Axsome Therapeutics, Inc. has announced the topline results of the Paradigm Phase 3 proof-of-concept trial of Solriamfetol in major depressive disorder (MDD) with and without excessive daytime sleepiness (EDS). The study did not demonstrate a statistically significant change on the Montgomery-Åsberg Depression Rating Scale (MADRS) total score compared to placebo in the overall patient population, which was the study’s primary endpoint. However, in the prespecified subgroup of patients with severe EDS, treatment with Solriamfetol resulted in greater improvements in depressive symptoms compared to placebo.
The Paradigm study was a 6-week, randomized, double-blind, placebo-controlled, multicenter trial in the U.S., in which MDD patients with severe EDS and without severe EDS were randomized to treatment with Solriamfetol 300 mg or placebo. In MDD patients with severe EDS, Solriamfetol treatment resulted in clinically meaningful and numerically greater improvements compared to placebo on multiple efficacy measures including MADRS total score, MADRS anhedonia subscale, MADRS remission, clinical global impression of severity (CGI-S), clinical global impression of improvement (CGI-I), and patient global impression of improvement (PGI-I) at week 6.
It is reported that approximately 50% of MDD patients experience EDS, highlighting a high unmet need in this patient population. With EDS, patients have difficulty maintaining wakefulness and an increased propensity to fall asleep throughout the day, resulting in impairment of activities of daily living and increased safety risks. Currently, no therapies are approved to treat MDD with EDS.
Axsome Therapeutics plans to initiate a phase 3 trial in MDD patients with EDS in 2025 based on the results in the EDS subgroup. The company's Chief Executive Officer, Dr. Herriot Tabuteau, expressed satisfaction with the results and stated that the promising results with Solriamfetol in MDD patients with severe EDS align with its known pharmacology and support its further evaluation in this potentially new indication.
Solriamfetol was reported to be safe and well tolerated in the trial, with a side effect profile consistent with its established safety profile.
These results are important as MDD is a serious, common, biologically based disorder, and there is a high unmet need for effective treatments. According to the World Health Organization, depression is the leading cause of disability worldwide, and approximately 21 million adults in the U.S. are affected by MDD each year, with approximately two-thirds of patients experiencing inadequate response with first-line treatment.
Solriamfetol is a dopamine and norepinephrine reuptake inhibitor (DNRI), TAAR1 agonist, and 5-HT1A agonist being developed for the treatment of attention deficit hyperactivity disorder (ADHD), MDD, binge eating disorder (BED), and excessive sleepiness associated with shift work disorder (SWD).
Axsome Therapeutics is a biopharmaceutical company leading in the treatment of central nervous system conditions, with FDA-approved treatments for various disorders and multiple late-stage development programs addressing a broad range of serious neurological and psychiatric conditions.
The full results of the trial will be presented at future scientific conferences. The market has reacted to these announcements by moving the company's shares -5.5% to a price of $110.2. Check out the company's full 8-K submission here.
