Praxis’ Vormatrigine Shows Significant Ability to Reduce Seizure Incidence in Phase 2 RADIANT Study

Jacqueline French, MD

Recently announced findings from the phase 2 RADIANT study (NCT06908356) showed that treatment with Praxis’ vormatrigine, a functionally selective small molecule, led to significant attenuation of seizures among those with focal onset seizures. Additional data from the study is expected to be presented at the upcoming International Epilepsy Congress (IEC), taking place August 31, in Lisbon, Portugal.¹

The open-label trial featured patients with focal onset or primary generalized tonic-clonic seizures concurrently taking at least 1, but no more than 3 acceptable anti-seizure medications prior to entering. Over the 8-week treatment period, treatment with 30 mg/day of vormatrigine led to a 56.3% median reduction in seizure frequency, with 54% of patients achieving at least a 50% response in the first week.

The data, which included 37 patients who received the investigational agent, showed that vormatrigine was well tolerated, although 23% of the patients discontinued the study. Among those who continued on with treatment, approximately 22% of patients achieved a 100% reduction in seizure frequency in the last 28 days on treatment.

"While several sodium channel therapies are already used to treat focal onset seizures, there remains substantial room for improvement within this class. A next-generation sodium channel blocker has the potential to represent an important step forward in addressing that gap," Jacqueline French, MD, professor of neurology at NYU Langone’s Comprehensive Epilepsy Center, said in a statement.¹ "I'm encouraged by the initial results of the RADIANT study and hopeful that, in the future, we may be able to offer patients another effective treatment option."

A compelling next-gen sodium-channel modulator, vormatrigine is designed with precision targeting and patient-friendly dosing. The drug’s clinical program currently includes two phase 3 studies: POWER1 and POWER2, as well as another study, POWER3, slated for initiation in 2026. POWER1 is an ongoing registrational study targeting focal onset seizures, expected to complete later this year, while POWER2 is a multi-dose trial kicking off in the second half of this year with enrollment through mid-2026.

Marcio Souza, MD, PhD

"These findings build on our earlier clinical data showing a differentiated profile for vormatrigine as a fast-acting, no-titration, once-daily oral drug with no requirement to be taken with food, and a favorable DDI profile, all of which are unseen in ASMs currently in the market or in development,” Marcio Souza, MD, PhD, president and chief executive officer at Praxis, said in a statement.¹ "We are well on track to complete the pivotal, 12-week POWER1 study in Q4 and, based on the results from RADIANT, expect to initiate the POWER2 study shortly."

READ MORE: The Transition of Care from Pediatric to Adult Neurology: Leaving the Cocoon

In early 2024, Praxis announced positive topline data from a phase 2a proof-of-concept study of vormatrigine in 10 patients with epilepsy who have photo paroxysmal response (PPR). Each patient received 15 mg or 45 mg of vormatrigine, dubbed PRAX-628 at the time, or placebo, with EEG signatures recorded over a 24-hour period following treatment. All told, the 45 mg dose was more effective, as 100% of treated patients achieved a complete response to treatment.²

Complete response to treatment was defined as a reduction to 0 in the number of generalized PPR events. The 15 mg group, which had data available for 5 of the 6 treated patients, showed a complete response rate of 80% (4 of 5), with 1 patient showing partial response. Notably, 3 of the patients in the 15 mg cohort participated in the 45 mg cohort after a washout period of more than 100 days.

In a previous completed phase 1 study of 40 healthy volunteers, vormatrigine was generally well tolerated across all tested doses, with no serious adverse events, withdrawals, or clinically significant findings on ECG, vital signs, or neurological exams. Participants were randomized to PRAX-628 (n = 30) or placebo (n = 10), with single-ascending dose cohorts (5–45 mg) and multiple-ascending dose cohorts (20 mg and 30 mg) achieving drug exposures more than 15-fold higher than the mouse MES EC50. The most common treatment-related adverse events were fatigue, dizziness, somnolence, headache, disturbance in attention, and nausea.³

REFERENCES
1. Praxis Precision Medicines Announces Positive, Best-in-Disease Topline Results in Patients with Focal Onset Seizures from the RADIANT Study of Vormatrigine. News release August 4, 2025. Accessed August 12, 2025. https://www.globenewswire.com/news-release/2025/08/04/3126507/0/en/Praxis-Precision-Medicines-Announces-Positive-Best-in-Disease-Topline-Results-in-Patients-with-Focal-Onset-Seizures-from-the-RADIANT-Study-of-Vormatrigine.html
2. Praxis Precision Medicines reports positive results of PRAX-628 study evaluating photo paroxysmal response (PPR) achieving 100% response in treated patients. Praxis Precision Medicines. March 26, 2024. Accessed August 12, 2025. https://www.globenewswire.com/news-release/2024/03/26/2852195/0/en/Praxis-Precision-Medicines-Reports-Positive-Results-of-PRAX-628-Study-Evaluating-Photo-Paroxysmal-Response-PPR-Achieving-100-Response-in-Treated-Patients.html
3. Praxis Precision Medicines announces positive topline results from PRAX-628 phase 1 study enabling best-in-class profile. Praxis Precision Medicines. May 11, 2023. Accessed August 12, 2025. https://investors.praxismedicines.com/news-releases/news-release-details/praxis-precision-medicines-announces-positive-topline-results