Praxis Precision Medicines has been blindsided by a recommendation to stop a phase 3 essential tremor trial. Two months after CEO Marcio Souza said the chances of the trial being futile were “less than 3%,” the biotech has learnt the study looks unlikely to meet its primary endpoint at an interim analysis.
The phase 3 trial is one of two late-stage studies of ulixacaltamide in essential tremor. Participants in the first trial were randomized to receive the study drug or placebo for 12 weeks. Based on a failed phase 2 trial, the biotech picked a daily living scale as its primary endpoint. The scale captures how the disease is affecting a patient’s ability to perform tasks such as getting dressed.
An interim analysis suggests patients on ulixacaltamide are doing no better than their peers on placebo. The independent data monitoring committee that carried out the analysis advised Praxis to stop the trial for futility because it is unlikely to meet its primary endpoint.
Despite that, Praxis has chosen to continue both late-stage trials to completion. Praxis is pushing ahead because enrollment in both studies is advanced and in light of feedback from the committee, which told the biotech “some underlying assumptions of the statistical model might have influenced” the futility finding. The committee encouraged Praxis to explore alternative analysis methods.
Praxis expects to have topline data from the two trials in the third quarter and will decide whether to file for approval after analyzing its final results. The second trial has a different design that allows Praxis to assess if patients maintain their responses after being randomized to ulixacaltamide or placebo. Praxis previously ran a similar withdrawal trial. Patients in the earlier trial relapsed after stopping therapy.
Going into the interim analysis, Praxis was bullish about the prospects of the committee giving it the okay to continue the trial. At the J.P. Morgan Healthcare Conference in January, Praxis CEO Souza said the study had “a priori, less than 3% probability of being futile, the way it was designed.” Praxis chief financial officer Tim Kelly reiterated the message that futility was “very unlikely” at events this month.
Souza and Kelly’s confidence was underpinned by knowledge of the options available to the committee. The committee could recommend adding hundreds of participants to the trial in response to the interim analysis, suggesting Praxis had a path to success even if its assumptions about the statistical powering of the study were too aggressive.
The failure of the trial to clear the bar for a continuation recommendation spooked investors, who sent the biotech’s share price down more than 40% to around $38 in premarket trading. Praxis ended 2024 with $469.5 million.