AMT-130 Huntington’s Disease Gene Therapy: Clinical Study Outcomes at Three Years
Victor Sung1, Grzegorz Witkowski2, Erin Furr-Stimming3, Ali Samii4, Christopher Ross5, Bradley Elder6, Ralf Reilmann7, Jeffrey Long8, Vicki Wheelock9, Claudia Testa10, Samuel Frank11, Kenechi Ejebe12, Wenfei Zhang12, Walid Abi-Saab13, David H Margolin12
1University of Alabama At Birmingham, 2Military Institute of Aviation Medicine, 3University of Texas Health Science Center-Houston, 4University of Washington Medical Center, 5Johns Hopkins University School of Medicine, 6The Ohio State University College of Medicine, 7George Huntington Institute, 8University of Iowa, 9University of California Davis Health in Sacramento California, 10University of North Carolina at Chapel Hill, 11Beth Israel Deaconess Medical Center/Harvard Medical School, 12uniQure Inc, 13uniQure GmbH
Objective:
To evaluate the effectiveness of AMT-130 on 3-year clinical progression in participants with Huntington’s disease (HD), relative to a natural history (NatHx) control cohort.
Background:
AMT-130 is an investigational huntingtin (HTT)-lowering gene therapy undergoing clinical evaluation in the U.S. (NCT04120493) and Europe (NCT05243017; EudraCT 2020-001461-36).
Design/Methods:
AMT-130 was administered as one-time bilateral intra-striatal infusions at low- or high-dose levels. Clinical outcomes were assessed in 29 participants treated with AMT-130 (17 at high-dose and 12 at low-dose). Twelve participants per group completed 36 months of follow-up. Outcomes for each dose group were compared with a propensity score matched cohort from the Enroll-HD NatHx study (high-dose: n=940; low-dose: n=626). The primary clinical effectiveness outcome was change from baseline to year 3 in the composite Unified Huntington’s Disease Rating Scale (cUHDRS), analyzed using a mixed model for repeated measures. The key secondary endpoint was change from baseline to year 3 in Total Functional Capacity (TFC). Adverse events (AEs) and laboratory results were regularly assessed in AMT-130 trial participants.
Results:
The study of AMT-130 high-dose met the primary endpoint of cUHDRS change from baseline at 36 months versus a NatHx cohort. High-dose AMT-130 mean change in cUHDRS over 36 months was -0.38 vs -1.52 for a matched natural history cohort (p=0.003), and mean change in TFC was -0.36 vs -0.88 for a matched natural history cohort over 36 months (p=0.033), with trends supportive of disease slowing across all other clinical subdomains of cUHDRS. Variable trends in functional, motor, and cognitive endpoints were observed in the AMT-130 low-dose cohort. AMT-130 was generally well tolerated and had a manageable safety profile across both dose levels.
Conclusions:
High-dose AMT-130 met its primary and a key secondary endpoint at 36 months compared with a well-matched NatHx cohort control, with positive trends seen on additional clinical and supportive measures.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.