uniQure falls as Huntington’s gene therapy shows mixed results
uniQure’s shares fell about 40% in early trading on September 29 after its Huntington’s gene therapy missed statistical significance on the main disease progression measure after four years. The Dutch biotech reported continued slowing of decline with AMT-130, but the update complicates the durability picture as the company seeks regulatory approval.
Why it matters: Huntington’s disease causes progressive movement, cognitive and behavioral problems, with no approved treatment that slows its progression. AMT-130 could offer a first disease-modifying option, but its evidence relies on a small patient group compared with an external database.
Zoom in: The latest Phase 1/2 analysis included 12 patients who received the high dose and reached four years of follow-up.
- On the composite Unified Huntington’s Disease Rating Scale, which assesses cognition, movement and daily functioning, progression was 44% slower than in matched external controls but the difference was not statistically significant.
- On Total Functional Capacity, which measures abilities such as working, managing household tasks and self-care, decline was 61% slower, which the company considers “a favorable treatment difference”, according to a press release.
- The expanded three-year analysis looked stronger: Among 15 high-dose patients, progression was 80% slower on the composite scale and 67% slower on functional capacity.
The catch: These percentages depend on how quickly the comparison group declines. uniQure used an updated ENROLL-HD natural history dataset, in which 53% of four-year follow-up data were missing.
- The company said patients who dropped out had been progressing faster than those who remained. That could make the external controls appear healthier and reduce the estimated treatment benefit.
- A post hoc analysis using the previous control dataset produced a 54% slowing on the composite scale and 68% on functional capacity. However, changing the comparator after the analysis does not resolve the uncertainty.
How it works: AMT-130 delivers genetic instructions for a microRNA designed to silence the huntingtin gene, reducing production of the protein implicated in the disease. It is administered once through MRI-guided surgery directly into the brain.
What’s next: As we reported in June, the FDA agreed that uniQure’s earlier three-year data could form the primary basis of an accelerated approval application. The company has since submitted that application, along with a separate filing in the U.K. It has also requested FDA priority review, which, if granted, would shorten the review to six months after an initial 60-day filing assessment.
- The FDA must still decide whether the evidence supports approval. Accelerated approval would require a confirmatory study to verify clinical benefit; uniQure says the latest data update was not included in its submitted U.S. application.
