The back-and-forth between the FDA and gene therapy developer uniQure is getting messier, with an agency spokesperson now denying the biotech’s claims about a sham trial request for the rare Huntington’s disease.
Earlier this week, the biotech’s stock crashed after confirming that the FDA rejected its data package for AMT-130, a highly anticipated gene therapy for the progressive neurodegenerative disease.
The Danish drugmaker said it plans to discuss the design of the potential phase 3 trial with the FDA at an upcoming type B meeting, uniQure Chief Medical Officer Walid Abi-Saab, M.D., said during a March 2 call with investors. But Abi-Saab was also clear that such a trial, involving some patients with the fatal disease receiving sham surgery and no treatment, presents risks and serious ethical quandaries.
Patients would need to be “anesthetized for an extended period of time” while surgeons “superficially drill a hole in the skull,” Abi-Saab said, only to then wait two or three years before learning they’d been in the placebo group.
“Potentially at the end of this period, they might have progressed enough that they cannot benefit from the drug or they will never really get back” to the functioning they had before the sham surgery, he said.
As a result, uniQure is “very keen” to work with the FDA, Abi-Saab added. “We know that the FDA definitely cares about patients. They indicated that. We just want to work with them and appeal to their flexibility.”
On Wednesday, Department of Health and Human Services spokesperson Andrew Nixon called uniQure’s description of the sham surgery false on social media.
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“The company’s description of what the control arm participants are going through is completely distorted,” Nixon wrote on X.
In response to another user who said that sham surgery for Huntington’s disease “isn’t logical,” Nixon doubled down.
“The company already conducted a sham trial of what we are asking,” he responded, referring to the 10 patients given sham surgery in the phase 1/2 trial. “Why don’t you read up on your history? Or maybe you’re too old and forget.”
After plummeting 40% following the rejection of AMT-130, uniQure’s share price has edged up slightly today. From yesterday’s close of $9.04 per share, the biotech’s stock was trading at $10.17 as of 11 a.m. ET.
As of publication, uniQure has declined to respond to Fierce Biotech’s request for comment.
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In late February, several witnesses testified at a congressional hearing about the challenges of conducting placebo-controlled trials for diseases that affect such a small number of patients.
After the FDA rejected Biohaven’s experimental drug troriluzole in spinocerebellar ataxia (SCA), Jeremy Schmahmann, M.D., a professor at Harvard Medical School and founding director of Massachusetts General Hospital’s Ataxia Center, said the agency asked the company to conduct a placebo-controlled trial for the rare neurodegenerative disorder.
“The FDA-proposed path forward is another placebo-controlled trial that will take five to eight years, or a randomized withdrawal of [the] drug from patients benefiting from it. If this happens, patients on placebo will die,” Schmahmann testified. “I believe this to be unethical, lacking charity, mercy or kindness.”
Another testifying witness was Cara O’Neill, M.D., a pediatrician who serves as the chief scientific officer of the Cure Sanfilippo Foundation, a nonprofit for patients impacted by the genetic form of childhood dementia. O’Neill helped form the foundation after her daughter, Eliza, received a Sanfilippo diagnosis in 2013.
“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,” O’Neill said. “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 added.
In response to the contentious series of events at uniQure, Portnoy Law Firm is filing a class-action suit against the biotech on behalf of investors who purchased uniQure stock in the fall of 2025. The firm says it pursues cases against corporate wrongdoing, and highlighted uniQure’s Nov. 3 press release in which the company said the FDA appeared to change its tune on the one-time therapy and that the phase 1/2 data gathered may no longer be enough to file for approval.
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National securities law firm Faruqi & Faruqi is also investigating potential claims against uniQure for making “false or misleading statements” around its trial design and FDA communications. The legal firm has also launched an investigation into Regenxbio, which recently received an FDA refusal for its gene therapy in the rare disease Hunter syndrome.
Since the beginning of last year, the FDA has handed down 23 rejections for new rare disease treatments, Annie Kennedy, chief mission officer for EveryLife Foundation for Rare Diseases, testified during the Senate hearing. She added that many of those candidates were under accelerated approval, suggesting a “hesitation to apply regulatory flexibility through surrogate endpoints, natural history studies and external controls.”
“Congress has provided the agency with significant regulatory flexibility to encourage both biotech innovation and rare disease therapies,” Sen. Kirsten Gillibrand, D-N.Y., said during the hearing, which focused on federal red tape that may be blocking rare disease innovation and approvals.
“These mechanisms are designed to help improve access to novel treatments for our patients… But it’s not working how it should be,” the senator said, citing “a pattern of hesitation to use authorized flexibilities,” limited communication with sponsors and last-minute shifts in regulatory positions around trial design.
