uniQure N.V. (Nasdaq: QURE) has submitted a Biologics License Application (BLA) to the US FDA seeking accelerated approval of ifezuntirgene inilparvovec (AMT-130), an AAV5-based gene therapy designed to slow the progression of Huntington's disease — a condition for which no approved disease-modifying treatment currently exists. Lexington, Massachusetts-based uniQure simultaneously filed a Marketing Authorisation Application (MAA) with the UK Medicines and Healthcare products Regulatory Agency (MHRA). The company has requested priority review for the US application, which, if granted, would shorten the FDA review cycle to six months following the agency's 60-day filing review period.
In November 2025, the FDA communicated that it no longer agreed Phase I/II data compared to an external control were adequate to support a BLA, triggering a share price collapse of more than 49%. Following a Type A meeting in January 2026 that reaffirmed that position, uniQure pursued a Type B meeting, which ultimately produced a materially different outcome: the FDA indicated in June 2026 that three-year Phase I/II data could serve as the primary basis for an accelerated approval application, contingent on alignment over a required confirmatory study design.
The evidentiary package rests on two multi-center Phase I/II studies (NCT04120493, NCT05243017). In the US randomized study, 26 patients with early manifest Huntington's disease received either ifezuntirgene inilparvovec (six low dose, ten high dose) or a sham procedure, with four control patients subsequently crossing over to treatment. The European open-label study enrolled 13 additional patients. Three-year results showed a statistically significant 75% slowing of disease progression at the high dose as measured by the composite Unified Huntington's Disease Rating Scale versus a propensity score-matched external control derived from the Enroll-HD natural history database (p=0.003), with a key secondary endpoint of Total Functional Capacity demonstrating a statistically significant 60% slowing (p=0.033). A mean reduction of 8.2% from baseline in cerebrospinal neurofilament light protein was also reported at 36 months in the high-dose group. The therapy was reported to be generally well-tolerated, with no new drug-related serious adverse events since December 2022.
Ifezuntirgene inilparvovec delivers a proprietary microRNA via an AAV5 vector through MRI-guided, convection-enhanced stereotactic neurosurgical administration directly into the striatum. The therapy is designed to lower huntingtin expression and thereby reduce production of the toxic mutant huntingtin protein that drives Huntington's disease pathology. AMT-130 holds Breakthrough Therapy, Regenerative Medicine Advanced Therapy (RMAT), and Fast Track designations from the US FDA, with uniQure describing the RMAT designation as the first granted for Huntington's disease. The company said it intends to present four-year data from the ongoing Phase I/II studies before the end of Q3 2026.