FDA Reversal and Accelerated Approval Pathway Secured

uniQure (NASDAQ: QURE)'s gene therapy, AMT-130, for Huntington's Disease, has secured a pathway for a Biologics License Application (BLA) filing with the FDA for accelerated approval. In November 2025, the FDA stated that the Phase I/II data and external control comparison were insufficient for approval and requested an additional sham surgery control trial. However, in June 2026, during a Type B meeting, the FDA completely reversed this position. Instead of the ethically controversial sham surgery (performing actual brain surgery without administering the drug), an agreement was reached to apply a standard-of-care, concurrent control group design to the confirmatory study. The BLA submission is scheduled for the third quarter of 2026 (July-September).

Phase I/II 36-Month Key Clinical Data

In the NCT04120493 trial, patients in the high-dose group (12 patients) of AMT-130 were followed for 36 months, and the results showed that disease progression, based on the composite unified Huntington's Disease rating scale (cUHDRS), was slowed by 75% compared to the propensity score-matched external control group. Cerebrospinal fluid neurofilament light chain (CSF NfL) decreased by 8.2% compared to baseline, suggesting inhibition of nerve damage, and the pre-specified primary endpoint was met. No new serious drug-related adverse events have been reported since December 2022, indicating a favorable safety profile. AMT-130 is a one-time, surgically administered gene therapy that delivers an artificial microRNA (miHTT) via an AAV5 vector to suppress the production of huntingtin protein.

FDA Leadership Change and Increased Regulatory Flexibility

A major change in FDA leadership is behind this reversal. Marty Makary, Director, resigned in mid-May 2026, and Vinay Prasad, of the gene therapy office, retired in April. Tracy Beth Høeg, the acting head of the new drug review division, was also dismissed. Under the new leadership, the FDA is taking a more pragmatic approach, and the industry interprets the withdrawal of the ethically controversial sham surgery requirement as a result. The Breakthrough Therapy Designation granted to AMT-130 in April 2025 appears to have had a positive impact on regulatory discussions.

Competitive Pipeline and Market Landscape

AMT-130 is the most advanced drug in the pipeline of disease-modifying therapies (DMTs) for Huntington's Disease. PTC Therapeutics/Novartis (PF)'s PTC518 (votoplam, oral small molecule, HTT-lowering agent) is in Phase II, and Novartis has entered into a licensing agreement worth up to USD 2.9 billion. Wave Life Sciences (WVE)'s WVE-003 (ASO) demonstrated a 46% reduction in mutant huntingtin (mHTT) in the Phase Ib/IIa SELECT-HD trial, and Roche (RHHBY)/Ionis (IONS)'s tominersen is being re-evaluated in a lower-dose Phase II trial after a Phase III failure (with a target submission date of 2028 or later). The global market for Huntington's Disease therapeutics is estimated at approximately USD 800 million to USD 1.4 billion in 2025 and is projected to grow at a CAGR of 15% to 18% by 2030.

Stock Reaction and Re-evaluation of Valuation

On the day of the announcement (June 17, 2026), uniQure's stock price soared approximately 80%, reaching approximately USD 48 per share, and the market capitalization increased to approximately USD 3 billion. Upon approval, AMT-130 will be the first disease-modifying gene therapy for Huntington's Disease, and its one-time administration offers a differentiated value proposition compared to competing ASO and small molecule drugs that require repeated administration. However, the FDA's final agreement on the confirmatory study design, cGMP manufacturing scale-up, and the establishment of a commercial infrastructure specializing in rare diseases remain key hurdles.