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# Why uniQure's Huntington Filing Rests on Twelve Patients and Two FDA Reversals
- URL: https://bioweek.com/why-uniqures-huntington-filing-rests-on-twelve-patients-and-two-fda-reversals/
- Published: 2026-09-03T05:24:53.000Z
- Updated: 2026-09-04T05:15:06.000Z
- Description: uniQure asked FDA for accelerated approval of AMT-130 on a 12-patient, 36-month high-dose dataset, after the agency twice reversed itself on external-control evidence.
- Author: BioWeek
- Tags: Policy, Pipeline

uniQure N.V. on September 2, 2026 [submitted](https://www.benzinga.com/pressreleases/26/09/g61570082/uniqure-announces-submission-biologics-license-application-ifezuntirgene-inilparvovec-amt-130-huntin?ref=bioweek.com) a biologics license application to the U.S. Food and Drug Administration seeking accelerated approval of ifezuntirgene inilparvovec (AMT-130) for Huntington's disease, plus a marketing authorisation application to the U.K. MHRA. The company (NASDAQ: QURE) also [requested](https://www.benzinga.com/pressreleases/26/09/g61570082/uniqure-announces-submission-biologics-license-application-ifezuntirgene-inilparvovec-amt-130-huntin?ref=bioweek.com) priority review. If granted, the review cycle is six months after FDA's 60-day BLA filing review [period](https://www.benzinga.com/pressreleases/26/09/g61570082/uniqure-announces-submission-biologics-license-application-ifezuntirgene-inilparvovec-amt-130-huntin?ref=bioweek.com).

The package is a three-year Phase I/II analysis versus a propensity score-matched Enroll-HD external control, which the company says [demonstrated](https://www.benzinga.com/pressreleases/26/09/g61570082/uniqure-announces-submission-biologics-license-application-ifezuntirgene-inilparvovec-amt-130-huntin?ref=bioweek.com) a slowing of disease progression. The high-dose 36-month case is 12 [patients](https://www.sec.gov/Archives/edgar/data/1590560/000110465925092740/qure-20250924xex99d1.htm?ref=bioweek.com). By uniQure's updates, FDA reversed itself twice on whether that dataset can be primary evidence for accelerated approval.

### Twelve patients, 75 percent slowing, and a motor miss

On September 24, 2025, uniQure said high-dose AMT-130 [met](https://www.sec.gov/Archives/edgar/data/1590560/000110465925092740/qure-20250924xex99d1.htm?ref=bioweek.com) its primary endpoint: statistically significant 75 percent slowing at 36 months on cUHDRS versus a propensity score-matched external control (p=0.003), mean change -0.38 versus -1.52\. Total functional capacity [slowed](https://www.sec.gov/Archives/edgar/data/1590560/000110465925092740/qure-20250924xex99d1.htm?ref=bioweek.com) a statistically significant 60 percent (p=0.033), mean change -0.36 versus -0.88\. Mean cerebrospinal fluid neurofilament light was 8.2 percent below baseline at 36 months, per the same [release](https://www.sec.gov/Archives/edgar/data/1590560/000110465925092740/qure-20250924xex99d1.htm?ref=bioweek.com).

A prospectively defined statistical analysis plan aligned with FDA counted 29 treated patients, 17 high dose and 12 low dose, with 12 patients per dose at 36 months, according to the [filing](https://www.sec.gov/Archives/edgar/data/1590560/000110465925092740/qure-20250924xex99d1.htm?ref=bioweek.com). Enroll-HD supplied 940 high-dose and 626 low-dose matches, with a June 30, 2025 data [cutoff](https://www.sec.gov/Archives/edgar/data/1590560/000110465925092740/qure-20250924xex99d1.htm?ref=bioweek.com). Stroop Word Reading Test slowing was 113 percent (p=0.0021) in that [analysis](https://www.sec.gov/Archives/edgar/data/1590560/000110465925092740/qure-20250924xex99d1.htm?ref=bioweek.com). Symbol Digit Modalities Test slowing was 88 percent (p=0.057) and not statistically [significant](https://www.sec.gov/Archives/edgar/data/1590560/000110465925092740/qure-20250924xex99d1.htm?ref=bioweek.com). Total motor score slowing was 59 percent (p=0.1741) and not statistically [significant](https://www.sec.gov/Archives/edgar/data/1590560/000110465925092740/qure-20250924xex99d1.htm?ref=bioweek.com). uniQure said the pattern suggests a dose-dependent response. No new drug-related serious adverse events were reported since December 2022; procedure-related events [resolved](https://www.sec.gov/Archives/edgar/data/1590560/000110465925092740/qure-20250924xex99d1.htm?ref=bioweek.com). A first-quarter 2026 BLA plan later [slipped](https://www.benzinga.com/pressreleases/26/09/g61570082/uniqure-announces-submission-biologics-license-application-ifezuntirgene-inilparvovec-amt-130-huntin?ref=bioweek.com). Four-year data are due before the current third quarter [ends](https://www.benzinga.com/pressreleases/26/09/g61570082/uniqure-announces-submission-biologics-license-application-ifezuntirgene-inilparvovec-amt-130-huntin?ref=bioweek.com).

### A striatal infusion and a sham that never entered the skull

AMT-130 is a miQURE miRNA designed to silence huntingtin and a potentially highly toxic exon 1 fragment, given once by MRI-guided, convection-enhanced stereotactic delivery into the caudate and putamen, the company [said](https://www.benzinga.com/pressreleases/26/09/g61570082/uniqure-announces-submission-biologics-license-application-ifezuntirgene-inilparvovec-amt-130-huntin?ref=bioweek.com). The U.S. randomized study enrolled 26 patients: 6 low dose at 6x10^12 genome copies, 10 high dose at 6x10^13 genome copies, and 10 sham, with four crossovers after about 12 months, per [NCT04120493](https://clinicaltrials.gov/study/NCT04120493?ref=bioweek.com). Sham used skin incisions only, with no burr holes and no intrastriatal [injections](https://clinicaltrials.gov/study/NCT04120493?ref=bioweek.com). Specified cohorts required early manifest disease, total functional capacity 9 to 13, ages 25 to 65, and at least 40 CAG [repeats](https://clinicaltrials.gov/study/NCT04120493?ref=bioweek.com).

uniQure described a European open-label study of 13 patients; ClinicalTrials.gov lists [enrollment](https://clinicaltrials.gov/study/NCT05243017?ref=bioweek.com) of 14\. A third cohort of 12 patients received both doses plus immunosuppression, the company [said](https://www.benzinga.com/pressreleases/26/09/g61570082/uniqure-announces-submission-biologics-license-application-ifezuntirgene-inilparvovec-amt-130-huntin?ref=bioweek.com). The European protocol lists dexamethasone, sirolimus, and rituximab as that [regimen](https://clinicaltrials.gov/study/NCT05243017?ref=bioweek.com). A fourth U.S. cohort enrolled six high-dose patients with lower striatal [volumes](https://uniqure.gcs-web.com/news-releases/news-release-details/uniqure-announces-plan-bla-submission-amt-130-huntingtons?ref=bioweek.com). Huntington's is an autosomal-dominant neurodegenerative disorder of chorea, behavioral change, and cognitive decline from a CAG expansion in huntingtin. About 75,000 people have the disease in the United States, the European Union, and the United Kingdom combined, the company [estimates](https://www.benzinga.com/pressreleases/26/09/g61570082/uniqure-announces-submission-biologics-license-application-ifezuntirgene-inilparvovec-amt-130-huntin?ref=bioweek.com). There are no approved therapies to delay onset or slow progression, uniQure [says](https://www.benzinga.com/pressreleases/26/09/g61570082/uniqure-announces-submission-biologics-license-application-ifezuntirgene-inilparvovec-amt-130-huntin?ref=bioweek.com).

### Yes, then no, then yes

AMT-130 is the first investigational Huntington's therapy to receive Breakthrough Therapy and RMAT designations and also holds Fast Track, uniQure [stated](https://www.benzinga.com/pressreleases/26/09/g61570082/uniqure-announces-submission-biologics-license-application-ifezuntirgene-inilparvovec-amt-130-huntin?ref=bioweek.com). Breakthrough Therapy came in April 2025 on Phase I/II data versus external [controls](https://uniqure.gcs-web.com/news-releases/news-release-details/uniqure-provides-regulatory-update-amt-130-huntingtons-disease-0?ref=bioweek.com). RMAT came in May 2024, the first such designation in Huntington's disease, according to a later [update](https://uniqure.gcs-web.com/news-releases/news-release-details/uniqure-announces-plan-bla-submission-amt-130-huntingtons?ref=bioweek.com).

On November 3, 2025, uniQure said it believed FDA no longer [agreed](https://uniqure.gcs-web.com/news-releases/news-release-details/uniqure-provides-regulatory-update-amt-130-huntingtons-disease-0?ref=bioweek.com) that Phase I/II data versus an external control may be adequate as primary evidence for a BLA. The company called it a key shift from November 2024 FDA guidance that Phase I/II versus a natural history external control may serve as the primary basis for a BLA under accelerated [approval](https://uniqure.gcs-web.com/news-releases/news-release-details/uniqure-provides-regulatory-update-amt-130-huntingtons-disease-0?ref=bioweek.com).

On June 17, 2026, after another Type B meeting, uniQure said FDA found the three-year Phase I/II analysis [acceptable](https://uniqure.gcs-web.com/news-releases/news-release-details/uniqure-announces-plan-bla-submission-amt-130-huntingtons?ref=bioweek.com) as the primary basis of a BLA for accelerated approval. FDA sought to align on confirmatory study design before submission, including a concurrent standard-of-care control instead of a sham procedure. uniQure committed to a confirmatory study without delay and planned a third-quarter 2026 [BLA](https://uniqure.gcs-web.com/news-releases/news-release-details/uniqure-announces-plan-bla-submission-amt-130-huntingtons?ref=bioweek.com). The September 2 submissions meet that [window](https://www.benzinga.com/pressreleases/26/09/g61570082/uniqure-announces-submission-biologics-license-application-ifezuntirgene-inilparvovec-amt-130-huntin?ref=bioweek.com).

### What the application is asking FDA to accept

Accelerated approval would rest on 12 high-dose patients at 36 months against 940 Enroll-HD matches, with CSF NfL below baseline, while total motor score did not separate statistically, as the 2025 [topline](https://www.sec.gov/Archives/edgar/data/1590560/000110465925092740/qure-20250924xex99d1.htm?ref=bioweek.com) showed. The sham comparison was time-limited, and sham patients never received burr holes or striatal injections, so it cannot fully isolate surgery from vector. FDA asked to align a confirmatory trial before filing, including a standard-of-care control. The September 2 [announcement](https://www.benzinga.com/pressreleases/26/09/g61570082/uniqure-announces-submission-biologics-license-application-ifezuntirgene-inilparvovec-amt-130-huntin?ref=bioweek.com) does not say that alignment was finished. The filing asks whether a one-time striatal AAV gene therapy can receive accelerated approval on external-control evidence after FDA twice changed its position, for a disease with no approved therapy to delay onset or slow progression.