UniQure’s Huntington’s Gene Therapy Data Weaken at 48 Months; Shares Plunge 41%

UniQure’s gene therapy for Huntington’s disease, AMT-130, failed to significantly slow disease progression at 48 months, sending the company’s shares sharply lower.

According to Fierce Biotech on the 29th (local time), UniQure released 48-month follow-up data for 12 participants in a phase 1/2 clinical trial. The rate of slowing disease progression, measured by the composite Unified Huntington’s Disease Rating Scale (cUHDRS), was 44%, down sharply from 75% at the 36-month mark a year earlier. The result did not reach statistical significance.

Following the news, UniQure shares fell 41% shortly after the market opened, reaching $23.15. Analysts and company executives, however, viewed the data positively. UniQure CEO Matt Kapusta said on an investor conference call that the data trend was “positive and meaningful” for patients. Guggenheim Securities analysts also expressed optimism about AMT-130 in an investor note.

The optimism stemmed from questions about the implications of missing the primary endpoint and the strength of the secondary endpoint. CEO Kapusta said more than half of the external control data used in the 48-month primary endpoint analysis were missing.

“Patients who dropped out of the control group deteriorated significantly faster than those who remained,” he said. “Over time, the comparison group came to reflect a healthier population than at baseline, and this bias worked against AMT-130, leading to an underestimate of the treatment effect.”

Guggenheim analysts said the external comparator “may have several methodological flaws.” In particular, they noted that a single outlier accounted for about one-third of the total cUHDRS worsening between 36 and 48 months. UniQure reported a 54% rate of slowing cUHDRS disease progression in a post hoc analysis using its previous external control group.

The impact of the weaker cUHDRS data was offset by stable performance on the secondary endpoint. Total Functional Capacity (TFC) showed a 61% rate of slowing disease progression at 48 months, reproducing the 60% rate at 36 months. TFC is the primary endpoint in UniQure’s confirmatory clinical trial.

“TFC is the measure that most directly captures what matters to patients and their families,” CEO Kapusta said. “It shows whether they can keep their jobs, manage their finances and carry out daily activities independently.”

UniQure applied to the U.S. Food and Drug Administration (FDA) for accelerated approval based on 36-month AMT-130 data compared with its previous external control group. UniQure Chief Medical Officer Waleed Abisaab said the company would respond if asked whether the FDA would rerun the analysis using the new data: “If the FDA requests it or conducts it itself, we will respond.”

AMT-130’s path through the FDA approval process has had its twists and turns. The FDA rejected UniQure’s plan in March to seek accelerated approval based on phase 1/2 data, but reversed its position several months later, and UniQure applied for accelerated approval earlier this month.