T-type calcium channel

A committee of outside clinical trial observers has recommended that Praxis Precision Medicines stop testing its experimental treatment for essential tremor after an interim analysis of one study concluded it is unlikely to succeed. Instead, Praxis is continuing that test and a second one, adding that a decision about an FDA submission will be made after a final analysis of both studies. The two separate and simultaneous studies are part of the Phase 3 trial design for the Praxis drug, ulixacaltamide. Both placebo-controlled studies are evaluating the once-daily pill over the course of 12 weeks. The main efficacy goal is assessing patients according to a composite scale that measures the ability to perform tasks of daily living. Essential tremor leads to involuntary shaking and trembling in arms and hands, though it can also affect a patient’s head and voice. An estimated 7 million patients in the U.S. have the neurological disorder, whose exact cause is unknown. The first line of essential tremor therapies for beta blockers. While such drugs were developed for high blood pressure, they are thought to also block nerve impulses to the muscles. Anti-seizure drugs offer an alternative treatment option. Healthcare Using Data to Help Healthcare Practices Succeed A new report from Relatient, A Data-Driven Guide to Patient Access Succes, highlights how focusing on data accuracy and relevance can enhance the performance of healthcare practices. By Relatient Ulixacaltamide is a small molecule inhibitor of T-type calcium channels. It’s designed to block abnormal neuronal burst firing in the cerebello-thalamo-cortical (CTC) circuit, which is correlated with tremor activity. Boston-based Praxis said Friday that based on the results of a planned interim analysis, the trial’s independent data monitoring committee recommended that Study 1 be stopped for futility, “due to the results being unlikely to meet the primary efficacy endpoint under the parameters set by the statistical model.” The targeted total enrollment of the two studies is 600 participants. Praxis said that given the advanced state of trial enrollment, it has decided to complete both studies. Preliminary results are expected in the third quarter of this year. Praxis added that the committee said some underlying assumptions of the statistical model might have influenced the futility finding and it encouraged the company to explore alternative analysis methods. In the Praxis announcement, CEO Marcio Souza said the company will explore different analysis methods for the final dataset that will be the basis for deciding whether to proceed with a regulatory submission. But investors took a dim view of the Praxis drug’s prospects. The biotech’s stock price tumbled Friday, closing at $38.60, down 40.6% from the Thursday’s closing price. Ulixacaltamide came from Cerebrum, Praxis’s proprietary technology for discovering small molecule drugs with the potential to treat central nervous system disorders. Formerly known as PRAX-944, ulixacaltamide is the most advanced drug candidate in the Praxis pipeline. Other drug candidates are in earlier stages of clinical development for various forms of epilepsy. Health IT Reducing Clinical and Staff Burnout with AI Automation As technology advances, AI-powered tools will increasingly reduce the administrative burdens on healthcare providers. By Dr. Michael Blackman, Chief Medical Officer at Greenway Health In its report of fourth quarter and full year 2024 financial results posted on Friday, Praxis stated it finished 2024 with $469.5 million in capital, a strong cash position that follows stock offerings completed last year. The company expects its cash will support operations into 2028. Image: Getty Images, Iaremenko

Praxis reported that its lead small molecule program failed a Phase 3 study on Friday morning, sending its stock price $PRAX down roughly 40%. The company was studying whether an experimental drug called ulixacaltamide could treat patients with essential tremor, a nervous system disorder that causes involuntary shaking. Typically, patients are treated with beta blockers or antipsychotic medications like Xanax, but ulixacaltamide is designed to inhibit T-type calcium channels. In a press release, Praxis said the trial’s independent data monitoring committee recommended the study stop early due to a high likelihood of futility. The primary endpoint was unlikely to be reached, the company said. But Praxis said it intends to complete the study, as well as another Phase 3 looking at the randomized withdrawal of ulixacaltamide, because the committee also “indicated that some underlying assumptions of the statistical model might have influenced this outcome.” Topline results for both trials are expected in the third quarter, after which Praxis will make a decision about whether to file for approval with the FDA. It wasn’t immediately clear what such underlying assumptions were or how they might have influenced the data. Praxis didn’t immediately return a request for comment. In a note to investors last month, TD Cowen analyst Ritu Baral said Praxis had intended to complete the trial regardless of the data committee’s findings. A futility finding likely would indicate “minimal to no separation” between ulixacaltamide and placebo, she added. Despite Friday’s fail, Praxis’ small molecule platform will continue to produce data readouts this year. The company is expecting open-label data for the epilepsy program vormatrigine in the first half of 2025, as well as Phase 2/3 data in the second half of the year.

Praxis Precision Medicines saw its shares plummet 40% on Friday after announcing that an independent data monitoring committee (IDMC) recommended stopping Study 1 of its Essential3 programme for ulixacaltamide (PRAX-944). The candidate, which targets T-type calcium channels to block abnormal neuronal burst firing in essential tremor, is unlikely to meet its primary efficacy endpoint, according to an interim analysis of the trial.However, Praxis says it still plans to bring both Study 1 and Study 2 of the programme to completion, with top-line results expected in the third quarter. It cited "advanced state of enrollment" and IDMC suggestions that "underlying assumptions of the statistical model might have influenced this outcome" as reasons for continuing the studies.Final dataset in Q3"We are disappointed with and surprised by the outcome of the interim analysis for Study 1," remarked CEO Marcio Souza. "Following the advice of the committee, we will explore different analysis methods for the final dataset, which is expected in the third quarter of 2025."Ulixacaltamide is the company's most advanced programme, and Praxis had anticipated a regulatory filing this year. The drug showed "meaningful improvement" in TETRAS Activities of Daily Living (ADL) measures among patients receiving propranolol, according to results from the Phase II Essential1 trial published in the journal Neurology last year.While Praxis reported on Friday that it had a solid financial position with nearly $470 million in cash, cash equivalents and marketable securities as of the end of last year, it also revealed a high cash burn rate, driven by an uptick in R&D expenses. These jumped to $56.3 million in the fourth quarter of 2024, compared to $18.4 million the same time a year earlier.Gap in near-term catalystsThe company's pipeline includes vormatrigine (PRAX-628), currently in trials for focal onset seizures and generalised epilepsy. The Phase II RADIANT study and Phase II/III POWER1 registrational study are expected to produce top-line results in mid-2025 and the second half of 2025, respectively. While showing promise in preclinical studies with "superior selectivity for disease-state NaV channel hyperexcitability," vormatrigine is still years away from potential commercialisation.Relutrigine (PRAX-562), an oral inhibitor of persistent sodium current for developmental and epileptic encephalopathies (DEEs), received its third Rare Pediatric Disease Designation from the FDA in December, this time for Dravet syndrome. The compound is currently in the mid-stage EMBOLD study for SCN2A and SCN8A DEEs, with headline results anticipated in the first half of 2026 and a regulatory filing later that year. Praxis plans to start the EMERALD study for DEEs by mid-2025.Finally, elsunersen (PRAX-222), an antisense oligonucleotide designed to decrease SCN2A gene expression, is being developed for early-seizure-onset SCN2A-DEE, and advancing with a finalised registrational trial design. The Phase III EMBRAVE3 study is expected to begin enrolling patients by mid-year.On a more positive note, Praxis said UCB exercised its option to in-license global rights for an KCNT1 small-molecule development candidate. This brings Praxis an option exercise fee and potential milestone payments totalling approximately $100 million, plus tiered royalties on net sales.