Disease progression slowed by 80% at 24 months in phase 1/2 studies of HD gene therapy

Interim results of phase 1/2 clinical trials of an investigational gene therapy for Huntington’s disease showed that disease progression slowed by 80% at 24 months, according to the manufacturer.

In ongoing studies conducted in the United States (n = 26) and Europe (n = 13) for AMT-130, a total of 29 patients received one of two doses of AMT-130 (n = 12 low dose; n = 17 high dose) and 10 control patients received imitation surgery, Boston-based gene therapy company uniQure N.V. said in a press release.

At 24 months, the mean change in Composite Unified Huntington’s Disease Rating Scale (cUHDRS) for the high-dose cohort was -0.2 compared with -1 for patients in the propensity score-weighted external control, representing an 80% slowing of disease progression.

According to additional data cited in the release, mean change in cUDHRS for the low-dose cohort was -0.7 compared with -1 for patients in the propensity score-weighted external control, representing a 30% slowing of disease progression, also at 24 months.

Patients treated with AMT-130 recorded a mean reduction in cerebrospinal fluid neurofilament light chain (CSF NfL) of 11% compared with baseline at 24 months, while mean CSF NfL levels for both high and low doses were below baseline at the same interval. Interim data also showed AMT-130 to be generally well-tolerated, with a manageable safety profile at both high and low doses. No new treatment-related serious adverse events were reported.

The FDA granted regenerative medicine advanced therapy designation (RMAT) for AMT-130 in June. UniQure said in the release it anticipates engaging in a Type B, multidisciplinary RMAT meeting with the FDA to present updated data and discuss potential expedited clinical development pathways and accelerated approval in the second half of 2024.

“We are very pleased with these new data demonstrating a statistically significant, dose-dependent slowing of the progression of Huntington’s disease and lowering of [neurofilament light chain] in the [cerebrospinal fluid] at 24 months,” Walid Abi-Saab, MD, chief medical officer of uniQure, said in the release. “We believe this is the first clinical trial of any investigational medicine for Huntington’s disease to show evidence of a potential long-term clinical benefit and reduction of a key marker of neurodegeneration.”