uniQure Reports Positive Interim Data Showing Slowed Progression in AMT-130 Huntington’s Trials

uniQure N.V., a leading gene therapy company, has released updated interim results from its ongoing Phase I/II clinical trials of AMT-130, designed to treat Huntington's disease. The data includes follow-up information up to 24 months for 29 patients participating in the U.S. and European trials.

Dr. Walid Abi-Saab, the Chief Medical Officer of uniQure, expressed satisfaction with the statistically significant, dose-dependent reduction in disease progression and the lowering of neurofilament light protein (NfL) in cerebrospinal fluid (CSF) observed at 24 months. He emphasized that this is potentially the first investigational therapy for Huntington’s disease showing long-term clinical benefits and reduction in a neurodegeneration marker. Dr. Abi-Saab also highlighted the unique advantage of AMT-130's one-time administration in gathering extended patient outcome data from these studies.

Dr. Victor Sung from the University of Alabama at Birmingham praised the results, noting that the preservation of motor and cognitive functions over two years and the reduced NfL levels below baseline diverge from the expected natural progression of Huntington's disease. According to Dr. Sung, these findings offer substantial promise for the Huntington’s disease community, which is in dire need of therapeutic breakthroughs.

The trials involve two multi-center Phase I/II studies, with 26 patients in the U.S. and 13 in Europe/UK. Patients received either a low or high dose of AMT-130, while control patients underwent imitation surgery. As of the data cut-off on March 31, 2024, 21 patients had 24 months of follow-up data available for analysis.

A significant statistical analysis was conducted for the first time, comparing the clinical outcomes of 21 treated patients to an expanded, propensity-weighted external control group of 154 individuals. This control group was developed in collaboration with the Cure Huntington’s Disease Initiative (CHDI) using data from previous natural history studies. The external control included patients meeting the Phase I/II trial eligibility criteria, with their data statistically weighted to match the treated patients' baseline characteristics.

Patients receiving a high dose of AMT-130 exhibited a statistically significant dose-dependent slowing in disease progression as measured by the composite Unified Huntington’s Disease Rating Scale (cUHDRS). At 24 months, the high-dose group showed an 80% reduction in disease progression compared to the external control group, while the low-dose group exhibited a 30% reduction. Motor and cognitive functions remained nearly stable throughout the follow-up period for high-dose patients.

Furthermore, a significant reduction in CSF NfL levels was noted in patients treated with AMT-130, with mean levels below baseline for both doses at 24 months. This reduction stands in contrast to an independent study that found a 26% increase in CSF NfL levels in patients with early manifest Huntington’s disease over the same period.

AMT-130 was generally well-tolerated, with no new serious adverse events related to the treatment reported.

uniQure plans several next steps to advance the development of AMT-130. In the second half of 2024, the company expects to meet with the U.S. Food and Drug Administration (FDA) to present the updated data and discuss potential expedited clinical development pathways. They also anticipate completing the enrollment of a third U.S. cohort exploring AMT-130 in combination with immunosuppression. By mid-2025, uniQure aims to present another interim analysis including a 36-month comparison of treated patients to the external control group.

The company is conducting two multi-center, dose-escalating Phase I/II clinical trials to evaluate the safety, tolerability, and exploratory efficacy of AMT-130. The U.S. study involves 26 patients with early manifest Huntington’s disease, while the European study includes 13 patients. An additional cohort is being enrolled to explore both doses of AMT-130 in combination with immunosuppression.

Huntington’s disease is a rare, inherited neurodegenerative disorder characterized by motor symptoms, behavioral abnormalities, and cognitive decline, leading to progressive physical and mental deterioration. There are currently no approved therapies to delay the disease onset or slow its progression, emphasizing the urgent need for innovative treatment options like AMT-130.