UniQure Seeks FDA Approval for Huntington's Gene Therapy

UniQure has submitted applications to the U.S. Food and Drug Administration for its AMT-130 gene therapy, aiming for the first approved treatment targeting the underlying cause of Huntington's disease. The Dutch company also completed a submission with U.K. Regulators and is asking the FDA for a priority review, which could yield a decision in about eight months.

The submission is based on previously announced three-year data indicating AMT-130 could significantly slow signs of disease progression. UniQure is seeking an accelerated approval, which would require the company to later supply confirmatory research proving the therapy's clinical benefits.

A Year of Regulatory Shifts

The move comes almost a year after UniQure first announced its intent to seek approval, a declaration that tripled its share price. That initial optimism was tempered by a drastic change in the FDA's stance last November. New agency leadership, having replaced officials from the Biden administration who had signed off on the research plan, expressed doubts that UniQure's data could support an application.

The core issue was the company's use of an external control group for comparison. Instead of using an in-study control group of patients who received a sham surgery, UniQure compared its three-year data from treated patients against a natural history database called Enroll-HD.

The Sham Surgery Debate

AMT-130's administration requires an hours-long surgical procedure. The company had initially included a sham surgery control group but later, with what it believed was FDA agreement, switched to the external database. By March of this year, the FDA clarified it wanted a new double-blind trial featuring a sham surgery control, a requirement that raised significant ethical concerns.

This period was marked by public conflict, including federal health officials criticizing UniQure and an anonymous FDA official, widely believed to be Vinay Prasad, discussing the case with journalists. Prasad's departure from the agency and the May resignation of FDA Commissioner Marty Makary followed.

A Path Forward for AMT-130

Interim FDA leadership has since worked to stabilize the agency's review process. In June, UniQure stated the FDA now believes its original three-year dataset is sufficient to seek approval. Analysts note that while regulatory risk persists due to leadership changes, the company and the agency appear aligned on the design of the necessary confirmatory study.

Crucially, the planned trial will not require a sham surgery control group. Avoiding a sham procedure should make the study considerably more practical to enroll and removes a meaningful ethical and execution hurdle, wrote Leerink Partners analyst Joseph Schwartz in a client note.

William Blair analyst Sami Corwin pointed out that some regulatory risk remains, given the continued leadership changes at the FDA. The next major milestone for the program is expected four-year follow-up data, due by the end of the month.