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.