A panel of physicians, biotech leaders and patient advocates took aim at the FDA during a Senate hearing Thursday on how the agency’s bureaucracy affects innovation, with one witness testifying that engaging with regulators was “like talking to a brick wall.”
“I wrote six letters to FDA leadership between 2023 and 2025 cosigned by 17 ataxia colleagues asking FDA to review the application again and work with Biohaven to make the drug available [and], if necessary, performing post marketing studies. I never heard back,” Jeremy Schmahmann, M.D., a neurology professor at Harvard Medical School and founding director of Massachusetts General Hospital’s Ataxia Center, said during the hearing chaired by Sen. Rick Scott, R-Fla.
In November, the regulatory agency denied approval for Biohaven’s experimental drug troriluzole in spinocerebellar ataxia (SCA), a progressive genetic disease that impacts movement and speech ability. There currently aren’t any SCA-specific treatments available.
After an initial phase 3 miss, Biohaven continued to seek a path forward, leading to talks with the FDA about the potential to use real-world evidence to support a resubmission.
“The study that they accepted under priority review won statistically on its primary and eight secondary endpoints,” Biohaven CEO Vlad Coric, M.D., told Fierce Biotech a few weeks ago. Despite the priority review path, the FDA delivered a rejection, citing “issues that can be inherent to real-world evidence and external control studies.”
Biohaven is currently appealing the agency’s decision, but, if the drug isn’t approved, the program—and experimental treatment—will cease to exist.
“The FDA worked with the company initially, but then they changed their mind later,” Schmahmann said Thursday. “Now, 300 patients stable on troriluzole will have to come off drug, and they are destroyed.”
“The FDA-proposed path forward is another placebo-controlled trial that will take five to eight years, or a randomized withdrawal of drug from patients benefiting from it. If this happens, patients on placebo will die,” the ataxia specialist continued. “I believe this to be unethical, lacking charity, mercy or kindness.”
Schmahmann underscored troriluzole’s well-tolerated safety profile and that both physicians and patients have testified to its efficacy.
“I met three times with [the] FDA Center for Drug Evaluation and Research,” he said. “On each occasion, they did not heed the patients or the experts or consider the science. One panel member said to me, ‘Why should I listen to you?’”
Compassion is a prerequisite for regulatory officials when they’re considering rare disease programs and patients, according to Schmahmann, who added, “I saw none of that in the three meetings with the FDA.”
“The members of the panel were like talking to a brick wall,” he said. “There was no engagement, no dialogue. In fact, they said as much: ‘This is not a dialogue; this is not a collaboration.’”
“They did not seem to see the suffering of the patients, and they didn’t hear the science. They were rigid and inflexible and unyielding,” Jeremy Schmahmann, M.D., a neurology professor at Harvard Medical School and founding director of Massachusetts General Hospital’s Ataxia Center, said.
“Senators, please save our patients’ lives,” the neurologist said. “Use your authority to require that FDA consider real-world evidence and applies the regulatory flexibility you have legislated and, in so doing, restore transparency, integrity and competence to the agency.”
Another testifying witness, Cara O’Neill, M.D., shared a contrasting experience about her communications with the FDA.
O'Neill, a pediatrician, serves as the chief scientific officer of the Cure Sanfilippo Foundation, a nonprofit raising money and awareness for patients impacted by a genetic form of childhood dementia known as Sanfilippo syndrome.
“My interactions with regulators have been kind, so maybe a bit of a different perspective,” she said after Schmahmann’s testimony. “They have been interested to hear what we had to say, to hear the patient perspective.”
O'Neill, who helped form the Cure Sanfilippo Foundation after her daughter Eliza received a Sanfilippo diagnosis in 2013, continued, “Where we’re challenged is that we don’t see that translated into regulatory action, and some of the decisions that are coming out [of the agency] are not benefiting patients right now.”
“Listening is great, but two-way conversation and collaboration is actually what’s needed,” said Cara O’Neill, M.D., chief scientific officer of the Cure Sanfilippo Foundation, adding that she also wants to see more transparency on “how patient experience, data and patient input is actually being integrated into these decisions.”
When reached for comment, U.S. Department of Health and Human Services (HHS) spokesperson Andrew Nixon said, “The FDA works closely with sponsors throughout the review process and remains committed to bringing safe and effective therapies to patients with rare diseases as efficiently as the law and the science allow.”
Results in recent rare disease regulations
“Since the start of 2025, we have seen at least 23 complete response letters declining to approve rare disease therapies, many under accelerated approval that suggest a hesitation to apply regulatory flexibility through surrogate endpoints, natural history studies and external controls,” testified Annie Kennedy, chief mission officer for EveryLife Foundation for Rare Diseases.
Many of those 23 complete response letters—rejections to a request for FDA approval—are reversals of previous regulatory agreements that had been made with sponsors, as in the case of Biohaven, the patient advocate continued.
Meanwhile, advisory committee meetings for drugs and biologics dropped by 65% from 2024 to 2025, “reducing opportunities for external expertise and patient insights to inform complex, rare disease product decisions,” Kennedy said.
Historically, advisory committees are convened when there is a complex decision that needs to be worked through between a sponsor and the agency, she explained.
The FDA hasn’t held any advisory committee hearings since July of last year, Kennedy said.
The HHS spokesperson told Fierce that the advisory committee meetings are held “when they are necessary to inform regulatory decision making.”
When asked about the importance of advisory committee meetings to the rare disease community, Kennedy said, “It’s everything.”
She pointed to a committee convening in 2024, for example, that “helped inform a key regulatory decision for the Barth syndrome community” by allowing patients and families to “illuminate the nuance of a very complex regulatory decision.”
In September 2025, the FDA approved Stealth BioTherapeutics’ treatment for the ultrarare condition, marking the peptide as the first therapy for Barth syndrome. But the decision followed a path of tumult and delay, including multiple approval rejections.
“The point is for external experts—including clinicians, including those with statistical expertise and manufacturing expertise that are not always internal to the agency—to be brought to bear on regulatory decisions, because we realize that with 10,000 rare diseases, it is not possible for FDA to always have all of that expertise internal,” Annie Kennedy, chief mission officer for EveryLife Foundation for Rare Diseases, said.
“What we have here is denying of the patient’s story,” Schmahmann added after Kennedy.
“If you’re ignoring the patient, then why are you getting up in the morning and coming to do the work that you do with the FDA?” he asked.
Rare disease context and calls for change
About 1 in 10 Americans are living with a rare disease, Sen. Kirsten Gillibrand, D-N.Y., ranking committee member, said in her introduction to Thursday’s event.
“Congress has provided the agency with significant regulatory flexibility to encourage both biotech innovation and rare disease therapies,” Gillibrand said, citing authorized approaches such as the accelerated approval pathway and use of real-world evidence for drug reviews.
“These mechanisms are designed to help improve access to novel treatments for our patients, and they’re supposed to provide drug sponsors with a predictable and consistent approach to addressing regulatory science challenges that are unique in rare disease, therapy, development and review. … But it’s not working how it should be,” the senator said.
Gillibrand cited a smattering of approaches to transparency across FDA centers, “a pattern of hesitation to use authorized flexibilities,” limited communication with sponsors and last-minute shifts in regulatory positions around trial design.
“This is heartbreaking for patients, and it’s why we can’t afford delays and disruptions in treatment,” Sen. Kirsten Gillibrand, D-N.Y., said. “Rare diseases can progress rapidly cause irreversible harm and, in some cases, premature death.”
The legislator also highlighted increased costs and delayed timelines for biotechs impacting the viability of clinical trials, adding, “This is bad for business, and it’s bad for patients.”
Patient advocate Kennedy called on the federal government to rapidly operationalize like it did during the start of the COVID-19 pandemic.
“We believe that our rare disease community has the urgency and unmet need that matches that of a pandemic, of a crisis,” she said. “We have individuals in this room who have very limited life expectancies, and if we don’t address what’s happening in rare disease with that same sense of urgency, they would not be here with us if we were to convene this hearing another year from now.”
Meanwhile, Amicus Therapeutics CEO Bradley Campbell used his time to present opportunities to potentially fix the current system. The rare-disease-focused biotech has programs in Pompe disease, Fabry disease and focal segmental glomerulosclerosis.
“Small and midsized biotechnology companies like Amicus, Biohaven and others are the engine of rare disease innovation, but they can only succeed if the regulatory system adapts along with unmet medical need,” Amicus Therapeutics CEO Bradley Campbell said.
He laid out “three practical areas” for improvement, starting with launching clinical trials faster.
“We know in other countries, those trials start in weeks, not months,” the biotech CEO said. “We can reduce administrative requirements, leverage single IRBs, use AI and other digital tools to get into the clinic faster.”
Campbell also said the FDA should identify better ways to measure efficacy, such as using biomarkers, innovative endpoints and accelerated approvals. Lastly, he pushed for improved manufacturing inspections.
“The single biggest delay oftentimes is inspections from getting patients access to medicines,” he said. “The FDA has tools like remote interactive inspections and relying on global regulators to reduce that inefficiency.”
‘Death by technicality’
Cure Sanfilippo Foundation’s O’Neill underscored the urgency of the matter so patients can receive the maximum benefit of treatment.
“You cannot do good medicine unless you’re putting the patients first and following the ethics of medicine,” she said, adding that the agency’s focus on ethics in animal testing is concerning when the same consideration isn’t given for rare pediatric disease trials in humans.
“What we are still hearing as recommended to sponsors is that observational or no-treatment or placebo-controlled trials are being recommended for these pediatric conditions,” she testified. “This is very, very troubling when we know that they will become brain injured.”
“We are concerned about the ethics of animal testing more than we are concerned about the ethics of allowing children to be brain injured in clinical trials, and I think we all need a gut check on that,” she continued.
“This is a policy of death by technicality, these little, tiny glitches that the FDA is producing,” Harvard’s Schmahmann said. “Patients die as a consequence.”
At the same time that the hearing was being held Thursday, FDA Commissioner Marty Makary, M.D., spoke in a CNBC interview about the agency’s approach to rare disease treatments.
In a somewhat unprecedented move, the top FDA official seemed to refer to uniQure’s gene therapy application for Huntington’s disease, which is currently under review. Data released in September showed the experimental treatment slowed the progression of Huntington’s by 75% after three years compared with an external control group based on a natural history study.
“There was a product where the researchers drilled a burr hole, literally a hole in people’s skulls, to inject intrathecally into the ventricle a therapy,” Makary said. “At the end of the randomization period, it found no benefit, and yet this is one of the drugs that we were pressured to approve.”
Some critics said his comments could have actually been about FDA-rejected Regenxbio’s gene therapy in Hunter syndrome as his description was unclear. Regardless, Makary’s comments sent uniQure’s stock spiraling from $24.80 per share at market close yesterday to $16.80 today as of 2:30 p.m. ET.
Makary also touted the FDA’s newly unveiled regulatory approach for personalized genetic medicines that is designed to accelerate the development of rare disease therapies, while praising Vinay Prasad, M.D., the controversial leader of the FDA’s Center for Biologics Evaluation and Research, which oversees vaccines and cell and gene therapies.
“Vinay Prasad is a genius,” Makary said during the interview.
HHS spokesperson Andrew Nixon did not respond to questions regarding Makary’s comments.