uniQure announces update on Phase I/II trial of AMT-130

uniQure announced promising interim data, including up to 24 months of follow-up, from 26 patients enrolled in the ongoing U.S. Phase I/II clinical trial of AMT-130 for the treatment of Huntington’s disease. Data Summary from the U.S. Phase I/II Trial of AMT-130 in Huntington’s Disease: A total of 26 patients with early-manifest Huntington’s disease have been enrolled in the multi-center, U.S. Phase I/II clinical trial of AMT-130. Safety and Tolerability: AMT-130 was generally well-tolerated, with a manageable safety profile in patients treated with the lower dose of 6×1012 vector genomes and the higher dose of 6×1013 vector genomes. The most common adverse events in the treatment groups were related to the surgical procedure. No treatment emergent adverse events led to discontinuation of patient follow-up. Exploratory Efficacy Data: Clinical and functional measurements for treated patients in each dose cohort were compared to baseline measurements, control patients and a natural history cohort. The cohort includes 31 patients that met the uniQure clinical trial inclusion-criteria of CAG length, age, Total Functional Capacity, Diagnostic Classification Level and minimum striatal volumes. Early clinical data demonstrate trends consistent with a potential clinical benefit of AMT-130 at both doses of AMT-130. Compared to baseline measurements, clinical function was generally preserved at 24 months for patients in the low-dose cohort and at 12 months for patients in the high-dose cohort. Compared to natural history, patients in both dose cohorts demonstrated benefits in each of Total Motor Score, Total Functional Capacity and the composite Unified Huntington’s Disease Rating Scale. Patients in the control group experienced a worsening of Total Motor Score at 12 months compared to baseline and natural history. TFC and cUHDRS was preserved in control patients at 12 months. Biomarkers: Neurofilament light chain: As expected and as previously reported, patients treated with AMT-130 experienced a transient increase in CSF NfL related to the procedure that peaked at approximately one month after administration. Mean CSF NfL for the low-dose cohort was 12.9% below baseline compared to a predicted 22.9% increase in the natural history, with four of the five low-dose patients having CSF NfL levels below baseline. In the control group, mean CSF NfL was relatively stable and was 6.83% below baseline at 12 months. Mutant Huntingtin protein: CSF mHTT for the low-dose cohort remained below baseline with a mean reduction of 8.1% at 24 months. Total Brain Volume: The mean total brain volume for the control, low-dose and high-dose cohorts declined 0.74%, 1.02% and 1.23%, respectively at 12 months and were not significantly different from each other or from the natural history. Next Steps: Based on the promising data from this interim analysis, uniQure will advance the clinical development of AMT-130 and anticipates the following next steps: Early in the third quarter of 2023, uniQure expects to complete patient enrollment in the high-dose cohort of the European clinical trial. In the second half of 2023, uniQure expects to initiate a third cohort in the ongoing U.S. clinical trial. In the fourth quarter of 2023, uniQure expects to present new clinical data from the Phase I/II studies of AMT-130.