Huntington's First Disease-Modifying Drug Is Now One FDA Decision Away

On Nov 2, 2026, uniQure said the FDA accepted its Biologics License Application for ifezuntirgene inilparvovec, the investigational Huntington's gene therapy formerly called AMT-130. The BLA received Priority Review, with a Prescription Drug User Fee Act target action date of May 1, 2027. The company filed under the Accelerated Approval pathway, and the FDA said it is tentatively planning to discuss the application at an Advisory Committee meeting. If approved, ifezuntirgene inilparvovec would be the world's first disease-modifying treatment for Huntington's disease.

A one-time striatal infusion against a disease with no brake

There are currently no approved therapies to delay onset or slow Huntington's progression. Approximately 75,000 people in the U.S., EU, and UK have the disease, with hundreds of thousands more at risk of inheriting it. Ifezuntirgene inilparvovec is a one-time gene therapy using uniQure's miQURE platform. It delivers a microRNA designed to silence the huntingtin gene and the potentially toxic exon 1 protein fragment. Patients receive a single administration via MRI-guided, convection-enhanced stereotactic neurosurgical delivery directly into the striatum (caudate and putamen).

That delivery is neurosurgery. The most common adverse events in the program were related to the administration procedure, and all resolved. As of June 30, 2025, no new drug-related serious adverse events had been observed since December 2022. The therapy is the first Huntington's treatment to receive Breakthrough Therapy and Regenerative Medicine Advanced Therapy designations, and it also holds Fast Track designation. The Phase I/II studies dosed 51 patients in total.

The 36-month signal, without a sham comparison

The pivotal Phase I/II study met its prespecified primary endpoint. High-dose AMT-130 showed a statistically significant 75% slowing of disease progression at 36 months as measured by the composite Unified Huntington's Disease Rating Scale, p=0.003, versus a propensity score-matched external control. Treated patients had a mean change in cUHDRS from baseline of -0.38, versus -1.52 for the external control. A key secondary endpoint also met: 60% slowing of disease progression by Total Functional Capacity, p=0.033 (mean change -0.36 versus -0.88).

Other measures trended in the same direction with mixed statistical strength: 88% slowing on the Symbol Digit Modalities Test (p=0.057), 113% slowing on the Stroop Word Reading Test (p=0.002), and 59% slowing on Total Motor Score (p=0.174). Cerebrospinal fluid neurofilament light, a biomarker of neurodegeneration, fell a mean -8.2% from baseline. Twelve patients per dose group had reached 36 months of follow-up and were evaluated. The comparison used a propensity score-matched external control drawn from the Enroll-HD natural history dataset (n=940 for the high-dose comparison; n=626 for low dose), under a prespecified statistical analysis plan agreed with the FDA. The efficacy comparison was not against the trial's own sham arm.

How the FDA flipped in a year

In the fall of 2025, the 36-month readout thrilled the Huntington's community and investors. uniQure's share price more than tripled on the news of 75% slowing among 12 higher-dose patients. The FDA then pushed back unexpectedly, a key shift from prior communications. Agency staff did not view the results as adequate to support approval.

In late February 2026, then-FDA commissioner Marty Makary made CNBC comments that investors read as critical of AMT-130, and shares fell more than 30%. The following week, the FDA strongly recommended uniQure run another trial with a sham-surgery control arm. In an unusual move, an anonymous senior FDA official spoke to journalists criticizing AMT-130 and accusing uniQure of mischaracterizing talks. Many speculated the official was Vinay Prasad, who oversaw the office that regulates vaccines and gene therapies.

Makary resigned in mid-May 2026. Acting drug review director Tracy Beth Høeg was fired. Prasad had departed the FDA. On June 17, 2026, the FDA reversed course: it agreed three years of data could support an accelerated approval filing and dropped the sham-surgery demand. uniQure shares surged nearly 80% to about $48.

A May 2027 decision, and a confirmatory wait behind it

The main efficacy comparison was against the Enroll-HD observational external control, not a traditional placebo or sham arm. Differences between groups can influence results. Four-year follow-up data was hopeful but complex. BLA acceptance is a milestone, not an approval. The FDA could approve, request more information, or conclude the evidence is insufficient. The advisory committee meeting date is not yet confirmed.

If accelerated approval arrives, confirmation still sits years out. The confirmatory trial is randomized and standard-of-care-controlled, with approximately 200 patients in a 2:1 ratio of drug to standard of care and Total Functional Capacity as the primary endpoint at 36 months. Patient screening in the U.S. is planned to begin by the end of 2026. The FDA would be deciding on an external-control signal in 12 high-dose patients, long before that 200-patient study finishes screening and reads out.