uniQure gene therapy slows Huntington’s progression, but investors aren’t convinced

uniQure has reported additional data from the ongoing phase 1/2 studies of ifezuntirgene inilparvovec (AMT-130), showing a 44% slowing of Huntington’s disease progression compared with an external control, but the result did not reach statistical significance, raising questions about the gene therapy’s path forward.

The new 36-month analysis includes 15 high-dose and 12 low-dose patients, with three additional high-dose patients having reached that timepoint since the September 2025 analysis. The 48-month analysis includes 12 patients at each dose.

Among 12 high-dose patients at 48 months, the therapy slowed progression by 44% on the primary composite Unified Huntington’s Disease Rating Scale (cUHDRS), although the result was not statistically significant, while the Total Functional Capacity (TFC) measure showed a 61% slowing. At 36 months, data from 15 high-dose patients showed an 80% slowing on cUHDRS and 67% on TFC, both with nominally significant p values.

uniQure says the 48-month results may underestimate the treatment effect because of missing data and survivor bias in the external control group. The market didn’t agree, with uniQure stock crashing more than 39% this morning.

AMT-130 consists of an AAV5 vector carrying an artificial micro-RNA specifically tailored to silence the huntingtin gene, leveraging the company’s proprietary miQURE silencing technology. The therapeutic goal is to inhibit the production of the mutant protein. If approved, it will be the first genetic treatment for Huntington’s disease.

uniQure submitted its BLA to the FDA for the accelerated approval of AMT-130 in early September. The submission came after much back and forth between uniQure and the agency.The trouble began at a pre-BLA meeting in October 2025, when the agency said it did not consider data from the phase 1/2 studies of AMT-130 sufficient to support a BLA. In February 2026, FDA Commissioner Marty Makary appeared to reference and criticize the therapy during an interview with CNBC, saying, “There was a product where the researchers drilled a burr hole, literally a hole, in people’s skulls. At the end of the randomization period, it was found no benefit, and yet this is one of the drugs that we were pressured to approve.”

Final Type A meeting minutes released in March confirmed the FDA’s position and strongly recommended a prospective, randomized, double-blind, sham surgery-controlled study. Such a trial would be particularly challenging for AMT-130, which is administered once directly into the brain through a complex neurosurgical procedure. The FDA reversed course in June, following the March resignation of CBER director Vinay Prasad and Makary’s May resignation, agreeing that three-year data from the phase 1/2 study could serve as the primary basis for a BLA.