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UniQure's Huntington's Gene Therapy Shows 44% Disease Slowing At Four Years, Missing Its Primary Endpoint

Four-year data on AMT-130 fell well short of the 80% slowing reported in the updated three-year analysis, complicating a biologics license application already before the FDA.

Matteo Parrino Jonathan Ponciano

Matteo Parrino, Jonathan Ponciano

— 4 min read
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UniQure's Huntington's Gene Therapy Shows 44% Disease Slowing At Four Years, Missing Its Primary Endpoint

UniQure's Huntington's disease gene therapy, AMT-130, showed 44% slowing of disease progression at four years on its primary measure — a result that did not reach statistical significance and landed well below the 80% slowing the company had reported in its updated three-year analysis. The company disclosed the data in an 8-K filed Tuesday, raising the stakes for a biologics license application it had already submitted to the FDA before the four-year readout arrived.

What The Four-Year Data Show

The primary endpoint — the composite Unified Huntington's Disease Rating Scale, a combined measure of motor, cognitive, and functional decline — showed 44% slowing of disease progression in 12 high-dose patients compared to an external control group. The result carried a p-value of 0.144, meaning it did not reach statistical significance.

That figure represents a meaningful step down from the 80% slowing uniQure reported in its updated 36-month analysis, which covered all 15 high-dose patients and carried a nominal p-value of 0.005. The 36-month data also showed 67% slowing on Total Functional Capacity, a secondary measure, with a nominal p-value of 0.011.

A secondary measure at 48 months told a more favorable story. Total Functional Capacity — which serves as the primary endpoint in uniQure's planned confirmatory trial — showed 61% slowing with a nominal p-value of 0.008, and the company said the absolute treatment benefit seen at earlier timepoints held.

A post-hoc sensitivity analysis using the prior external control dataset put the four-year slowing figure at 53.5% on the composite scale, compared to 44% in the primary analysis using the updated control — a gap the company attributed to differences in the control populations.

Why The Primary Result Weakened — And What The Company Says About It

UniQure pointed to a specific methodological problem with the 48-month comparison: substantial data missingness in the external control group. More than half of the external control data used in the primary four-year comparison were absent, the company said, and its own analysis found that patients who dropped out of the control group had been declining faster than those who remained.

That pattern, the company argued in its clinical presentation filed Tuesday, likely understated the true treatment effect — because the control patients who stayed in the dataset were, on average, healthier than those who left, making AMT-130 look less effective by comparison than it may actually be.

The 48-month analysis used an updated external control drawn from the Enroll-HD natural history database — a dataset released in September 2025 that expanded the matched control pool to roughly 26,000 participants, compared to roughly 20,000 in the earlier version used for the 36-month analysis. The switch in control datasets, combined with the missingness problem, is central to understanding why the four-year primary result diverged from the three-year figure.

The Regulatory Path And What Came Before

The biologics license application uniQure submitted to the FDA earlier in September 2026 rests on the 36-month results from 12 high-dose patients — not the four-year data disclosed Tuesday. The company said the FDA communicated at a June 2026 meeting that those 36-month data would be acceptable under the accelerated approval pathway, and the application was filed before the four-year readout.

The road to that submission was not straightforward. The FDA initially rejected uniQure's plan to file for accelerated approval based on mid-stage trial data, then reversed that position, according to Fierce Biotech. The 36-month analysis that now anchors the application showed statistically significant 75% slowing on the composite scale (p=0.003) and statistically significant 60% slowing on Total Functional Capacity (p=0.033), results the company described as the regulatory anchor for both its U.S. biologics license application and its European marketing authorization application.

The four-year data were disclosed under Regulation FD — meaning they are now in the public domain and available to the FDA as it reviews the application, even though they were not part of the submission itself.

The Stock Move

QURE shares dropped sharply on Tuesday when the four-year data were first disclosed. By Friday, the stock had partially recovered, trading down less than 1% to $23.21 in Friday trading, according to market data.

What To Watch

The FDA's review of the biologics license application will determine whether the 36-month results from 12 high-dose patients are sufficient for accelerated approval. The agency has not yet set a target decision date based on the available material.

The four-year data — specifically the non-significant primary endpoint and the more favorable secondary measure — are now part of the public record the FDA will weigh alongside the submitted application. Whether the agency views the missingness-driven explanation for the weaker primary result as sufficient, or asks for additional data before acting, is the central question for holders of the stock.

The FDA has not set a target decision date for the biologics license application; the 36-month data from 12 high-dose patients, not Tuesday's four-year readout, remain the primary basis for the submission.

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