FDA clears UniQure path for Huntington’s gene therapy filing
UniQure says regulators accepted a control-group plan for AMT-130 after an earlier sham-surgery demand drew sharp criticism.
By Hana Yoshida · Markets Reporter
3 min read
UniQure says the Food and Drug Administration has again agreed to let the company seek accelerated approval for its Huntington’s disease gene therapy without running a sham-surgery control arm. The decision gives AMT-130 a renewed regulatory path after a prior FDA demand raised ethical objections because the treatment is delivered through brain surgery.
Ars Technica reported that Huntington’s disease is an inherited disorder that generally appears in middle age and causes progressive damage to nerve cells in the brain. Ars Technica also reported that there are no current treatments for the disease and that many people affected die in their 50s or 60s.
According to UniQure, AMT-130 is designed as a one-time therapy that lowers levels of mutant huntingtin, the protein linked to Huntington’s disease. The company has said data from a small early-stage study suggested the treatment could slow disease progression by as much as 75 percent.
A dispute over trial controls
Ars Technica reported that the FDA told UniQure in 2024 that the company could submit AMT-130 for accelerated approval without a placebo control arm. UniQure then used an external comparison group of untreated patients, believing regulators had accepted that approach, according to the report.
The trial-design issue carried unusual ethical weight because AMT-130 requires a 10- to 12-hour brain operation, Ars Technica reported. A sham-surgery control arm would have meant some participants could undergo a lengthy procedure without receiving the treatment, including possible drilling of a superficial hole in the skull, according to the report.
During Vinay Prasad’s tenure as the FDA’s top gene-therapy regulator, the agency rejected that plan and required sham surgeries as controls, according to UniQure documents cited by Ars Technica. Ars Technica reported that Prasad’s time in the role included accounts that he overruled staff scientists and career officials, surprising companies and changing regulatory expectations.
Janet Woodcock, a retired FDA official who spent nearly 40 years at the agency, criticized the sham-surgery requirement as “truly evil,” according to The New York Times account cited by Ars Technica. Ars Technica reported that Prasad later attacked UniQure and Woodcock at a press briefing, calling AMT-130 a “failed therapy,” accusing the company of manipulating data and saying he expected better from Woodcock.
Then-FDA Commissioner Marty Makary announced one day after that briefing that Prasad would leave the agency by the end of April, Ars Technica reported. Makary and Tracy Beth Høeg, who had been the agency’s top drug regulator, also later left amid controversy, according to Ars Technica.
Company plans third-quarter filing
UniQure said in a press release that a recent FDA meeting restored the company’s ability to use a control group made up of patients receiving standard care rather than sham surgery. The company said it expects to file for accelerated approval in the third quarter of this year.
UniQure CEO Matt Kapusta said in the company’s statement that the announcement reflected the outcome the company had sought in talks with the FDA. Kapusta said UniQure remains focused on bringing AMT-130 to patients and families in the United States and globally as quickly and responsibly as possible.
This story draws on original reporting from Ars Technica.