UniQure AMT-130 FDA Rebuff Forces New Phase 3
UniQure AMT-130 FDA decision requires a randomized sham-controlled Phase 3, blocking a BLA path and delaying the Huntington's gene therapy timeline.
KEY TAKEAWAYS
- FDA rejected a BLA path and demanded a randomized, double-blind, sham-surgery Phase 3 as primary evidence.
- Reviewers found the Phase 1/2 dataset insufficient and detected no benefit versus sham at 12 months.
- UniQure will request a Type B meeting in Q2 2026 and update Phase 1/2 with a four-year analysis.
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UniQure’s (QURE) attempt to file a biologics license application (BLA) for AMT-130 encountered a regulatory setback after March 2, 2026 meeting minutes revealed FDA reviewers found the Phase 1/2 data insufficient. The agency now requires a randomized, double-blind, sham-surgery controlled Phase 3 trial, extending the program’s timeline.
FDA Demands Sham-Controlled Phase 3 Trial
The FDA rejected UniQure’s plan to rely on Phase 1/2 data compared with an external natural-history control as primary evidence of effectiveness. Reviewers concluded the dataset was inadequate and found no therapeutic benefit compared with sham surgery at the 12-month assessment. The agency withdrew its prior agreement allowing use of an external control, reflecting a broader trend of limiting reliance on external data in rare-disease programs.
AMT-130 Clinical Data and Delivery Method
AMT-130 is a one-time gene therapy using an AAV5 vector to silence the mutant huntingtin gene in Huntington’s disease. It is delivered via intracranial injection through burr holes drilled in the skull. The trial’s sham procedure involved superficial drilling and anesthesia without injection. The Phase 1/2 study included 10 sham controls.
UniQure’s high-dose cohort showed a 75.0% reduction in disease progression compared with the Enroll-HD external control at three years.
UniQure’s Next Steps and Timeline
On November 3, 2025, UniQure announced the FDA had reversed a prior written agreement that permitted use of the external natural-history database, which includes more than 30,000 participants over 14 years. The agency held a Type A meeting on January 30, 2026, concluding the Phase 1/2 data were insufficient. On March 5, 2026, senior FDA and Health and Human Services officials publicly criticized the therapy and questioned the company’s claims.
UniQure plans to request a Type B meeting in the second quarter of 2026 to discuss Phase 3 design and will update its Phase 1/2 dataset with a four-year analysis in the third quarter. The company intends to seek regulatory flexibility while developing a prospectively randomized trial. These steps will determine whether UniQure can regain a faster path to approval or must complete the sham-controlled study now required by the FDA.
