uniQure files Huntington's gene therapy for FDA and UK approval

Overview

Updated Oct 1

uniQure reported four-year data from its Huntington's gene therapy trial on September 29. The results were mixed: the main composite measure showed 44% slower decline, short of statistical significance, while a functional-capacity measure showed 61% slower decline.

The approval filing, submitted September 2, rests on three-year data the FDA accepted as primary evidence after reversing an earlier rejection. An updated three-year analysis shows 80% slower progression on the composite scale. The FDA's filing-acceptance decision is expected in November, and uniQure's shares fell after the four-year data.

Why it matters

Approval would give Huntington's patients the first therapy that slows the disease, which today has no disease-modifying treatment.

Questions about this story

Free account needed to ask — your question is kept and asked for you right after sign-up. Answers are public.

No questions yet — be the first to ask.

Key Indicators

80%

Slowing of Huntington's progression, high-dose group at 3 years

Updated 36-month analysis on the composite cUHDRS scale versus an external control, statistically significant (p=0.005). This is the evidence base for the FDA and UK filings.

44%

cUHDRS slowing at 4 years

The main composite endpoint missed significance (p=0.144); a functional-capacity measure showed 61% slowing (p=0.008). Missing data in the external control partly explain the weaker 48-month readout.

75,000

People with Huntington's disease in the US, EU, and UK

The patient population a first disease-modifying therapy would target.

6 months

FDA review cycle if priority review is granted

Down from the standard 10-month review, after the 60-day filing acceptance period.

Voices

Curated perspectives — historical figures and your fellow readers.

Ever wondered what historical figures would say about today's headlines?

People Involved

Matt Kapusta

Chief executive officer, uniQure

Leading the company through regulatory review after mixed four-year data

Organizations Involved

uniQure N.V.

Gene therapy company

Sponsor of AMT-130; BLA and MAA under review, four-year data reported September 29, 2026

Amsterdam-based gene therapy company with US operations in Lexington, Massachusetts.

U.S. Food and Drug Administration

Federal regulatory agency

Reviewing the AMT-130 Biologics License Application

The US agency that decides whether new drugs and biologics can be marketed.

Medicines and Healthcare products Regulatory Agency

National regulatory agency

Reviewing the AMT-130 Marketing Authorisation Application

The UK regulator for medicines, medical devices, and blood products.

Timeline

June 2026 November 2026

4 events Latest: September 29th, 2026 · 1 week ago

Tap a bar to jump to that date

November 2026
FDA filing decision expected
Upcoming Regulatory

FDA has 60 days from submission to decide whether to accept the filing for review.
November 1st, 2026
September 2026
Four-year data reported; main endpoint misses significance
Latest Data release

Across 12 high-dose patients at 48 months, cUHDRS showed 44% slowing (p=0.144, not significant) and TFC showed 61% slowing (p=0.008). Updated 36-month data showed 80% cUHDRS slowing (p=0.005).
September 29th, 2026
uniQure files for FDA and UK approval
Regulatory

Company filed for accelerated US approval and UK approval, requesting priority review.
September 2nd, 2026
June 2026
FDA reverses course on AMT-130 data
Regulatory

FDA accepts three-year Phase I/II data as basis for accelerated-approval filing.
June 2026

Scenarios

FDA approves AMT-130 as first Huntington's gene therapy

Likely Resolves by Jun 1, 2027

Discussed by: uniQure's own guidance; PharmaDeviceNews notes approval would turn the program into a commercial launch

The FDA accepts the BLA after its 60-day review and grants the requested priority review, then issues an approval letter. The decision rests on whether the agency accepts the external-control comparison as sufficient evidence, with a post-approval confirmatory study now expected to compare against standard of care rather than a sham surgical procedure.

FDA issues Complete Response Letter, demands more data

Possible Resolves by Jun 1, 2027

Discussed by: PharmaDeviceNews notes the FDA can still conclude the external-control evidence is insufficient

The FDA accepts the filing but, after review, determines the Phase I/II external-control data do not provide robust enough evidence of effectiveness. It issues a Complete Response Letter requiring a randomized confirmatory trial before approval, sending the program back into clinical development for years.

FDA grants standard review, delaying the decision

Possible Resolves by Jan 1, 2027

Discussed by: uniQure's filing; priority review is requested but not guaranteed

The FDA accepts the BLA but denies the priority review request, setting a standard 10-month review cycle. The decision date moves to roughly mid-2027 or later, extending the period of regulatory uncertainty even if approval ultimately follows.

Historical Context

3 moments from history that rhyme with this story — and how they unfolded.

October 2012

Glybera, Europe's first gene therapy (2012)

uniQure, then Amsterdam Molecular Therapeutics, won European approval for Glybera, a gene therapy for the rare fat-metabolism disorder lipoprotein lipase deficiency. The one-time treatment carried a list price over $1 million.

Then

Only a small number of patients were ever treated, and the drug was withdrawn from the market in 2017.

Now

Showed that a gene therapy could be approved yet fail commercially if the patient pool is tiny and reimbursement is never secured.

Why this matters now

AMT-130 is another one-time, high-cost gene therapy for a small patient population. Approval would not resolve the access and coverage hurdles that sank Glybera.

March 2021

Roche's tominersen trial halted (2021)

Roche's tominersen, an antisense drug designed to lower huntingtin protein, was the leading disease-modifying candidate for Huntington's. The Phase 3 trial was halted in March 2021 after the higher-dose arm showed worsening outcomes.

Then

Roche scaled back the program; the setback shifted attention to other modalities, including gene therapy.

Now

Demonstrated how difficult it is to prove a therapy modifies Huntington's in a standard randomized trial.

Why this matters now

AMT-130 aims at the same target, huntingtin, but delivers gene silencing once through neurosurgery instead of repeated spinal injections.

May 2019

Zolgensma approval (2019)

The FDA approved Novartis's Zolgensma, a one-time gene therapy for spinal muscular atrophy, with a list price near $2.1 million. It became the first gene therapy for a neurological disease to reach the US market.

Then

Zolgensma saw rapid adoption but also years of reimbursement disputes and installment payment plans.

Now

Set the precedent that regulators would approve ultra-expensive, one-time gene therapies for rare neurological conditions.

Why this matters now

AMT-130 follows the Zolgensma template: a single administration, a high price, and reliance on specialized treatment centers and a long reimbursement tail.