AXSM - Axsome Therapeutics Announces AXS-12 Achieves Primary Endpoint in the SYMPHONY Phase 3 Trial in Narcolepsy | Benzinga
AXS-12 statistically significantly reduced cataplexy attacks compared to placebo (p=0.018, primary endpoint)
AXS-12 achieved statistically significant remission of cataplexy compared to placebo (p=0.008)
AXS-12 statistically significantly reduced excessive daytime sleepiness (EDS) severity compared to placebo (p=0.027, CGI-S for EDS)
AXS-12 statistically significantly improved concentration and memory compared to placebo (p=0.004, Cognitive Function items of FOSQ-10)
AXS-12 statistically significantly reduced overall severity of narcolepsy compared to placebo (p=0.007, CGI-S for narcolepsy)
AXS-12 statistically significantly improved overall function and quality of life compared to placebo (p=0.005, FOSQ-10 total score)
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NEW YORK, March 25, 2024 (GLOBE NEWSWIRE) -- Axsome Therapeutics, Inc. (NASDAQ:AXSM), a biopharmaceutical company developing and delivering novel therapies for the management of central nervous system (CNS) disorders, today announced that AXS-12 (reboxetine), a highly selective and potent norepinephrine reuptake inhibitor and cortical dopamine modulator, achieved the primary endpoint and significantly reduced the frequency of cataplexy attacks as compared to placebo in patients with narcolepsy in the SYMPHONY Phase 3 trial. AXS-12 also reduced excessive daytime sleepiness (EDS) severity, improved cognitive function, and reduced overall narcolepsy severity as compared to placebo. SYMPHONY was a Phase 3 multicenter, randomized, double-blind, placebo-controlled trial in which 90 patients with a diagnosis of narcolepsy with cataplexy were randomized to treatment with AXS-12 or placebo for 5 weeks.
"AXS-12 is a novel therapeutic approach to the treatment of narcolepsy as evidenced by the strong clinical results generated from the Phase 3 SYMPHONY trial, including a rapid and significant reduction in cataplexy events compared to placebo," commented Dr. Michael Thorpy, Director of the Sleep-Wake Disorders Center at the Montefiore Medical Center and Professor of Neurology at Albert Einstein College of Medicine. "Despite the existence of multiple approved narcolepsy treatments, significant unmet need still exists given the high rates of persistent symptoms reported by patients. Based on the concurrent improvements observed on cataplexy, severity of excessive daytime sleepiness, cognition and overall function, I believe AXS-12 represents a meaningful enhancement to the treatment armamentarium for narcolepsy patients and clinicians and will be a welcome treatment option in our fight against the devastating impact of narcolepsy on patients and their loved ones."
AXS-12 met the primary endpoint by demonstrating a substantial and statistically significant reduction from baseline in weekly cataplexy attacks compared to placebo at Week 5, with reductions of 83% for AXS-12 and 66% for placebo (p=0.018). AXS-12 rapidly reduced weekly cataplexy attacks, demonstrating at Week 1 a reduction of 56% compared to a reduction of 31% for placebo (p=0.007).
AXS-12 induced remission of cataplexy and increased cataplexy-free days compared to placebo. Remission of cataplexy, defined as a 100% reduction from baseline, was achieved at Week 5 by 33% of AXS-12 treated patients compared to 9.5% of placebo patients (p=0.008). Achievement of remission was rapid, being experienced at Week 2 by 24% of AXS-12 treated patients compared to 4.5% of placebo patients (p=0.008). AXS-12 increased the percentage of cataplexy-free days per week, defined as days with zero cataplexy attacks, to 84.5% at Week 5 compared to 22.6% for placebo (p=0.014).
AXS-12 significantly reduced excessive daytime sleepiness (EDS) severity, assessed by the Clinician Global Impression of Severity (CGI-S) scale for EDS, compared to placebo at Week 5 with mean reductions of 1.8 points for AXS-12 compared to 0.9 points for placebo (p=0.027). Rapid improvement on the CGI-S for EDS was seen as early as Week 1 compared to placebo (p=0.006). AXS-12 concurrently improved EDS and cataplexy as compared to placebo. Concurrent EDS and cataplexy response was achieved at Week 5 by 57% of patients treated with AXS-12 compared to 33% of placebo patients (p=0.029). Concurrent EDS and cataplexy response was defined as a ?30% reduction in inadvertent naps (EDS response), and a ?50% reduction in cataplexy attacks (cataplexy response).
A decrease in the number of inadvertent naps was experienced by 54% of AXS-12 patients at Week 5 compared to 28% of placebo patients (p=0.016), assessed by the Narcolepsy Symptom Assessment Questionnaire (NSAQ). Improvement on the Epworth Sleepiness Scale (ESS) was numerically greater for AXS-12 than for placebo, with mean reductions from baseline of 4.7 points for AXS-12 compared to 3.4 points for placebo. A ?3-point improvement from baseline on the ESS was achieved by 60% of AXS-12 patients who had a cataplexy response.
AXS-12 significantly improved concentration and memory as measured by the Cognitive Function Items of the Functional Outcomes of Sleep Questionnaire (FOSQ-10) at Week 5 (p=0.004). AXS-12 concurrently improved cognition and cataplexy as compared to placebo. Concurrent cognitive and cataplexy response was achieved at Week 5 by 41% of patients treated with AXS-12 compared to 17% of placebo patients (p=0.016). Response was defined by an increase in days patients rated their Ability to Concentrate as very good or good (cognitive response), and a ?50% reduction in cataplexy attacks (cataplexy response).
AXS-12 improved narcolepsy overall disease condition, and patient function and quality of life. Clinicians reported a rapid and significant reduction in overall narcolepsy severity (CGI-S for narcolepsy overall) for patients treated with AXS-12 compared to placebo ...