uniQure announces update on Phase I/II trials of AMT-130 gene therapy

uniQure N.V. announced updated interim data including up to 30 months of follow-up from 39 patients enrolled in the ongoing U.S. and European Phase I/II clinical trials of AMT-130 for the treatment of Huntington’s disease. Updated Interim Data: Exploratory Efficacy Data: For patients receiving the high dose, neurological function as measured by cUHDRS and each of its individual components was preserved or improved at 18 months compared to pre-treatment baseline measurements. For patients receiving the low dose, neurological function as measured by Total Motor Score and Total Functional Capacity was preserved at 30 months compared to pre-treatment baseline measurements. When compared to the expected rate of decline from the natural history cohort, AMT-130 showed favorable trends in cUHDRS, TFC and TMS. composite Unified Huntington’s Disease Rating Scale: AMT-130 showed a favorable difference in cUHDRS of 0.39 points at 30 months and 1.24 points at 18 months for the low- and high-dose, respectively. Total Functional Capacity: AMT-130 showed a favorable difference in TFC of 0.95 points at 30 months in the low-dose and 0.49 points at 18 months in the high-dose. Total Motor Score: AMT-130 showed a favorable difference in TMS of 2.80 points at 30 months in the low-dose and 1.70 points in the high-dose at 18 months. Biomarkers and Volumetric Imaging Data: Neurofilament Light Chain: Mean CSF NfL for the low-dose cohort remained below baseline through month 30 and was 6.6% below baseline. Mean CSF NfL for the high-dose cohort also further declined and is near baseline at month 18. These data suggest a reduction in neurodegeneration when compared to an expected increase from baseline in CSF NfL based on natural history data. Mutant Huntingtin Protein: Given AMT-130 is directly administered deep within the brain, the pharmacodynamics of mHTT in the CSF are not believed to be materially representative of mHTT in the targeted brain regions. Total Brain Volume: Changes in the total brain volume of patients treated with AMT-130 were observed after the surgical procedure and trended below natural history. The volumetric changes do not appear to be clinically meaningful or associated with protracted increases in neurodegeneration as measured by NfL. Safety and Tolerability: AMT-130 was generally well-tolerated, with a manageable safety profile at both 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. There were four serious adverse events unrelated to AMT-130 in the low-dose cohort, six unrelated SAEs in the high-dose cohort, and one SAE in the control group. In addition, there were four AMT-130-related serious adverse events in the high-dose cohort, including central nervous system inflammation, and severe headache that, retrospectively, also was attributable to central nervous system inflammation.