Praxis Precision Medicines Faces Setback in Phase 3 Essential Tremor Trial

Praxis Precision Medicines, a biotechnology company focused on developing treatments for central nervous system disorders, has encountered a significant obstacle in its phase 3 clinical trial for ulixacaltamide, a potential treatment for essential tremor. Despite receiving a recommendation to halt the study due to futility concerns, the company has made the unusual decision to continue both of its ongoing late-stage trials to completion.

Interim Analysis Reveals Disappointing Results

An independent data monitoring committee conducted an interim analysis of the first phase 3 trial, which involved randomizing participants to receive either ulixacaltamide or a placebo for 12 weeks. The primary endpoint of the study was based on a daily living scale, designed to measure the impact of the treatment on patients' ability to perform routine tasks affected by essential tremor.

The committee's analysis suggested that patients receiving ulixacaltamide were not showing significant improvement compared to those on placebo. As a result, they advised Praxis to stop the trial for futility, indicating that it was unlikely to meet its primary endpoint.

Praxis Defies Recommendation, Continues Trials

In a surprising move, Praxis has chosen to disregard the committee's recommendation and proceed with both of its late-stage trials. The company's decision is based on two main factors:

1. Advanced enrollment in both studies
2. Feedback from the committee suggesting that "some underlying assumptions of the statistical model might have influenced" the futility finding

Praxis CEO Marcio Souza had previously expressed high confidence in the trial's design, stating at the J.P. Morgan Healthcare Conference in January that there was "a priori, less than 3% probability of being futile." This sentiment was echoed by Chief Financial Officer Tim Kelly, who reiterated that futility was "very unlikely" in recent events.

Market Reaction and Future Outlook

The news of the potential trial failure has had a significant impact on Praxis's stock price, with shares dropping more than 40% in premarket trading to around $38. Despite this setback, the company ended 2024 with a substantial cash reserve of $469.5 million.

Praxis expects to have topline data from both phase 3 trials in the third quarter of this year. The company will then decide whether to file for approval based on the final results. The second ongoing trial has a different design, allowing Praxis to assess whether patients maintain their responses after being randomized to either ulixacaltamide or placebo.

As the pharmaceutical industry closely watches the outcome of these trials, Praxis Precision Medicines faces a critical juncture in its development of ulixacaltamide for essential tremor. The company's decision to continue the trials despite the interim setback underscores the complexities and risks inherent in late-stage clinical development.