Essential tremor drug succeeds in two key studies, persistence pays off
Seven months ago, an independent clinical trial observer reviewed interim data on Praxis Precision Medicines' essential tremor drug and recommended stopping the Phase 3 study. The practice continues. On Thursday, the biotech company reported successful results as it prepares to discuss an application with the FDA seeking regulatory approval for a drug that is expected to become a blockbuster drug many times over.
Essential tremor causes involuntary shaking and shaking of the arms and hands. For some patients, the disease affects the head and ability to speak. An estimated 7 million people in the United States suffer from essential tremor, a disease whose cause is unknown, Boston-based Praxis reports. There are currently no drugs specifically approved for essential tremor, although older blood pressure-lowering drugs and anti-seizure products are used to control the condition. Praxis CEO Marcio Souza said on a conference call Thursday morning that lack of efficacy and serious side effects have led many patients to stop taking the drugs.
“There are currently no specific drugs approved for essential tremor, and we are going to change that,” he said.
Ulixacaltamide is an oral small molecule designed to selectively inhibit T-type calcium channels in the brain, an approach designed to stop the abnormal bursts of neuronal firing associated with tremor. This in-house discovered drug comes from Praxis' platform technology for discovering small molecules with the potential to address central nervous system diseases.
Praxis is evaluating ulixacaltamide, a once-daily tablet, in two Phase 3 studies. The first study randomly assigned 473 participants to receive study drug or placebo for 12 weeks. Most of these patients are in their 60s and have had essential tremor for about 30 years. For many trial participants, symptoms worsened over the past three years despite taking available medications. The primary study objective was to evaluate patients on a composite scale measuring the ability to perform tasks of daily living. Preliminary results reported Thursday showed an improvement of 4.3 points on this scale compared with a 1.7-point change in the placebo group. Secondary objectives include measuring rates of disease improvement.
While preliminary results achieved statistical significance across the primary and secondary trial objectives, they were in stark contrast to an interim analysis planned earlier this year. In February, an independent data monitoring committee looked at the data to date and concluded that the study was unlikely to succeed based on the parameters set by the study's statistical model. While the committee encouraged Praxis to explore alternative analytical methods, it also recommended that this futile study be discontinued. No data details were revealed and the study remained blind.
When Praxis announced the committee recommendation in March, both Phase 3 studies were nearly fully enrolled, so Praxis decided to proceed. As for the committee's recommendations, Souza said the sample size at the time was small, and discontinuation of some patients could have led the committee to conclude that it was invalid.
Last month, Praxis updated the trial's statistical analysis plan, changing the primary target metric from day 84 to day 56. This change was made in consultation with the FDA and without any unblinding or analysis of the trial data. Souza explained that the company decided the most prudent approach was to review the Phase 2 study, which established the primary targets and drug doses for the pivotal clinical trial. The study evaluated ulixacaltamide for 56 days. Unblinded Phase 3 results now show statistically significant measurements at this point. Souza added that even without the changes, the trial was a success. Data released Thursday includes Day 84 results, which continue to show statistically significant improvement.
“In a sense, it really doesn't matter,” Souza said. “The trial was positive regardless of the timing of the analysis [day] 56 or 84. “
Praxis also reported results from a second placebo-controlled study, which enrolled 238 participants who were randomly assigned to receive either placebo or ulisakaramide for eight weeks. Of the 80 people who responded to ulisakaramide, half were randomized to withdraw from the study drug and switch to a placebo for four weeks. Regarding the primary goal of measuring maintenance of response to the experimental treatment, Praxis said that 55% of participants in the study maintained a response, compared with 33% of participants in the placebo group.
Ulixacaltamide is safe and well tolerated, with no adverse effects reported. Major side effects include constipation, dizziness, euphoria, and brain fog. Praxis said it plans to share more data from these studies at upcoming medical meetings and peer-reviewed publications. If discussions with the FDA go well, Praxis expects to submit a new drug application in early 2026.
It's too early to talk about drug pricing, and Souza wouldn't provide specific sales forecasts for the drug. Even so, he said the lower end of Praxis' estimate for ulixacaltamide sales is in the mid- to high-single digits of billions of dollars for a disease that affects millions of Americans and for which there is currently no effective treatment.
Praxis shares plummeted after the data commission's ineffective recommendations were revealed in March. The company's shares soared on Thursday, closing at $162.71, up more than 183% from Wednesday's closing price. The company is taking advantage of the rising stock price to lay the groundwork for a proposed public offering.
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