After a string of high-profile regulatory rebukes, Biohaven’s CEO believes red tape is getting in the way of patient well-being, particularly for those with rare diseases.
Months after the FDA rejected Biohaven’s bid to approve its spinocerebellar ataxia (SCA) therapy, CEO Vlad Coric, M.D., says the decision is part of a broader shift at the agency that may stifle innovation.
“This is a systemic problem that we saw at the FDA last year and continue to see,” Coric told Fierce Biotech on Wednesday.
“This is not a Biohaven issue,” he continued, citing “other rare disease issues,” such as the FDA’s refusal to approve Regenxbio’s Hunter syndrome gene therapy based on concerns about several trial design features, such as the use of a natural history control arm.
Other issues include Stealth BioTherapeutics’ laborious back-and-forth with the regulator that ultimately ended in an approval for the ultrarare Barth syndrome after numerous rejections. The tides eventually changed for StealthBio after the FDA faced wide-ranging public outcry regarding its delays and prior snubs for the rare disease candidate.
Biohaven’s CEO also mentioned the FDA’s hotly contested decision to refuse review for Moderna’s next-gen flu vaccine this week.
“It’s really a dire time for patients,” he said, explaining that Biohaven is currently appealing the agency’s decision. But, if the FDA doesn’t provide a path forward, the program will cease to exist, he said.
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“There’s 300 patients who are on compassionate use,” the CEO said, referring to the participants of Biohaven’s neuro study.
The phase 3 trial assessed troriluzole in SCA, a progressive genetic disease that impacts movement and speech ability. It is believed that one to five individuals have the condition per 100,000 people worldwide. There currently aren’t any SCA-specific treatments available.
“Some of them have taken this for eight years,” Coric said about the patients receiving troriluzole. “With a program that ends, drug supply will be over at some future point, and people will come off the drug and people get worse.”
Biohaven’s study of troriluzole failed to meet its primary goal, which measured change in baseline at the 48-week mark on a disease-specific scale determining the loss of coordination and level of impairment in patients with SCA. Initially, the company had taken those data to the FDA with a request for approval that was denied in 2023.
Despite the setback, Biohaven continued to seek a path forward, leading to talks with the FDA about the potential to use real-world evidence (RWE) to support a resubmission. Biohaven hailed positive three-year RWE findings in September 2024.
“The study that they accepted under priority review won statistically on its primary and eight secondary endpoints,” Coric said. “Irrefutable.”
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That filing was the basis of the most recently rejected application, Coric explained. In 2024, the FDA had reviewed the study protocol and statistical analysis plan before the filing and said, “If you win with a large and robust effect size, it will account for the bias that one could attribute to real-world evidence, external control,” according to Coric.
But that FDA was under different leadership, with President Donald Trump-appointed Marty Makary, M.D., taking the helm of the agency last year. Makary’s FDA delivered the complete response letter (CRL) to Biohaven, citing “issues that can be inherent to real-world evidence and external control studies including potential bias, design flaws, lack of pre-specification and unmeasured confounding factors.”
Paired with the agency’s change in heart for uniQure’s gene therapy trial, William Blair analysts at the time voiced concerns about the possibility that the FDA is “becoming more restrictive despite sponsors aligning on prior feedback.”
“We felt as though we had all—we played by all the rules, we followed all the regulations, and we won. But we were given a CRL because of a subjective interpretation,” Coric recalled.
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He went on to describe the letters as lacking transparency, a claim that opposes Makary’s stated commitment to making transparency a central pillar of the agency’s leadership.
“We had answers to every one of those CRL items—we have put in so much data,” Coric said. “There’s no transparency in these CRLs, it’s a one-sided view to reinforce the decision that was made, right? They even block out the name of the person who signed it. Like, how is that transparent?”
When asked why he thinks the agency decision change-ups are occurring, Coric said he didn’t have a clue.
“All I can comment on is Congress through the [21st Century Cures Act], is very clear about how you’re supposed to handle regulatory flexibility in these rare diseases, especially when there’s no treatment, there’s good biologic reason and it’s a life-threatening illness,” he said, adding, “And those regulations are not being followed.”
The 2016 act Coric mentioned is designed to aid in the development and delivery of medical treatments.
“Patients are being denied care because of bureaucratic red tape, and none of us understand why,” Biohaven’s CEO added.
Overall, the recent pattern occurring at the FDA will likely hurt innovation for biomedical products in the U.S., according to the Biohaven CEO, a sentiment several others have voiced this week in light of the agency’s Moderna decision.
“This has been one of, traditionally, the greatest industries that America has had,” Coric said of biotech. “And I think we’re negatively being affected by what’s going on.”
When asked whether bureaucratic red tape was getting in the way of helping patients and ultimately denying care for patients in some cases, Department of Health and Human Services’ (HHS’) Andrew Nixon told Fierce Biotech that, “The premise of these claims is incorrect.”
“The FDA evaluates scientific evidence to ensure treatments are safe and effective,” the HHS spokesperson said. “Protecting patients requires rigorous standards, and that responsibility will not be compromised.”
Looking back, the Biohaven CEO says he stands by the troriluzole data.
“We believe that drug should have been approved,” he said.
As for steps forward, Biohaven is currently in the appeals process with the FDA but won’t continue with the asset unless the agency provides a path for the company to do so.
“We’ve been at this [for] eight years. It doesn’t make sense—we can’t do another eight years,” Coric explained. “You can’t spin your wheels forever in an area. You have to move on.”
Back in November, after receiving the CRL, Biohaven slashed its R&D spend by 60% and named a myostatin-targeting obesity asset as its main program.
“We’re trying to work with the FDA, and we’re engaged in that,” Coric said about the company’s SCA program. “We have not seen the constructive collaboration with us but we will keep at it.”
“It’s the patients who suffer,” he concluded. “What are they going to do without a path forward?
