Praxis Precision Medicines’ commitment to forging ahead with ulixacaltamide in essential tremor (ET) has paid off. After brushing off a recommendation to end a phase 3 study earlier this year based on an interim analysis, the company has come out with a win in that pivotal trial and another.
Ulixacaltamide is a selective inhibitor of T-type calcium channels that’s designed to block abnormal neuronal burst firing in the Cerebello-Thalamo-Cortical (CTC) circuit correlated with tremor activity. While a prior interim analysis suggested that patients taking the drug were no better off than those on placebo, Praxis’ topline results can now tell a different story.
The biotech used a decentralized, home-based study design for its two trials in the Essential3 phase 3 program, primarily weighing the drug’s effects through a scale that measures how tremor affects 11 specific daily activities (modified activities of daily living 11, or mADL11). This scale was adapted as the primary endpoint of the studies based on a previously failed phase 2.
In Study 1, which randomized 473 patients to receive either ulixacaltamide or placebo for 12 weeks, the trial drug elicited a statistically significant and clinically meaningful 4.3-point mean improvement in the mADL11 score at week 8, which was sustained from week 2 through the 12-week dosing period, Praxis said in an Oct. 16 release.
Study 2 enrolled 238 patients who received the trial drug for 8 weeks. Those who met the responder criteria were then randomized to receive a placebo or continue on ulixacaltamide for another 4 weeks. In that study, 55% of patients in the ulixacaltamide follow-up group maintained the response they had achieved by week 8, compared to 33% in the placebo group.
Rate of disease improvement, a key secondary endpoint in Study 2, also met the bar for statistical significance, Praxis said.
With the positive results in hand, the company has submitted a meeting request with the FDA to discuss a New Drug Application (NDA), which it plans to file by early 2026 upon agreement with the agency.
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Praxis’ stock skyrocketed more than 220% on Thursday morning, up some $130 from Wednesday’s closing price of $57.35. The development marks a major turnaround after the previously grim outlook from the interim analysis spooked investors and sent the company’s share price nosediving back in February.
“I am thrilled with the results of the Essential3 Program,” CEO Marcio Souza said. “In just 15 months of recruitment, we had over 200,000 people interested in participating in this study, which is a powerful reflection of the large unmet need for a therapy like ulixacaltamide. We look forward to the opportunity to have a pre-NDA meeting with the FDA soon to discuss the potential NDA.”
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Essential tremor is the most common movement disorder, affecting some seven million people in the U.S., according to Praxis. The only approved pharmaceutical treatment for the disease is the beta-blocker propranolol, which offers limited efficacy and can’t be used by many patients due to contraindications.
