Praxis Precision Medicines (Nasdaq: PRAX) reported that the Phase II/III POWER1 study of vormatrigine in adults with focal onset seizures did not meet its primary endpoint, though secondary data and a low discontinuation rate have left the company weighing whether a redesigned trial could salvage the program.
POWER1 is a double-blind, randomized, multicenter Phase II/III trial that enrolled adults with focal onset seizures who were concurrently taking between one and three anti-seizure medications. Patients received either vormatrigine — titrated from 20 mg once daily for six weeks to 30 mg once daily for a further six weeks — or placebo over a 12-week treatment period. The primary endpoint was percent change in monthly seizure frequency from baseline, and that measure was not met. The 50% responder rate, a secondary endpoint, was achieved, and seizure reduction during the second half of the study at the 30 mg dose was described as more pronounced than in the earlier titration phase, though no specific numerical values were disclosed. Adverse event-related discontinuations were below 10%, and approximately 90% of patients from the vormatrigine arm transitioned into an ongoing open-label extension. The combination of a missed primary endpoint with a met secondary measure and a dose-response signal at 30 mg creates an ambiguous dataset — consistent with a drug that may have been underpowered or inadequately dosed in the first half of the study, but not one that clearly demonstrates efficacy on its own terms.
Vormatrigine is a small molecule designed to selectively target the hyperexcitable, disease-state conformation of voltage-gated sodium channels, a mechanism Praxis has positioned as functionally distinct from conventional sodium channel blockers such as SK Life Science's Xcopri (cenobamate), which acts through both sodium channel inhibition and GABA-A modulation, or UCB's Vimpat (lacosamide), which enhances slow inactivation. The theoretical differentiation rests on state-dependent selectivity — the idea that vormatrigine preferentially engages channels in the pathological high-frequency firing state rather than at rest — though cross-trial comparisons are limited by differences in patient populations, concomitant medication rules, and endpoint definitions. Praxis has paused enrollment in the companion POWER2 study to reassess the program and consider protocol modifications; the timeline for any redesigned trial or next data readout has not been disclosed. The company said it remains focused on the planned launches of relutrigine and ulixacaltamide, two other late-stage candidates in its CNS portfolio.
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