FDA Official Pushes Back in UniQure Dispute
A senior FDA official sharply criticized UniQure’s investigational gene therapy for Huntington's disease, calling it a “failed product” during a 3/5 conference call with reporters and intensifying doubts about the treatment’s regulatory prospects, according to Reuters. The remarks came days after the company said FDA had asked it to conduct a new clinical trial to support approval of the therapy, rejecting the company’s most recent study because it did not include a placebo-controlled arm.
The FDA official, who spoke on condition of anonymity, said an earlier company-run trial that used a placebo design produced negative results. “It was stone cold negative,” the official said. “We have a failed product here.”
At the center of the dispute is UniQure’s reliance on an external dataset of Huntington’s patients rather than a concurrent placebo group to evaluate the therapy’s effectiveness. In September, the company said its studies showed the treatment slowed disease progression by 75% after three years, based on a standard clinical rating scale, when compared with patients in an external database. The FDA official said such a comparison was unacceptable, noting the agency has “never in 25 years” approved a Huntington’s therapy based on that type of trial design, according to Reuters.
“We do not dispute the claim that it is 75% better than those people,” the official said. “What FDA disputes is that those people are a fair comparator.” The agency official also accused the company of presenting a “distorted or manipulated comparison” in its data analysis.
During the call, the FDA official defended the agency’s insistence on a new randomized trial, saying such designs are necessary in diseases like Huntington’s where outcomes can vary widely and subjective endpoints may be influenced by expectations, according to a FierceBiotech report.
“We only ask for randomized data when a condition is heterogeneous, when the will to believe is strong, when the therapy is invasive or potentially harmful, when the effect size is difficult to detect and when the possibility you are fooling yourself is high,” the official said.
AMT-130 is administered through neurosurgery, in which surgeons make a skin incision, drill into the skull and inject the gene therapy into the brain. According to the FDA official, the agency asked UniQure to randomize patients either to receive the full treatment procedure or to a limited sham control in which patients would be anesthetized and receive small scalp incisions but no cranial drilling or brain injection.
“We asked UniQure to take their product and randomize patients to getting the treatment the way they give the treatment … versus a control arm, where all they do is anesthetize the patient and put one to three nicks in the scalp,” the official said. The procedure for the control arm could theoretically be completed in about 30 minutes under anesthesia, the official added. FDA did not ask the company to conduct a more invasive “partial sham burr hole” procedure, the official said.
UniQure has argued that the agency previously agreed the company could rely on an external control group as the primary basis for an approval application. But the FDA official disputed that claim, saying the agency has long required internal control groups in Huntington’s disease trials, according to FierceBiotech.
“That’s been the long-standing policy for at least two decades,” the official said. The official said agency staff reviewed records of meetings with the company and found no documentation supporting UniQure’s claim that the FDA had promised to accept an external comparator.
“Did FDA ever agree to accept this distorted comparison? No,” the official said. “I’ve asked our people to look for any written or verbally transcribed or minutes of a meeting that document such a promise, and there is no such promise made.”
The official added that regulators rarely provide assurances about approval pathways in advance. “FDA will always say, ‘Well, we have to see the data when we get it,’” the official said.
The regulatory pushback has drawn criticism from patient advocates. The Huntington's Disease Society of America warned that requiring a new placebo-controlled trial could impose heavy burdens on patients with the rapidly progressive neurological disorder. The advocacy group said requiring participants to spend two years in a control arm without receiving the therapy would not be a neutral observation period but rather “a period of active, irreversible neurodegeneration.”