Narcolepsy is a chronic sleep disorder that causes both excessive daytime sleepiness (EDS) and sudden episodes of muscle weakness known as cataplexy. This medical condition significantly impairs daily functioning and can lead to cognitive difficulties. Multiple treatments currently exist to manage narcolepsy, though most patients suffer from ongoing symptoms of the condition. AXS-12 is a new pharmaceutical developed by Axsome Therapeutics for treating narcolepsy through its effectiveness in reducing the frequency of cataplexy attacks among patients.
AXS-12 Â works by increasing brain levels of norepinephrine while simultaneously influencing dopamine to affect sleep-wake cycles. The Phase 3 SYMPHONY trial included testing AXS-12 to determine its effectiveness for treating the severe symptoms of narcolepsy type 1 (NT1) patients. The trial tests produced positive outcomes through rapid symptom relief in addition to a considerable decrease in cataplexy attacks alongside enhanced general symptom recovery.
The study included 15 to 75-year-old patients with NT1 who were randomly assigned to receive either AXS-12 or a placebo for five weeks. The participants were approved to keep taking their existing stable doses of modafinil and armodafinil, as well as other narcolepsy medications, during the study. The main research objective focused on understanding motor attack frequency modifications, but researchers also measured Exhaustive Daytime Sleepiness manifestations, cognitive capabilities, and health status of patients.
AXS-12 proved effective in decreasing the number of cataplexy attacks among patients. Patients receiving AXS-12 medication decreased their cataplexy attacks by 83% throughout Week 5, but placebo patients experienced only a 66% reduction. A statistically relevant improvement was proven through this improvement (p = 0.018). Notably, during Week 1, the patient group treated with AXS-12 achieved a 56% reduction in cataplexy attacks, whereas the placebo participants experienced a reduction of 31%.
One of the most notable findings was that AXS-12 helped a larger proportion of patients achieve “remission” of cataplexy, resulting in a complete (100%) reduction in attacks. Approximately 33% of patients treated with AXS-12 experienced complete remission of cataplexy attacks during Week 5, compared to only 9.5% of patients taking a placebo. A larger percentage of patients on AXS-12 reached remission by Week 2, in contrast to the placebo group, with 24% for AXS-12 and 4.5% for the placebo.
Patients taking AXS-12 experienced less severe EDS symptoms, which are the common debilitating symptoms of narcolepsy. Patients receiving AXS-12 showed an average Clinician Global Impression-Severity (CGI-S) scale decline of 1.8 points, while placebo patients received only a 0.9-point decline (p = 0.027) at Week 5. Clinical research showed a rapid reduction of EDS starting from the first week of treatment.
The study demonstrated that AXS-12 medication simultaneously improved cataplexy symptoms and symptoms related to EDS. At Week 5, the symptom improvement percentage for AXS-12 patients reached 57% for both cataplexy and EDS, while placebo patients recorded only 33% combined improvement.
Studies with AXS-12 showed that patients achieved better memory and concentration abilities through measurements from the Functional Outcomes of Sleep Questionnaire (FOSQ-10).
At Week 5, patients receiving AXS-12 had a marked improvement in cognitive function (p = 0.004). Improvement was particularly remarkable in those with a decrease in cataplexy attacks, with 41% of AXS-12 patients having both cognitive improvement and decreased cataplexy compared to just 17% of placebo patients.
The use of AXS-12 treatment resulted in better health status combined with improved functionality alongside enhanced life quality for patients. Studies documented a reduction in narcolepsy severity in AXS-12-treated patients compared to placebo participants, with a significance of p = 0.007 starting from Week 1 (p < 0.001). Patients who received this medication experienced meaningful enhancement of life quality based on FOSQ-10 total scores that showed significant improvements compared to placebo at Week 5 (p = 0.005). Depression and anxiety regularly complement the medical condition of narcolepsy in individuals.
The research data indicated that 45% of enrolled subjects presented with anxiety and depression symptoms during the study. The treatment group receiving AXS-12 indicated better improvements in both anxiety and depression compared to the placebo group, where only 32% of patients showed positive results.
The results of the SYMPHONY Phase 3 clinical trial indicate that AXS-12 shows strong potential to become a novel treatment solution for patients with narcolepsy. This medication proves effective in treating cataplexy attacks, simultaneously controlling symptoms of daytime fatigue and cognitive impairment and improving patient functioning. AXS-12 shows promise to become a significant medical solution for narcolepsy patients because it addresses unmet treatment needs, which provides meaningful benefits to both patients and their healthcare providers.
Dr. Michael Thorpy, a specialist in sleep disorders, was not only impressed by AXS-12 but commended its ability to bridge an important gap in therapies for narcolepsy patients who remain stuck with residual symptoms even after existing treatments. Axsome Therapeutics’ CEO, Dr. Herriot Tabuteau, also commended the success of the trial and outlined the company’s future direction after finishing ongoing safety trials to take AXS-12 to the market.
For individuals living with narcolepsy, the development of AXS-12 represents a potential breakthrough in improving quality of life and treating this challenging disorder.
References: Axsome Therapeutics. Axsome Therapeutics announces AXS-12 achieves primary endpoint in the SYMPHONY Phase 3 trial in narcolepsy. GlobeNewswire. Published March 25, 2024. https://www.globenewswire.com/news-release/2024/03/25/2851469/33090/en/Axsome-Therapeutics-Announces-AXS-12-Achieves-Primary-Endpoint-in-the-SYMPHONY-Phase-3-Trial-in-Narcolepsy.html
