uniQure Stock Plunges 41% as Huntington’s Gene Therapy Misses Key 48-Month Endpoint

Key points

• uniQure’s stock fell 41% to $23.15 at market open following the release of 48-month data for AMT-130.
• The primary endpoint, cUHDRS, showed a 44% slowing of disease progression but failed to reach statistical significance (p=0.144).
• The secondary endpoint, Total Functional Capacity (TFC), showed a 61% slowing of progression, consistent with the 60% result seen at 36 months.
• uniQure filed for accelerated FDA approval based on 36-month data, which showed an 80% slowing on cUHDRS when including three additional patients.
• The FDA had previously rejected the accelerated approval plan in March but reversed its stance, allowing the submission earlier this month.

Background

This development follows a turbulent regulatory path for AMT-130, where the FDA initially opposed the accelerated approval strategy before reversing its position. The broader context includes the lack of approved disease-modifying treatments for Huntington’s disease, making any slowing of progression clinically significant. Recent coverage of gene therapies, such as Genglycos for metabolic disorders, highlights the growing focus on long-term functional benefits in rare disease treatments.

How outlets are covering it

Fierce Biotech and GlobeNewswire emphasize the methodological issues with the external control group, noting that 53% of control data was missing and that patients who left the control group were declining faster, which likely understated the treatment benefit. Guggenheim Securities analysts echoed this, pointing to a single outlier in the control group that skewed results. In contrast, the market reaction was severe, with Yahoo Finance noting the stock was on track to shed half its market cap. However, uniQure CEO Matt Kapusta and Guggenheim analysts remained optimistic, focusing on the consistent performance of the TFC endpoint, which they view as the most direct measure of patient independence and daily function. Victor Sung, a neurology professor, highlighted the stability of functional capacity through month 48 as clinically meaningful despite the primary endpoint miss.

Why it matters

The outcome determines whether AMT-130 can achieve accelerated FDA approval, potentially offering the first disease-modifying treatment for Huntington’s disease. The divergence between the primary and secondary endpoints highlights the challenges in using natural history controls for rare diseases and may influence how the FDA evaluates future gene therapy submissions. For patients, the sustained functional benefits suggest a tangible improvement in quality of life, even if statistical significance on one metric was not met.

What to watch

The FDA will review the submitted BLA, which was based on 36-month data. uniQure will likely present these results at a future scientific meeting. The company must determine if the FDA will rerun the analysis with the new 48-month data cut or rely on the 36-month anchor. Investors will watch for any regulatory updates or further analyst revisions following the conference call.