PTCT · PTC Therapeutics, Inc.

PTC Therapeutics announced positive topline results from the 24-month interim analysis of the PIVOT-HD long-term extension study of votoplam in Huntington's disease. The study demonstrated dose-dependent slowing of disease progression on the cUHDRS scale in Stage 2 participants compared to a propensity-weighted natural history cohort from the ENROLL-HD registry. Specifically, the 10 mg dose showed a 52% slowing and the 5 mg dose showed 28% slowing. Importantly, the safety profile remained favorable with no new adverse event signals and no treatment-related increases in neurofilament light chain (NfL) protein; mean NfL levels remained below baseline at 24 months, contrasting with natural history where NfL increases over time. In Stage 3 participants, potential signals of slowing were observed. These results support the ongoing global Phase 3 INVEST-HD study initiated by Novartis, which will enroll approximately 770 early-stage HD patients randomized 3:2 to votoplam 10 mg or placebo, with a primary endpoint of change from baseline in cUHDRS up to 36 months. PTC and Novartis will review the data and discuss potential regulatory interactions. The positive interim data strengthen the case for votoplam as a disease-modifying therapy for Huntington's disease, a fatal genetic disorder with no approved treatments that slow progression.