PTC Therapeutics reports ‘positive’ results from PIVOT-HD study

PTC Therapeutics (PTCT) reported positive topline results from the 24-month interim analysis of the PIVOT-HD long-term extension study, with favorable dose-dependent effects on disease progression for Stage 2 Huntington’s disease patients following 24 months of votoplam treatment compared to an external natural history cohort. “These results give us confidence in the potential for votoplam to deliver long-term meaningful effect on slowing Huntington’s disease progression,” said Matthew B. Klein, M.D., Chief Executive Officer, PTC Therapeutics. “In particular, the evidence of dose-dependent slowing of progression on the cUHDRS disease rating scale in the Stage 2 study participants supports the Novartis-initiated Phase 3 INVEST-HD study. We look forward to continuing to review the data and aligning on potential regulatory interactions based on the results with our partner Novartis.” The PIVOT-HD study was a 12-month placebo-controlled study of two dose levels of votoplam in participants with Stage 2 and Stage 3 HD. The study met the primary endpoint of blood Huntingtin protein lowering at 12 weeks, with persistent dose-dependent lowering at Month 12. PIVOT-HD participants then enrolled in the PIVOT-HD extension study in which those originally randomized to receive 5 mg or 10 mg of votoplam remained on those dose levels. Participants initially randomized to receive placebo were randomized to receive 5 mg or 10 mg. All participants and investigators remain blinded to initial PIVOT-HD treatment assignment. The objectives of the long-term extension study are to assess the safety and efficacy of long-term votoplam treatment. In the interim analysis following 24 months of votoplam treatment, there was evidence of dose-dependent benefit in slowing progression on the Composite Unified Huntington’s Disease Rating Scale relative to a propensity weighted natural history cohort in Stage 2 participants, with 52% and 28% slowing for 10 mg and 5 mg participants, respectively. Signals of favorable treatment effects relative to natural history were recorded across the cUHDRS subscales for the 10 mg cohort. In addition, there were no treatment-related neurofilament light chain protein (NfL) increases and mean NfL levels remained below baseline at 24 months for both high and low dose cohorts – in contrast to the reported natural history that NfL levels increase over time in individuals with HD. In Stage 3 participants, potential signals of slowing of progression were observed at 24 months. Importantly, the safety data at Month 24 for both dose levels and both stages were consistent with the previously established evidence of favorable safety.