uniQure’s Huntington’s disease gene therapy AMT-130 lost momentum in updated long-term data, with the company reporting a 44% slowing of disease progression on the composite Unified Huntington’s Disease Rating Scale at month 48 in a phase 1/2 cohort of 12 patients. The result was not statistically significant, a weaker outcome than the 75% slowing uniQure had linked to the therapy at month 36 a year ago.
Investors responded immediately, pushing the biotech’s stock down 41% when trading began. The market reaction suggests that even after the Food and Drug Administration allowed an accelerated approval filing earlier this month, confidence in the durability and interpretability of the evidence remains fragile.
The Data
The main issue in the update was deterioration in the cUHDRS comparison over time rather than a collapse across all measures. uniQure said more than half of the external control data used in the month 48 primary endpoint analysis are missing. CEO Matt Kapusta said the patients who left the control were declining markedly faster than those who remained, meaning the comparator increasingly reflected a healthier population than at baseline.
Guggenheim Securities analysts took a similar view, saying the external comparator may have several methodological flaws. They also said a single outlier contributed approximately one third of the overall cUHDRS degradation between month 36 and month 48.
uniQure also reported a post hoc analysis using the prior external control, which showed a 54% slowing of cUHDRS disease progression. That does not erase the weaker headline result, but it matters because the current debate is as much about the quality of the comparator as about the biology of AMT-130 itself.
A secondary endpoint provided the clearest support for the program. Total functional capacity showed a 61% slowing of disease progression at month 48, essentially replicating the 60% result seen at month 36. Kapusta described TFC as the most direct measure of what patients and families care about because it captures whether someone can hold a job, manage finances, and perform daily tasks needed for independent living.
The Road Here
AMT-130’s regulatory path has already shifted more than once. In March, the Food and Drug Administration rejected uniQure’s plan to file for accelerated approval based on the phase 1/2 data. Months later, the agency reversed its opposition, leading uniQure to file for accelerated approval early this month.
That history makes the latest readout strategically important beyond the stock move. The filing is already in, but the updated dataset introduces a new question about which analysis the agency will rely on and how much weight it will place on disputed external-control methodology versus the steadier functional endpoint.
Chief medical officer Walid Abi-Saab said it is difficult to speculate on whether the Food and Drug Administration will rerun the analysis with the new data cut. That leaves uniQure in a familiar position for hard-to-study neurologic diseases: defending directional efficacy in a small dataset while regulators decide how much uncertainty they will tolerate.
