Praxis' vormatrigine misses main goal in POWER1 focal seizure trial
The Phase 2/3 study missed its primary seizure-frequency endpoint, but a secondary responder measure hit and the higher 30 mg dose showed more seizure reduction late in the trial.
Executive Summary
- Praxis Precision Medicines' Phase 2/3 trial of vormatrigine in focal onset seizures missed its primary endpoint, a result the company disclosed after the trial completed.
- A responder-rate secondary endpoint was met, and seizure reduction was more pronounced during the later, higher-dose period of treatment, giving the sponsor a narrower basis to keep developing the drug.
- Praxis is pausing enrollment in its next-stage confirmatory trial for the same drug to reassess the program, a direct operational consequence of the primary miss.
- The drug was generally well tolerated, with a low rate of adverse-event-related discontinuations, keeping the safety profile as the one clean result from the trial.
What was tested
POWER1 was a double-blind, randomized, quadruple-masked Phase 2/3 trial that enrolled 230 adults with focal onset seizures who were taking one to three other anti-seizure medications. Patients received either vormatrigine, 20 mg daily for six weeks followed by 30 mg daily for another six weeks, or placebo for 12 weeks. The primary endpoint was the percent change in monthly seizure frequency from baseline, measured against placebo. Praxis disclosed on June 1, 2026 that the trial did not meet this endpoint. NCT06999902+1Double-blind, Randomized Trial of PRAX-628 in Adults With Focal Seizures to Evaluate Efficacy and Safety (POWER1)NCT06999902Praxis Precision Medicines Provides Vormatrigine Program UpdateJun 1, 2026
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
What held up
A secondary endpoint, the proportion of patients achieving at least a 50% reduction in seizure frequency, was met. Praxis also reported that seizure reduction was more pronounced during the second half of the study, when patients were on the higher 30 mg dose, than during the initial 20 mg period. Adverse-event-related discontinuations were below 10%, and the company characterized the safety profile as favorable. Marcio Souza, president and chief executive officer of Praxis, said the company was "encouraged by the signal we saw on the higher dose arm, the low discontinuation rate and safety profile". PraxisPraxis Precision Medicines Provides Vormatrigine Program UpdateJun 1, 2026
The program response
Praxis is pausing enrollment in POWER2, a separate Phase 3 trial evaluating vormatrigine in the same indication, to reassess the program and consider modifications. Roughly 90% of patients who received vormatrigine in POWER1 transitioned into and remain in an open-label extension study, a retention figure the company disclosed alongside the primary miss. The company's own registered trial record shows enrollment held flat at its 230-patient target with no protocol amendments to the primary endpoint or eligibility criteria before the readout, so the miss was not preceded by design instability. Praxis+1Praxis Precision Medicines Provides Vormatrigine Program UpdateJun 1, 2026Double-blind, Randomized Trial of PRAX-628 in Adults With Focal Seizures to Evaluate Efficacy and Safety (POWER1)NCT06999902
Where it sits in the field
Focal seizures draws a field of small-molecule sodium-channel and other mechanism programs, including Rapport Therapeutics' RAP-219 and SK Life Science's cenobamate, both in Phase 3 testing, alongside earlier-stage entrants such as Jazz Pharmaceuticals' cannabidivarin program. None of the identified peer programs share a confirmed target with vormatrigine, so the primary competitive comparison rests on indication and modality rather than mechanism. Praxis has a second registrational trial of vormatrigine, NCT07505004, still recruiting in the same indication, which will need to weigh how it interprets the POWER1 dosing pattern.
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.