Shares of uniQure experienced a sharp sell-off—crashing by roughly 40% in one of its worst single-day drops in over 10 months—following the release of four-year clinical data for AMT-130, its experimental gene therapy for Huntington’s disease.
The market reaction was driven primarily by a noticeable weakening in key efficacy metrics at the 48-month mark compared to earlier data releases, raising questions about the therapy’s long-term durability.
Key Takeaways from the AMT-130 Update
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Weaker cUHDRS Results at 48 Months: At the four-year mark, AMT-130 showed a 44% slowing of disease progression on the composite Unified Huntington’s Disease Rating Scale (cUHDRS) among 12 high-dose patients. However, this result missed statistical significance (nominal p-value of 0.144) and dropped substantially from the 80% slowing reported at the 36-month mark.
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TFC Measures Provided a Bright Spot: On the Total Functional Capacity (TFC) measure—which evaluates a patient’s ability to handle everyday activities—the therapy showed a 61% slowing of functional decline at 48 months with a statistically significant p-value of 0.008 (compared to 67% at 36 months).
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Control Group Complications: uniQure compared its 48-month data against an updated external control group from the ENROLL-HD dataset, noting that missing data rose to 53%. The company suggested that patients who dropped out progressed faster than those who stayed, potentially understating disease progression in the control group and making the treatment effect look smaller. Alternate post-hoc analyses using older control datasets showed stronger numbers (54% on cUHDRS and 68% on TFC).
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Regulatory Status & FDA Pathway: uniQure had already submitted its U.S. application for AMT-130 prior to the four-year data release. The FDA previously indicated that the stronger 36-month data could serve as the primary basis for a Biologics License Application (BLA) under the accelerated-approval pathway.
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Financial Position: Reports indicate uniQure holds roughly $414.6 million in cash against $50.1 million in long-term debt, though quarterly net losses remain substantial as a development-stage biotech firm.
What Investors Are Watching Next
Market attention has shifted heavily toward how the FDA will weigh the robust 36-month findings against the softer four-year cUHDRS readings during regulatory review. While uniQure maintains that the overall data points to a sustained treatment effect, the unexpected deceleration in the four-year composite score has undeniably heightened uncertainty around the program.
