uniQure’s AMT-130 gene therapy for Huntington’s disease hits FDA roadblock: Phase I/II data insufficient for BLA; Phase III trial urged. Company seeks Type B meeting in Q2 2026 for next steps in HD treatment race.
Written By: Marka Sheshi, PharmD
Reviewed By: Pharmacally Editorial Team
uniQure N.V. a pioneer in gene therapy for severe neurological disorders, disclosed final minutes from a critical Type A meeting with the U.S. Food and Drug Administration (FDA) on January 30, 2026. The discussion centered on AMT-130, uniQure’s investigational one-time gene therapy designed to slow Huntington’s disease (HD) progression by lowering levels of the toxic huntingtin protein through RNA interference.
The FDA delivered a clear setback: it rejected the notion that Phase I/II trial data compared against external controls could serve as primary evidence of effectiveness for a marketing application (BLA). Instead, regulators insisted on a rigorous Phase III trial: prospective, randomized, double-blind, and sham surgery controlled. This gold-standard design minimizes biases inherent in smaller studies or historical comparisons, ensuring robust proof of clinical benefit in HD, a devastating, inherited neurodegenerative disease with no approved disease-modifying therapies.
uniQure CEO Matt Kapusta expressed disappointment but resolve. “While we did not reach alignment on a submission pathway based on the Phase I/II data, we believe the totality and durability of our data warrant continued substantive dialogue regarding how the FDA’s stated commitment to regulatory flexibility may be appropriately applied in this setting,” he said. The company plans a Type B meeting in Q2 2026 to explore Phase III designs, signaling ongoing collaboration rather than abandonment.
This stance reflects FDA priorities for gene therapies in rare diseases. AMT-130’s early data showed promising durability up to three years of huntingtin reduction and motor function stabilization in open-label trials, but external controls couldn’t fully address placebo effects or sham surgery confounders common in CNS trials. uniQure’s next steps could leverage FDA incentives like RMAT designation (already granted) or accelerated approval if Phase III endpoints align with unmet needs.
For the HD community, affecting 30,000 in the U.S., this underscores the tension between urgency and evidence. uniQure reaffirmed commitment: “We remain committed to standing with patients and their families as we advance this potentially transformative therapy for a community in need.”
Reference
uniQure Provides Regulatory Update on AMT-130 for Huntington’s Disease, 02 March 2026, https://www.uniqure.com/investors-media/press-releases
National Center for Biotechnology Information (US). Genes and Disease [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 1998-. Huntington disease. Available from: https://www.ncbi.nlm.nih.gov/books/NBK22226/
Safety and Efficacy of AMT-130 in European Adults With Early Manifest Huntington’s Disease, ClinicalTrials.gov ID NCT05243017, https://clinicaltrials.gov/study/NCT0524301
Safety and Proof-of-Concept (POC) Study With AMT-130 in Adults With Early Manifest Huntington’s Disease, ClinicalTrials.gov ID NCT04120493, https://clinicaltrials.gov/study/NCT04120493
About Writer
Marka Sheshi | Doctor of Pharmacy
Driven by a deep commitment to clinical excellence, research integrity, and impactful medical writing. With a strong foundation in pharmacotherapy and patient safety, specializes in transforming complex scientific evidence into authoritative, publication-ready content. Passionate about advancing healthcare through precise, evidence-based communication that informs practice, strengthens research visibility, and improves patient outcomes.