84% of Investors Are Pulling Back from Rare Disease. Here Is Why That Should Alarm Every Patient.

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 that included 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 can translate 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.

Reuters reported on April 1, 2026 that CBER approved 5 orphan drugs in 2025 while issuing 4 Complete Response Letters and 1 comparable setback before a marketing application. By that count, 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. Reuters reported on April 1, 2026 that the FDA's drug evaluation center (CDER) had 8 approvals and 2 CRLs over the same period, without saying whether those counts cover only rare disease drugs. BioSpace reported on April 2, 2026 that Stacey Frisk of the Rare Disease Company Coalition put CDER's rare disease approvals so far that year at 4.

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%. On October 22, 2026, Biohaven said the FDA had accepted a resubmitted application for review, with a decision expected in the first quarter of 2027. Atara Biotherapeutics received a second CRL for tabelecleucel (Ebvallo) for EBV-positive post-transplant lymphoproliferative disease in January 2026. The companies said the FDA's reasons were at odds with its earlier exchanges with them, STAT reported on February 25, 2026. STAT described the condition as one that can leave patients with 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 is now reviewing 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, which uniQure said went against years of prior discussions with the agency. According to uniQure, 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, left the agency 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. STAT reported on October 31, 2025 that agency officials described CBER as rife with mistrust, and that employees said Prasad had pushed at least 7 senior leaders out of their positions.

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 open question is whether the next CBER director will use those tools more often than the coalition says CBER did in 2025.

“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. When the money stops, programs can be shelved or canceled.

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. Across the industry, cuts like this can push long-running programs down the list or end them. 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 CBER rejects about half of late-stage rare disease programs, as Reuters reported for 2025, and when 84% of investors in a coalition survey say they pulled 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 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.

Updated October 14, 2026 to credit the sources of the drug center counts and the leadership report, and to add why Regenxbio's gene therapy was put on hold. Updated October 22, 2026 to add the FDA's acceptance of Biohaven's troriluzole resubmission.