J002 Twelve-month interim data from PIVOT-HD: a Phase 2, randomized, placebo-controlled study to evaluate the safety and efficacy of PTC518 in participants with Huntington’s disease
Year: 2024
Type: conference-abstract
Abstract: Background Huntington’s disease (HD) is caused by expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats in the huntingtin (HTT) gene which leads to the ubiquitous expression of toxic mutant huntingtin protein (mHTT). PTC518 is a splicing modifier that promotes inclusion of a pseudoexon (psiExon) containing a premature stop codon, leading to HTT messenger RNA degradation and lowering HTT levels. PIVOT-HD is a Phase 2, randomized, placebo-controlled, dose-ranging study to evaluate PTC518 in participants with HD (NCT05358717/2021-003852-18). Results from a 12-week interim analysis of 33 patients showed that PTC518 lowered blood mHTT protein in a dose-dependent manner. PTC518 exposure ratios in the cerebrospinal fluid (CSF) were consistent with or higher than the plasma unbound drug levels. Finally, PTC518 treatment was well tolerated, with no treatment-related serious adverse events and no dose-limiting toxicities. There were no treatment-related spikes in CSF and plasma neurofilament light chain protein. Aims Here we will present safety, clinical, and biomarker results from the planned interim analysis of PIVOT-HD that includes 12-month data for some participants. Methods/Techniques Participants with HD were randomized to receive PTC518 5 or 10 mg or placebo once daily for 12 months at 24 centers across Europe, Asia, and North America. Primary endpoints were the number of participants with adverse events and the change from baseline in blood HTT. Results/Outcome Additional interim analysis results will be presented. Conclusions These interim results will continue to demonstrate that PTC518 is a potential therapeutic for HD.
Institution: PTC Therapeutics (United States)
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4402374108