The road ahead for uniQure: FDA says more data needed for AMT-130 gene therapy

Article: On March 2, 2026, uniQure announced that it has received final meeting minutes from the U.S. Food and Drug Administration (FDA) following a Type A meeting held on January 30, 2026 to discuss AMT-130, its investigational gene therapy for Huntington’s disease (HD). uniQure says they were told by the FDA that their current data are insufficient for the FDA to approve AMT-130. This is disappointing news for the HD community. 

What is AMT-130?

AMT-130 is a gene therapy designed to lower levels of the huntingtin protein in the brain. It uses a harmless virus package, called an adeno-associated virus (AAV), to contain microRNA – genetic instructions to lower huntingtin levels. The therapy is delivered directly into the striatum, the deep part of the brain most impacted in HD, using brain surgery. By lowering huntingtin levels, uniQure, like many other companies developing drugs for HD, hope to slow or halt signs and symptoms of HD.

uniQure has been developing AMT-130 for several years, and we’ve been following the story since the beginning, as it progressed from animal studies through to the clinic:

• Promising results from animal models, covered in April, 2021
• The announcement of the clinical trial, covered in July, 2021
• 12 month safety data, covered in July, 2022
• A short pause in the trial, covered in August, 2022
• The trial resumes, covered in November, 2022
• A promising safety profile, covered in December, 2023
• AMT-130’s potential to slow clinical progression, covered in July, 2024
• Previous alignment with the FDA, covered in December, 2024
• Hopeful for accelerated approval, covered in June, 2025
• Positive trial results announced, covered in September, 2025
• Digging into what the trial data show, covered in October, 2025
• No longer aligned with FDA, covered in November, 2025
• The community response, covered in December, 2025
• Securing a Type A meeting with the FDA, covered in January, 2026

Earlier studies were designed to assess safety, while also collecting extra data for different  measures like biomarkers (e.g., NfL, a readout of brain health) and clinical outcomes (e.g., cUHDRS, a collection of clinical metrics) over time. While the trial wasn’t specifically designed to use the measurements to determine if AMT-130 is effective against HD, it could serve as a proof-of-concept, giving them a hint at if the drug could potentially do the job they hoped it would.

With these small proof-of-concept assessments, uniQure has previously shared data from their Phase 1/2 clinical trial suggesting that lowering of the huntingtin protein with AMT-130 seems to track with improved clinical measures compared with external control datasets. However, for AMT-130 to be approved, regulators must be convinced that this therapy provides clear clinical benefit to people living with HD.

What did the FDA say?

In November of 2025, the FDA stated that it does not agree that uniQure’s data from the Phase 1/2 clinical study are sufficient evidence that AMT-130 offers clinical benefit for people with HD, and thus cannot support a marketing application for AMT-130. In other words, based on the data collected so far, the FDA does not believe there is enough evidence to approve the therapy.

To reach this decision, the FDA looked at the entire dossier of information uniQure has amassed on AMT-130 thus far. This included the initial 12 months of the study where participants treated with AMT-130 were compared to people treated with a sham surgery. While there wasn’t a statistical difference between people treated with AMT-130 and those with sham at 12 months, this was a very small group of people. Additionally, this part of the study was designed to look at the safety of the drug, not how effective it was at treating signs and symptoms of HD.

In their recent meeting minutes, uniQure stated that the FDA disagreed with the external control group that uniQure used to benchmark how effective AMT-130 was in their trial. This was confusing for the community as previously, the press releases from uniQure had indicated that they were aligned with the FDA on this approach. 

In uniQure’s most recent press release on March 2, 2026, the relayed that the agency strongly recommended that uniQure conduct a new trial to robustly demonstrate that AMT-130 is effective. They suggest that uniQure alter their trial design, the biggest change of which would be that participants would be randomly assigned to one of two groups – one receiving the full brain surgery that delivers the drug, the other where a sham surgery is performed and no drug is delivered. 

uniQure has previously shared data from their Phase 1/2 clinical trial suggesting that lowering of the huntingtin protein with AMT-130 seems to track with improved clinical measures

In this new potential design, the trial would also be double-blind, which means that neither the clinicians or participants would know who was in which group, although HDBuzz assumes the surgeons would know as the procedures would be quite different. 

A double-blind, placebo controlled study is generally considered the gold standard for determining whether a treatment truly works. However, in this specific scenario, it has faced criticism because of the ethical implications of asking people with HD to undergo an invasive procedure that may be a sham surgery, followed by a long period of monitoring. During this time (likely several years), participants would be unable to receive other potentially disease-modifying drugs currently advancing through clinical trials.

What happens next?

Although the FDA did not agree with uniQure’s proposed submission pathway based on existing Phase 1/2 data, discussions are apparently still ongoing. The company stated that it plans to request a Type B meeting with the FDA in the second quarter of 2026. The purpose of this meeting would be to further discuss Phase 3 development plans and possible clinical trial designs.

In its statement, uniQure emphasised their belief that the “totality and durability” of its data support continued dialogue with the agency and referenced the FDA’s commitment to regulatory flexibility in the case of serious diseases with high unmet need, where HD clearly fits.

Beyond the U.S., uniQure is still working to advance AMT-130 in Europe. The data collected from the ongoing trials at the European sites will still be informative for how effective the drug is in treating HD. If it’s able to advance through the regulatory pathway in Europe and demonstrate effectiveness, that will benefit the HD community across the globe, as uniQure could then use that data for future applications in the U.S.

What does this mean for the HD community?

For families affected by HD and all the stakeholders in this community, this news may feel very disappointing. It suggests that additional, larger, and more laborious trials will likely be required before AMT-130 could be considered for approval in the United States, delaying access for families to potential treatments while the clock keeps ticking.

At the same time, the FDA’s recommendation provides a clearer picture of what evidence they believe is necessary to move forward. While a randomised, sham-controlled surgical study presents practical and ethical challenges, it could also deliver the definitive answers needed about whether AMT-130 meaningfully slows disease progression. 

A double-blind, placebo controlled study is generally considered the gold standard for determining whether a treatment truly works

The uniQure update in September showing comparisons to an external control group suggested AMT-130 may slow disease progression, but was based on data from a very small number of people. With no direct placebo control group comparison, it’s possible that the results are less conclusive than regulatory agencies want to proceed with for a possible approval. Unfortunately, the data we have up to 12 months comparing to the sham control is less clear, and doesn’t show a definitive improvement for folks in the AMT-130 group in the small number of people tested.  

This does not mean the door is closed for other regulators either. While one of the most important drug regulation agencies, the FDA is just one in a global landscape of many organisations who each serve different constituencies around the world to approve new drugs. uniQure previously hinted that they are in conversations with other regulators, like those in Europe, so we will keep our eyes peeled for updates from these discussions. 

Gratitude for the HD community who brought us to this point

At moments like this, the HDBuzz team thinks back to our “save points” in the long and bumpy journey for drug development for HD, a concept from our Editor Emeritus, Ed Wild. 

Progress is only possible because of the selfless actions of the participants in these trials, the families who support participants, everyone who shows up to advocate for this community

In their September update, uniQure shared data that for the first time suggested that huntingtin lowering might offer benefits for people with HD. We knew at the time that there were many caveats and cautions, mainly that this was a tiny dataset and the external control arm was not favourably considered by everyone in the HD space. Nonetheless, uniQure’s data suggested that this approach was safe and could potentially move the needle for families living with HD. 

That data remains unchanged despite this turbulent ~5 months of back-and-forth with the FDA. We can always go back to this data as a jumping off point for how we can move forward as a community. We are not going backwards. 

This progress is only possible because of the selfless actions of the participants in these trials, the families who support participants, everyone who shows up to advocate for this community, and the tireless work from the people in this space to find drugs to treat HD. We are grateful to you all and thankful for everything you have done. 

Now, many in our community will take time to pause and regroup before we move forward again, as a global community to keep pushing to find drugs to help people with HD. 

As always, HDBuzz will continue to follow developments closely and provide updates as more information becomes available.

Summary: 

• On March 2, 2026, uniQure announced that the U.S. FDA communicated in their Type A meeting that the current Phase 1/2 data are not sufficient to support approval of AMT-130 for HD. 
• AMT-130 is an investigational gene therapy designed to lower huntingtin levels in the brain using an AAV-delivered microRNA, administered directly into the striatum via surgery. 
• The FDA disagreed with uniQure’s use of an external control group and recommended a new randomised, double-blind trial, potentially including a sham-surgery control arm. 
• While disappointing, discussions with regulators are ongoing, and clearer guidance from the FDA may help define the path forward for future trials and the HD community.