UniQure and FDA No Longer in Alignment on Approval Pathway for AMT-130

In a very brief press release from uniQure on November 3, 2025 we learned that the company is no longer aligned with the FDA on moving their drug AMT-130 forward. Just a few weeks ago, positive news from their ongoing clinical trials took the world by storm. Their goal was to use those data to apply for a Biologics Licensing Application (BLA) to market AMT-130 as a disease modifying drug for Huntington’s disease (HD). However, that goal was reliant on remaining aligned with the FDA. So, what do we know? What does this mean for AMT-130? And where do we go from here?

What We Know

A BLA, or Biologics Licensing Application, is the formal dossier of information that a company uses to request permission to market a biologic, which is a therapy created from living organisms, like proteins, cells, or genetic material. AMT-130 is considered a biologic because it uses (harmless) virus to deliver genetic material – the instructions needed to lower huntingtin protein levels in cells in the brain. 

UniQure had planned to submit their BLA to the FDA in just a few months, in early 2026. And until now, they were aligned with the FDA for submitting this application, with the most recent update of alignment in June of 2025. So what happened in the last 5 months to change that decision?

Unfortunately, we only have a 30,000 foot view of the update from uniQure’s meeting with the FDA, as minutes from that meeting haven’t been released or given to uniQure yet. The press release we’ve received from the company states that, “uniQure believes that the FDA currently no longer agrees that data from the Phase I/II studies of AMT-130 in comparison to an external control, as per the prespecified protocols and statistical analysis plans shared with the FDA in advance of the analyses, may be adequate to provide the primary evidence in support of a BLA submission.”

So it seems the major issue the agency currently has with the data they’ve received is around the use of an external control comparator group. This is a major shift from the latest update we had from uniQure this summer, which followed similar messaging dating back to November 2024, when they first shared that they maintained alignment with the FDA on clinical endpoints needed for a successful BLA application. 

Why Does The Control Group Matter?

Many clinical trials test a drug against a placebo group, which is a group of participants that are given a mock treatment, like a sugar pill or, in this case, a mock surgery. This type of placebo group is considered a rigorous way for researchers to test if the effects they may be seeing are due to the drug, or are psychosomatic effects that hope for an effective treatment could bring on. The mind is incredibly powerful! And sometimes just thinking you’re receiving a treatment can have positive biological effects. 

Initially, the AMT-130 clinical trials were tested against a placebo group – a small group of people who were given a mock surgery. They were followed for the first 12 months of the study, and after that they were given the option of receiving the drug. However, because of the progressive nature of HD and because gene therapy studies are quite long, some of those people no longer fit within the inclusion criteria used for the trial. 

The reason for the change of heart by the agency is not currently clear. However, it makes the timeline for advancing AMT-130 less clear, with additional uncertainty as the US government shutdown continues. 

Because of that, moving forward the study was designed to compare people who received AMT-130 against an “external control group”, who were made up of people who participated in Enroll-HD. 

While an external control group is a less rigorous way to test a drug, some people consider it a more ethical way to test gene therapy drugs that are in early clinical stages. While these natural history comparator groups can give us an idea if a drug is meeting certain metrics, particularly early on, they may not be robust enough to provide conclusive evidence that a gene therapy may be effective. And this seems to be the crux of what is driving the current misalignment with the FDA, despite their previous agreement in this approach. 

What Does This Mean For AMT-130?

The decision by the FDA to not agree that an external control group can be used to apply for a BLA doesn’t change the data. It simply means that the FDA would want to see more data, possibly from a trial designed with a placebo control group, before moving forward with a BLA for AMT-130. 

We know this will come as a massive disappointment for many in the HD community, particularly since this decision seems a bit confusing. While a Breakthrough Therapy designation and a Regenerative Medicines Advanced Therapy (RMAT) designation was given to AMT-130 based on the use of a external control comparator group, this no longer appears to be sufficient for the agency.

The reason for the change of heart by the agency is not currently clear. However, it makes the timeline for advancing AMT-130 less clear, with additional uncertainty as the US government shutdown continues. 

AMT-130 Will Continue To Advance

Despite this disappointing news, this doesn’t mean that this is the end of the road for AMT-130 and it doesn’t change what the data show. The data still indicate that AMT-130 appears to be largely safe and well tolerated and against an external control group it seems to be having a meaningful effect on HD progression. That continues to be the strongest evidence we have thus far that modifying the disease course of HD might be possible. This is what Dr. Ed Wild calls a “save point” in the story of HD drug development – a point of progress that the community can return to, learn from, and build upon, even when we encounter unexpected challenges along the way.

However, this could change the timeline for when AMT-130 could be expected to be available for the HD community. Their recent announcement states that, “uniQure expects to receive final minutes within 30 days of the meeting and plans to urgently interact with the FDA to find a path forward for the timely accelerated approval of AMT-130”. So we expect that uniQure will continue to forge forward in advancing AMT-130 for the HD community in the US. 

Additionally, uniQure shared that they’re also working with regulatory agencies in Europe and the UK. And an advancement in one market would be an advancement for HD globally. Not only for the HD community members who live in those countries, but also because approval in other countries could ease the path to approval in others. 

This is what Dr. Ed Wild calls a “save point” in the story of HD drug development – a point of progress that the community can return to, learn from, and build upon, even when we encounter unexpected challenges along the way.

We Push Forward – Together

This news will feel like a failure to some, particularly those who may have been swept up in the grandeur of the recent headlines about a “cure” or “treatment” for HD being found. But science always progresses incrementally, not in massive leaps. Sometimes that incremental progression isn’t linear, which is what we’re seeing now with the misalignment between uniQure and the FDA. 

What’s important is that nothing has fundamentally changed about what we know. The data around AMT-130 remain the same. It continues to be safe and well tolerated and the data suggest the drug could modify disease progression. Previous trial disappointments for the HD community involved safety or efficacy issues, which is not what is happening here. This disappointment comes from a misalignment between the drug maker and a single regulatory agency about what may be needed to progress the drug to the next step. 

It’s currently unclear why the FDA no longer agrees that an external comparator group is sufficient after they determined that it was just 5 months ago. However, given the dedication of uniQure to advancing AMT-130, their stated plan to continue to interact with the FDA urgently, and ongoing work with regulatory agencies in Europe and the UK, this is merely a sidestep in the continued advancement of a disease modifying drug for HD.

Summary

• UniQure Update: In a November 3, 2025 press release, uniQure announced it is no longer aligned with the FDA on how to advance its gene therapy AMT-130 for Huntington’s disease.
• Key Issue: The FDA now disagrees with using an external control group (from Enroll-HD data) as the main comparison for efficacy in a Biologics Licensing Application (BLA).
• Background: UniQure had been aligned with the FDA as recently as June 2025, with plans to file a BLA in early 2026. This shift changes that trajectory.
• Why It Matters: External controls can be less rigorous than placebo groups, though some may consider them more ethical for invasive, one-time treatments like gene therapy. The FDA now appears to want more robust, controlled data.
• Impact: The data themselves haven’t changed. AMT-130 still appears safe, well tolerated, and potentially disease-modifying, but the approval timeline is now uncertain.
• Next Steps: UniQure will receive meeting minutes within 30 days and plans to “urgently” re-engage with the FDA to find a new approval path, while continuing work with regulators in Europe and the UK.
• Big Picture: This is a regulatory misalignment, not a scientific setback. It reflects the slow, iterative nature of drug development. Progress continues, just on a different timetable.