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.
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