Vormatrigine

iStock, Azurhino Praxis’ vormatrigine reduced seizures by 56.3%, an effect size that, according to analysts at Truist Securities, exceeds that of its closest competitors. Praxis Precision Medicines’ vormatrigine cut seizures by more than half in a Phase II trial of patients with focal onset seizures, giving the investigational sodium channel blocker momentum as a pivotal study approaches completion. Over eight weeks of treatment, patients on vormatrigine experienced a 56.3% median decrease in seizure frequency, according to a statement from Praxis on Monday. The study, dubbed RADIANT, also found that in roughly 22% of treated patients, seizures completely ceased over the last 28 days of treatment. Vormatrigine also appeared to act quickly, with more than 54% of RADIANT participants hitting a 50% reduction in the first week. Writing to investors on Monday, analysts at Truist Securities called Praxis’ readout “impressive,” noting that vormatrigine cleared “a high bar set by [SK Life Science’s] Xcopri and [Xenon Pharmaceuticals’] XEN-1101,” two of its closest competitors in the seizure space. According to its label , Xcopri reduces seizure frequency by 55.6%, whereas an October 2023 readout put XEN-1101’s efficacy at 52.8% . “Results [for vormatrigine] are all the more impressive given no need for titration and relatively clean safety profile,” the analysts added. “Given vormatrigine targets sodium channel, a first-line target, we expect broad utilization if approved.” Taken once daily orally, vormatrigine is an investigational small-molecule drug that binds sodium channels in the brain and blocks hyperexcitable states. Aside from RADIANT, Praxis is also studying vormatrigine in the registrational Phase II/III POWER1 and POWER2 studies in focal onset seizure. POWER1 is expected to be completed by the end of the year , while POWER2 is scheduled to start in the third quarter and finish enrollment in the back half of next year. Praxis appears to have enough cash to see vormatrigine through these milestones. In its second-quarter earnings report on Monday, the biotech said it still had $447 million in cash and investments, enough to keep it afloat into 2028. The biotech is operating in the red, however: Its losses widened to $71.1 million in Q2 versus $37.2 million during the same period last year. Aside from Praxis, SK and Xenon, Neurona Therapeutics is also working in the seizure space with its investigational cell therapy NRTX-1001. A readout in April 2025 demonstrated a 92% median reduction in disabling seizures over 7–12 months in patients with treatment-resistant epilepsy. Neurona will move NRTX-1001 into Phase III trials, with enrollment set to start in the latter half of this year.

Praxis said the drug candidate was generally well tolerated, but 23% of patients discontinued the study. \n Praxis Precision Medicines has reported a 56.3% median reduction in seizure frequency from baseline in a midphase trial, encouraging the biotech to push ahead with phase 2/3 plans despite almost a quarter of patients discontinuing the epilepsy trial.This morning\'s readout came from 37 focal onset seizure patients who received the sodium-channel modulator vormatrigine in Praxis’ Radiant study. The drug candidate was generally well tolerated, according to Praxis, but 23% of patients discontinued the study.Of the patients who stuck with the treatment, the Boston-based biotech said (PDF) that 60% experienced at least a 50% reduction in seizure frequency over eight weeks.The company saw improvements early, with 54% of patients hitting the 50% threshold in Week 1, and it tracked a deepening of the responses over time. In the last month of the dataset, 22% of the patients experienced a 100% reduction in seizure frequency, according to an August 4 release.Praxis saw the responses in patients who were receiving other anti-seizure medications. More than 80% of participants were taking a sodium channel blocker and 30% were on SK Life Science’s Xcopri. Steven Petrou, Ph.D., chief scientific officer at Praxis, hailed the consistent efficacy across subgroups of patients on different background therapies as a strength of the study.“The bar in Radiant was especially high. This was the first epilepsy study launched and reported in the U.S. following widespread adoption of [Xcopri],” Petrou said on a call with investors to discuss the data.“This level of consistency, in both efficacy and tolerability, across different treatment backgrounds speaks to vormatrigine’s versatility,” Petrou added. “It reinforces the idea that this is a therapy with broad applicability.”Explaining the discontinuation rate, Petrou said many of the dropouts were linked to a lack of background therapy dose adjustment, despite protocol guidance. Adverse events and discontinuations “were avoided entirely” in six instances where investigators proactively reduced background treatment, the Praxis executive pointed out.  The discontinuation rate may explain the lackluster reaction from investors to this morning\'s readout, with shares in the biotech down nearly 14% to $46.68 in Monday trading from a Friday closing price of $54.09.During the trial, vormatrigine\'s efficacy was not impacted by the dialing back of other medications, Praxis CEO Marcio Souza said on the investor call. Souza used the finding to advance Praxis’ argument that vormatrigine could become a standalone therapy.“I think what we established is that the background therapy is not doing anything but causing side effects, and vormatrigine is getting these patients better,” Souza said. “So a monotherapy study, or a switch to monotherapy, makes a lot of sense.”Praxis is planning to start a monotherapy trial in the first half of 2026. Before then, the company is set to kick off a follow-up to Radiant, enrolling a larger patient population to receive placebo or one of three doses of vormatrigine.