uniQure Shares Fall 64% as AMT-130's 48-Month Huntington's Data Miss Statistical Significance on Key Composite Measure

uniQure N.V. shares fell 64% after the gene therapy developer reported updated 48-month data for AMT-130 (ifezuntirgene inilparvovec), its experimental treatment for Huntington's disease, showing that the composite Unified Huntington's Disease Rating Scale (cUHDRS) measure did not reach statistical significance against an external control group, according to investorshub.advfn.com and Yahoo Finance.

What the 48-month update showed

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, according to investorshub.advfn.com. That result falls short of conventional statistical significance thresholds. Functional decline, measured separately by Total Functional Capacity (TFC), remained statistically significant, with high-dose patients showing a 61% slowing and a nominal p-value of 0.008, per the same reporting.

Using investorshub.advfn.com's reported figures, the 48-month cUHDRS result (44%) came in 17 percentage points below the TFC result (61%), a 27.9% relative difference (44 minus 61, divided by 61, times 100). This is our calculation based on the two reported figures and illustrates how the primary composite measure diverged from the secondary functional measure at the same 48-month readout.

uniQure's explanation: survivor bias

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 investorshub.advfn.com. The company said 53% of patients in the control group had dropped out by month 48 as their disease progressed, which it said left the remaining external control population healthier on average and reduced the measured difference between the treated and control groups.

A post-hoc analysis using the earlier external control dataset showed a 54% slowing of disease progression on the cUHDRS, with a p-value of 0.041, per the same reporting. Because that analysis was conducted after the original analytical framework, it should be considered separately from the primary 48-month comparison. Dose-related differences at four years showed high-dose patients 1.03 points better on the cUHDRS and 0.40 points better on TFC than low-dose patients, differences that, as the reporting notes, do not independently establish efficacy.

Safety and regulatory backdrop

On safety, five high-dose participants, or 17% of that group, experienced treatment-related serious adverse events involving localised brain inflammation, all of which resolved, according to investorshub.advfn.com. The same reporting said one low-dose participant died by suicide roughly five years after treatment, in an event the study investigator determined was unrelated to AMT-130.

uniQure has said the US Food and Drug Administration previously agreed that 36-month data would serve as the primary clinical basis for its Biologics License Application under the accelerated approval pathway, and reporting from investorshub.advfn.com and Yahoo Finance indicates the BLA has already been submitted. That reported agreement does not guarantee approval, and no final agency decision has been indicated. The pathway has shifted before: on November 3, 2025 the company said the FDA "currently no longer agrees" that data from the Phase I/II studies compared with an external control may be adequate as primary evidence for a BLA, according to HDBuzz, and on March 2, 2026 uniQure said the agency "strongly recommended uniQure conduct a prospective, randomized, double-blind, sham surgery-controlled study," a disclosure that sent shares down more than 40%, according to Fierce Biotech. HDBuzz also noted that AMT-130's Breakthrough Therapy and Regenerative Medicine Advanced Therapy designations were granted on the basis of the external control comparator, which "no longer appears to be sufficient for the agency."

Bottom line

The 48-month update left AMT-130's headline composite measure short of conventional statistical significance while the functional measure remained significant, a split uniQure ties to attrition in its external control set. Interpretation: with the comparator dataset itself now central to the debate, the weight regulators place on externally controlled evidence looks like the key variable for the program, a reading tied to the reported FDA statements above rather than to any confirmed agency decision. Before the setbacks, peak sales forecasts ranged widely, with William Blair's Sami Corwin projecting $4 billion by 2032, Goldman Sachs' Salveen Richter projecting $2.5 billion at a 90% probability of success, and Jefferies citing an analyst consensus of $1.7 billion, according to GEN. Those are third-party projections, not outcomes.