uniQure Shares Fall 64% After 48-Month AMT-130 Huntington's Disease Trial Update

uniQure N.V. (NASDAQ:QURE) shares fell 64% on Tuesday after the gene therapy developer reported updated 48-month data for ifezuntirgene inilparvovec, or AMT-130, its experimental treatment for Huntington’s disease.

The high-dose group continued to show a slower rate of disease progression compared with an external control group, but the result on the composite Unified Huntington’s Disease Rating Scale (cUHDRS) did not reach statistical significance at 48 months.

Among 12 high-dose patients, AMT-130 was associated with a 44% slowing of disease progression on the cUHDRS compared with the external control group, with a p-value of 0.144.

uniQure Attributes Result to Changes in External Control Group

uniQure attributed the 48-month statistical result to what it described as “survivor bias” in the updated matched external control dataset derived from ENROLL-HD.

According to the company, 53% of patients in the control group had dropped out by month 48 as their disease progressed. uniQure said this resulted in the remaining external control population being healthier on average, reducing the measured difference between the treated and control groups.

A post-hoc analysis using an earlier external control dataset showed a 54% slowing in disease progression on the cUHDRS, with a p-value of 0.041.

The post-hoc result represents an analysis conducted after the original analytical framework and should be considered separately from the primary 48-month comparison.

36-Month Data Remains Basis of Regulatory Filing

The company said the US Food and Drug Administration previously agreed that 36-month data would serve as the primary clinical basis for uniQure’s Biologics License Application under the accelerated approval pathway.

uniQure has already submitted the BLA for AMT-130, according to the supplied information.

An updated 36-month analysis involving 15 high-dose patients showed an 80% slowing of disease progression on the cUHDRS compared with the external control, with a p-value of 0.005.

The analysis also showed a 67% slowing in decline on the Total Functional Capacity measure, with a p-value of 0.011.

The FDA’s previous agreement regarding the basis of the filing does not guarantee approval, and the supplied information does not indicate that the agency has made a final regulatory decision.

Total Functional Capacity Result Remains Statistically Significant at 48 Months

At 48 months, high-dose AMT-130 patients showed a 61% slowing in functional decline as measured by Total Functional Capacity, with a nominal p-value of 0.008.

TFC assesses aspects of daily functioning in Huntington’s disease, including employment, financial management and the ability to perform everyday activities.

The company also reported differences between its high- and low-dose groups at four years. High-dose patients performed 1.03 points better on the cUHDRS and 0.40 points better on TFC compared with low-dose patients.

While the dose-related differences provide additional information about the observed treatment response, they do not independently establish efficacy or determine the FDA’s assessment of the therapy.

uniQure Reports Serious Adverse Events in Five High-Dose Patients

uniQure described AMT-130’s overall safety profile as generally manageable.

Five high-dose participants, representing 17% of that group, experienced treatment-related serious adverse events involving localised brain inflammation. According to the supplied information, all of those events resolved.

The company also reported that one low-dose participant died by suicide approximately five years after treatment. The study investigator determined that the event was unrelated to AMT-130.

The investigator’s determination represents an assessment of causality within the study and does not by itself establish the absence of treatment-related risk.

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