Based upon observed efficacy and safety profile, Praxis intends to engage with the FDA in an end of Phase 2 meeting and initiate a ulixacaltamide Phase 3 study for the treatment of essential tremor in 2H23
Ulixacaltamide demonstrated improvement in modified Activities of Daily Living (mADL) primary efficacy endpoint relative to placebo that did not reach statistical significance (p=0.126), and achieved nominal statistical significance in TETRAS-ADL secondary endpoint (p=0.026)
Nominal statistically significant improvements observed in Clinical Global Impression-Severity (CGI-S) and in Patient Global Impression-Change (PGI-C)
Ulixacaltamide was well tolerated in the Essential1 study, with no new safety findings
Company to host conference call to discuss the results at 8:00 a.m. ET
BOSTON, March 03, 2023 (GLOBE NEWSWIRE) -- Praxis Precision Medicines, Inc. (NASDAQ: PRAX), a clinical-stage biopharmaceutical company translating genetic insights into the development of therapies for central nervous system (CNS) disorders characterized by neuronal excitation-inhibition imbalance, today announced topline results from the Essential1 study evaluating the efficacy, safety and tolerability of ulixacaltamide (PRAX-944) for the treatment of essential tremor (ET).
In Essential1, ulixacaltamide treated participants demonstrated improvement relative to placebo participants in the primary endpoint, change from baseline to Day 56 in the modified Activities of Daily Living (mADL1) score, that did not reach statistical significance. Nominal statistically significant improvement was observed in the TETRAS-ADL score secondary endpoint. Additional secondary endpoints were supportive of the ulixacaltamide efficacy profile, including nominal statistically significant improvements in the Clinical Global Impression-Severity (CGI-S) and Patient Global Impression-Change (PGI-C) scores. Praxis intends to engage with the FDA in an end of Phase 2 meeting and initiate a Phase 3 study for the treatment of essential tremor in the second half of 2023 based upon the observed efficacy and safety profile.
“The impact of essential tremor transcends the action tremor that is the hallmark of the disease. Essential tremor can be debilitating, causing significant disruption of everyday activities. There is significant unmet need for an effective and tolerable precision medicine that can improve patient functioning, and to date there exists no medicine specifically developed for tremor,” said William G. Ondo, M.D., Professor of Neurology at the Houston Methodist Hospital and Weill Cornell Medical College. “The results from Essential1 give hope to the essential tremor community that a targeted therapy is within reach, and we eagerly anticipate additional data from the ulixacaltamide program.”
“The results from Essential1 illustrate the clear potential of ulixacaltamide as an effective and well tolerated treatment for people with essential tremor,” said Marcio Souza, president and chief executive officer of Praxis. “The study showed meaningful improvement in patient’s daily functioning, while also providing insights to guide the program’s advancement to Phase 3, including a deeper understanding of endpoints and trial design. It’s clear to us based on these results and prior clinical experience, that ADLs are the preferred endpoint for a registrational study for essential tremor. We look forward to meeting with the FDA to discuss the data and our Phase 3 plans.”
Essential1 Efficacy Results
Essential1 is a randomized, double-blind, placebo-controlled, dose-range-finding Phase 2b trial evaluating the efficacy, safety and tolerability of once-daily daytime treatment of 60 or 100 mg of ulixacaltamide compared to placebo after 56 days. The primary endpoint for the study was the change from baseline to day 56 in the mADL score. A total of 132 patients with essential tremor were randomized and treated in the study.
The primary analysis population was the modified intention to treat (mITT2). In the mITT analysis (n=116), ulixacaltamide (n=78) showed numerical difference versus placebo (n=38) at day 56 in the mADL score (-3.01 points for ulixacaltamide treated participants, -1.44 for placebo participants [LS mean difference 1.58; 95% CI: -3.60, 0.45; p=0.126]) and nominal statistical significance versus placebo at day 56 in the TETRAS-ADL secondary endpoint (-3.60 points for ulixacaltamide treated participants, -1.07 for placebo participants [LS mean difference 2.53; 95% CI: -4.75, -0.31; p=0.026]). Consistent effect was observed across both the 60 mg and 100 mg dosing regimens. Observed changes across 10 of the 12 ADL scored items in the mITT favored ulixacaltamide treated participants relative to placebo and there were no items that favored placebo.
Patients and clinicians reported higher overall impression of improvement with ulixacaltamide relative to placebo. In the PGI-C, 47% of ulixacaltamide treated patients reported improvement, while 30% of placebo participants reported improvement (p