, lapsed in late 2024 before being reauthorized in February 2026. In a Rare Disease Company Coalition survey reported by BioSpace on January 26, 2026, 35% of biotech executives said they had canceled or delayed programs since the voucher program lapsed, and 85% said the voucher had been a significant factor in pursuing rare pediatric disease assets. The program has been extended through September 2029, but the damage from the lapse compounded an already difficult environment.
Biohaven's 60% R&D cut after the troriluzole CRL is a real-world example of what happens when regulatory uncertainty meets financial pressure. Programs that were in development for years get deprioritized or abandoned. The patients who would have benefited from those therapies have no say in the decision.
What Rare Disease Patients Can Do About FDA and Funding Shifts
For anyone living with a rare disease or caring for someone who is, this situation is deeply personal. The regulatory and investment environment may feel far removed from daily life, but it determines which drugs get developed, which trials open, and which treatments ultimately become available.
According to the National Institutes of Health and National Organization for Rare Disorders, there are roughly 7,000 known rare diseases, and treatments exist for fewer than 5% of them. For the other 95%, patients are waiting for research to catch up. When the FDA's approval rate for rare disease drugs at CBER drops from about 90% to about 50%, and when 84% of the people funding that research pull back, the timeline for those treatments stretches further into the future.
The coalition's letter is a formal expression of what many in the rare disease community already feel: the system meant to protect patients is, in some cases, preventing them from accessing therapies that could meaningfully change their lives. The hope is that the next chapter at CBER brings the kind of leadership that holds rigorous standards while also recognizing that for progressive, life-threatening conditions with no alternatives, the cost of inaction is not zero.