PTC Therapeutics Reports Positive 24-Month Data for Votoplam in Huntington's Disease Extension Study

PTC TherapeuticsSearch company announced positive topline results from the 24-month interim analysis of the PIVOT-HD long-term extension study, demonstrating dose-dependent benefits of votoplamSearch drug in slowing Huntington's diseaseSearch disease progression in Stage 2 patients compared to a matched natural history cohort.

The results showed 52% slowing of disease progression for patients receiving the 10mg dose and 28% slowing for those on the 5mg dose, as measured by the Composite Unified Huntington's DiseaseSearch disease Rating Scale (cUHDRS). These findings have supported NovartisSearch company's decision to initiate the global Phase 3 INVEST-HD study.

Dose-Dependent Efficacy Signals

In Stage 2 participants who received 24 months of votoplamSearch drug treatment, the study demonstrated evidence of dose-dependent benefit in slowing progression on the cUHDRS relative to a propensity weighted natural history cohort. The 10mg cohort showed signals of favorable treatment effects across the cUHDRS subscales.

"These results give us confidence in the potential for votoplamSearch drug to deliver long-term meaningful effect on slowing Huntington's diseaseSearch disease progression," said Matthew B. Klein, M.D., Chief Executive Officer of PTC TherapeuticsSearch company. "In particular, the evidence of dose-dependent slowing of progression on the cUHDRS disease rating scale in the Stage 2 study participants supports the NovartisSearch company-initiated Phase 3 INVEST-HD study."

Biomarker and Safety Profile

The study revealed no treatment-related neurofilament light chain protein (NfL) increases, with mean NfL levels remaining below baseline at 24 months for both high and low dose cohorts. This contrasts with reported natural history showing that NfL levels increase over time in individuals with Huntington's diseaseSearch disease.

In Stage 3 participants, potential signals of slowing of progression were observed at 24 months. The safety data at Month 24 for both dose levels and both stages remained consistent with the previously established evidence of favorable safety.

Phase 3 Study Launch

Based on these extension study results, NovartisSearch company announced the initiation of the global Phase 3 INVEST-HD study. This placebo-controlled study will enroll approximately 770 individuals with early-stage HD who will be randomized 3:2 to receive votoplamSearch drug 10mg or placebo. The primary endpoint will be the change from baseline up to month 36 in the cUHDRS.

Study Design and Mechanism

PIVOT-HD was originally designed as a 12-month placebo-controlled trial assessing pharmacodynamic effect and safety of votoplamSearch drug at 5mg and 10mg doses relative to placebo. The study initially included Stage 2 patients, with a Stage 3 cohort subsequently added to identify the optimal study population for future trials.

VotoplamSearch drug is a small molecule splicing modifier that promotes the inclusion of a novel pseudoexon containing a premature termination codon, triggering HuntingtinSearch term (HTTSearch term) mRNA degradation and subsequent reduction in HTT protein levels. The drug was discovered from PTC's validated splicing platform and was partnered with NovartisSearch company in December 2024.

Unmet Medical Need

Huntington's diseaseSearch disease is a fatal, hereditary genetic disorder of the central nervous system caused by a defective gene that produces abnormal HTTSearch term protein, leading to neuron damage and death. The disease typically presents in people in their 30s or 40s and results in abnormal movements, difficulties with speech, swallowing and walking, along with behavioral, cognitive and motor symptoms. Currently, there is no cure for HD and no approved drugs that delay onset or slow disease progression.