uniQure Plunges 64% as AMT-130 48-Month Data Misses Endpoint

uniQure N.V. shares plummeted 64% after updated 48-month clinical data for its experimental Huntington's disease gene therapy, ifezuntirgene inilparvovec (AMT-130), missed statistical significance on a primary composite endpoint due to high control group attrition, according to an Investing.com report. The sharp sell-off occurred despite earlier 36-month findings remaining intact to support the company's submitted Biologics License Application.

The composite Unified Huntington's Disease Rating Scale (cUHDRS) at 48 months showed a 44% slowing of disease progression compared to an external control group for 12 high-dose patients, yielding a non-significant p-value of 0.144.

"uniQure attributed the statistical miss to 'survivor bias' within its updated ENROLL-HD matched external control dataset," according to the Investing.com report.

Analyzing the 48-Month Control Group Attrition

The clinical setback stems largely from how long-term data was benchmarked against natural history cohorts. uniQure noted that 53% of control patients dropped out of the ENROLL-HD matched external control dataset by month 48.

This high dropout rate left a disproportionately healthier control group, skewing the comparative analysis. However, a post-hoc analysis utilizing a prior external control dataset restored statistical significance, demonstrating a 54% slowing on the cUHDRS with a p-value of 0.041.

High-dose patients maintained a 61% slowing of functional decline at 48 months on the Total Functional Capacity (TFC) metric, securing a nominal p-value of 0.008.

Safety Profile and Regulatory Standing

Aside from efficacy metrics, the clinical trial data highlighted specific neurological safety considerations for the gene therapy. Five high-dose participants, representing 17% of that cohort, experienced treatment-related serious adverse events involving localized brain inflammation. The company confirmed that all of these events ultimately resolved.

The market reaction centers heavily on the long-term durability question, yet regulatory filings rely on an earlier window. The FDA previously agreed that 36-month data would serve as the primary clinical basis for uniQure's BLA under the accelerated approval pathway, which has already been submitted.

The updated 36-month analysis, encompassing 15 high-dose patients, demonstrated an 80% slowing of disease progression based on the cUHDRS (p=0.005) and a 67% slowing based on Total Functional Capacity (p=0.011), insulating the active regulatory application from the 48-month statistical miss.