Praxis Precision Medicines reported topline results from the Phase 2/3 POWER1 trial of vormatrigine in focal onset seizures, missing the primary endpoint but showing secondary efficacy signals and strong safety, prompting a pause in POWER2 enrollment.
Written By: Nikita Jha, BPharm
Reviewed By: Pharmacally Editorial Team
Praxis Precision Medicines reported topline results from the Phase 2/3 POWER1 study (NCT06999902) evaluating vormatrigine in adults with focal onset seizures (FOS). The trial failed to meet its primary endpoint of percent change in monthly seizure frequency, prompting the company to pause enrollment in the ongoing POWER2 study while it reassesses the program.
Trial Design and Results
POWER1 was a randomized, double-blind, placebo-controlled study that enrolled adults with focal onset seizures receiving one to three background anti-seizure medications. Participants received vormatrigine 20 mg once daily for six weeks followed by 30 mg once daily for another six weeks, or placebo for 12 weeks.
Although the study missed its primary endpoint, vormatrigine showed activity on key secondary measures. The trial met its prespecified 50% responder rate endpoint, demonstrating that a meaningful proportion of patients achieved at least a 50% reduction in seizure frequency.
Praxis also reported greater seizure reduction during the second half of treatment when patients received the 30 mg dose, suggesting a potential dose-response effect that may inform future development decisions.
Safety and Patient Retention
Vormatrigine was generally well tolerated, with fewer than 10% of patients discontinuing treatment because of adverse events.
Long-term retention remained high, with approximately 90% of patients from the vormatrigine arm transitioning into the ongoing open-label extension study and remaining on therapy.
Mechanism and Prior Data
Vormatrigine is a next-generation sodium channel modulator that selectively targets hyperexcitable neuronal sodium channels associated with seizure activity. Preclinical studies suggest it may provide greater selectivity for disease-associated sodium channel hyperexcitability than conventional sodium channel blockers.
The therapy previously demonstrated notable seizure reductions and favorable tolerability in the Phase 2 RADIANT study, supporting its continued evaluation in epilepsy.
Clinical Implications
President and Chief Executive Officer Marcio Souza acknowledged that POWER1 did not achieve its primary objective but highlighted the efficacy signal observed at the higher dose, low discontinuation rates, and favorable safety profile.
Praxis will conduct a detailed review of the complete dataset to determine the most appropriate path forward for vormatrigine and the POWER2 program. Meanwhile, the company continues preparations for the anticipated launches of relutrigine and ulixacaltamide, which remain key late-stage assets within its CNS portfolio.
Reference
Praxis Precision Medicines Provides Vormatrigine Program Update – Praxis Precision Medicines, Inc.
About the Writer
Nikita Jha, BPharm (LinkedIn) a pharmacy graduate specializing in medical writing, with a strong ability to interpret complex medical and regulatory information and translate it into clear, accurate, and evidence-based healthcare content. Known for her attention to detail and precision, she focuses on delivering high-quality scientific communication that supports drug safety and informed decision-making.