The FDA has reversed its opposition to the regulatory pathway for what could become the first disease-modifying therapy for Huntington’s disease, agreeing that three-year data from a Phase I/II trial of UniQure’s gene therapy AMT-130 can serve as the primary basis for a Biologics License Application under the accelerated approval pathway.
The decision, reached during a Type B meeting on June 17, marks a dramatic shift from the FDA’s position just three months earlier. In March 2026, the agency had told UniQure that the early-stage data, combined with an external control arm, was not sufficient for a marketing application and recommended a new randomized, double-blind, sham-controlled Phase III trial instead. The earlier rejection was associated with the tenure of former FDA Commissioner Marty Makary and former CBER director Vinay Prasad, both of whom have since departed the agency.
AMT-130 is a one-time gene therapy delivered via MRI-guided stereotactic injection directly into the striatum. It uses an AAV5 viral vector to deliver an artificial microRNA designed to silence the huntingtin gene, the genetic culprit behind Huntington’s disease, a fatal neurodegenerative disorder caused by a CAG repeat expansion in the HTT gene.
The 36-month data from the high-dose cohort showed:
- A 75% slowing of disease progression on the composite Unified Huntington’s Disease Rating Scale (cUHDRS, p=0.003)
- A 60% slowing on the Total Functional Capacity score (p=0.033)
- An 88% slowing on the Symbol Digit Modalities Test (SDMT), a measure of cognitive function (p=0.057, a trend)
- 113% slowing on the Stroop Word Reading Test (p=0.002)
- Cerebrospinal fluid neurofilament light chain (NfL), a biomarker of neuronal damage, declined 8.2% from baseline at 36 months
“These are the most convincing data we have seen in the field to date,” said Sarah Tabrizi, a professor at the UCL Huntington’s Disease Center, who was not involved in the study.
The regulatory path forward
UniQure now plans to submit its BLA in the third quarter of 2026. AMT-130 already holds RMAT (Regenerative Medicine Advanced Therapy), Breakthrough Therapy, Fast Track, and Orphan Drug designations from the FDA, all of which confer priority review and enhanced regulatory support.
The accelerated approval pathway means that UniQure will need to conduct a confirmatory post-marketing study. The FDA and the company are working to align on a study design that moves from the previously proposed sham-controlled approach toward a concurrent standard-of-care control.
The broader context
The reversal comes at a moment of intense scrutiny around the FDA’s decision-making on gene therapies. The rejection in March was part of a pattern under the Makary-Prasad leadership that saw multiple rare-disease and gene therapy applications face unexpected hurdles, decisions that were publicly questioned by patient advocacy groups and some members of Congress.
Huntington’s disease affects approximately 30,000 people in the United States and an estimated 200,000 worldwide. It is caused by a single dominant genetic mutation, making it a theoretically ideal target for gene silencing approaches. Despite decades of research, no disease-modifying therapy exists. Current treatment is limited to symptomatic management of chorea (involuntary movements), psychiatric symptoms, and cognitive decline.
Disclosure: This article is based on company announcements and clinical trial data from uniQure. As of publication, the 36-month Phase I/II data have not yet appeared in a peer-reviewed journal. The trials are registered at ClinicalTrials.gov (NCT04120493 and NCT05243017).
Source: STAT News, “New hope in treating Huntington’s disease and a report card on RFK Jr.’s promises” (June 18, 2026). https://www.statnews.com/2026/06/18/huntingtons-disease-uniqure-rfk-jr-readout-loud-podcast/