FDA Agrees AMT-130 Phase I/II Data Can Anchor BLA for Huntington's Disease Under Accelerated Approval — Sham-Surgery Phase 3 No Longer Required

FDA has agreed that three years of Phase I/II data from the gene therapy AMT-130 can support a Biologics License Application under Accelerated Approval for Huntington’s disease — a significant regulatory shift announced June 17, 2026 following a Type B meeting between uniQure and the agency. The agreement also removes a demand for a sham-surgery-controlled confirmatory trial, replacing it with an accepted standard-of-care control arm. uniQure has announced a BLA submission planned for Q3 2026. No application has yet been filed, and no approval has been granted.

What FDA agreed to — and what it did not

The Type B meeting outcome is a pre-submission agreement on the regulatory pathway, not an approval decision. Under Accelerated Approval, FDA may grant conditional marketing authorization based on a surrogate or intermediate endpoint reasonably likely to predict clinical benefit, with a requirement to conduct a confirmatory trial verifying that benefit. The June 2026 agreement means FDA has concluded that the Phase I/II dataset is sufficient to anchor a BLA submission, not that the agency has evaluated or will approve that BLA.

The distinction matters. The news release announcing the outcome uses language about “plan for BLA submission” — not an approval, not an advisory committee date, not a PDUFA date. Those steps remain ahead.

A regulatory about-face — twice

What makes this outcome notable is its position as the second reversal in seven months on the same core question: what kind of Phase 3 confirmatory study FDA would require if AMT-130 receives accelerated approval.

In November 2025, FDA informed uniQure that any confirmatory trial must include a sham-surgery control arm — a design requiring that some patients with Huntington’s disease undergo a simulated cranial procedure without receiving the gene therapy. The agency reaffirmed that demand in March 2026. Both positions generated substantial controversy among HD patient advocates and neurology researchers who argued that sham surgery in this population posed serious ethical and practical barriers to enrollment.

By June 2026, FDA reversed course. The Type B meeting outcome confirms that the confirmatory trial may use a standard-of-care comparator in place of a sham-surgery control — a design change that meaningfully lowers the barrier to conducting that study.

The regulatory flip from the November 2025 and March 2026 positions to the June 2026 position represents a substantial shift in FDA’s requirements for this program.

The drug and the designations

AMT-130 is a gene therapy delivered via a single stereotactic intracranial injection. It uses an adeno-associated virus serotype 5 (AAV5) vector to deliver a microRNA construct that silences mutant huntingtin protein expression in the striatum. Huntington’s disease is caused by a CAG repeat expansion in the HTT gene, leading to progressive neurodegeneration and death; there is currently no approved disease-modifying therapy.

FDA has granted AMT-130 four designations: Breakthrough Therapy status (April 2025), Regenerative Medicine Advanced Therapy (RMAT) designation — the first RMAT designation for a Huntington’s disease therapy, granted in 2024 — as well as Fast Track and Orphan Drug designations.

The Phase I/II evidence base

The U.S. trial (NCT04120493) enrolled 43 patients across four cohorts. The initial randomized phase included a low-dose cohort and a high-dose cohort, each randomized against a sham-surgery control arm. Subsequent enrollment added Cohort 3 (an expansion/extension cohort) and Cohort 4 (an open-label high-dose cohort in patients with low striatal volume). The European Phase Ib/2 study (NCT05243017) enrolled an additional 14 patients.

The efficacy and safety data supporting the BLA pathway were reported by uniQure in a September 24, 2025 press release and have not yet been independently peer-reviewed in full. At a September 2025 data cutoff, the company reported the following company-reported figures (Phase I/II data; not peer-reviewed):

In the 12 high-dose patients who reached 36-month follow-up (of 17 treated in the high-dose cohort), mean change from baseline on the composite Unified Huntington’s Disease Rating Scale (cUHDRS) was −0.38, compared with −1.52 in 940 Enroll-HD matched external controls (P=.003). The company described this as representing approximately 75% slowing of disease progression relative to the external control group. (Company-reported; Phase I/II data not yet peer-reviewed in full.)

The cUHDRS comparison uses an external, non-randomized control — the 940 Enroll-HD matched controls are a registry-derived comparator, not patients who were concurrently randomized to a placebo or sham procedure. The 12 patients at 36 months are a subset of the 17 treated in the high-dose cohort; the remaining high-dose patients had not yet reached the 36-month follow-up window at the September 2025 data cutoff.

CSF neurofilament light chain (NfL), a biomarker of neuroaxonal injury used as a secondary measure, decreased 8.2% from baseline at 36 months in the high-dose group (company-reported; not peer-reviewed). No new drug-related serious adverse events have been reported since December 2022 (company-reported).

What the BLA pathway does not resolve

Accelerated Approval under this pathway would be conditional. The confirmatory trial — now accepted to use a standard-of-care control — must demonstrate clinical benefit on a validated endpoint to convert any accelerated approval to full approval. The design, enrollment, and timeline for that confirmatory study have not been publicly specified as of this writing.

The BLA submission itself remains ahead. After filing, FDA will conduct a filing review before accepting the application, assign a PDUFA action date, and may convene an advisory committee. None of those steps has occurred.

For a disease that has had no approved disease-modifying therapy, the pathway agreement is a meaningful development. But the distance between a Type B meeting outcome and an approval is substantial, and each intervening step carries its own review standard.

All efficacy and safety figures from uniQure’s September 2025 and June 2026 press releases are company-reported and have not been independently peer-reviewed. This article will be updated if peer-reviewed data or a formal BLA acceptance are announced.