8-K: Axsome Therapeutics' AXS-12 Achieves Primary Endpoint in Phase 3 Narcolepsy Trial

Axsome Therapeutics announced that AXS-12 (reboxetine) significantly reduced cataplexy attacks compared to placebo in a Phase 3 trial for narcolepsy.

Summary

• Axsome Therapeutics' AXS-12 met its primary endpoint in the SYMPHONY Phase 3 trial, demonstrating a statistically significant reduction in weekly cataplexy attacks compared to placebo.
• The trial involved 90 patients with narcolepsy with cataplexy, who were randomized to receive either AXS-12 or a placebo for 5 weeks.
• AXS-12 showed an 83% reduction in cataplexy attacks at week 5, compared to a 66% reduction in the placebo group (p=0.018).
• A significant reduction in cataplexy attacks was observed as early as week 1, with a 56% reduction for AXS-12 compared to 31% for placebo (p=0.007).
• 33% of patients on AXS-12 achieved remission of cataplexy (100% reduction from baseline) at week 5, compared to 9.5% on placebo (p=0.008).
• AXS-12 also significantly reduced excessive daytime sleepiness (EDS) severity, with a mean reduction of 1.8 points on the CGI-S scale compared to 0.9 points for placebo (p=0.027).
• The drug improved concentration and memory, as measured by the Cognitive Function Items of the FOSQ-10 (p=0.004).
• AXS-12 also improved overall narcolepsy severity and patient function and quality of life, as measured by the CGI-S for narcolepsy (p=0.007) and the FOSQ-10 total score (p=0.005), respectively.
• The most common adverse events in the AXS-12 arm were dry mouth, nausea, and constipation, all of which were mild to moderate.
• The trial showed a low rate of discontinuation due to adverse events, with one patient in each arm discontinuing the trial.

Sentiment

Score: 9

Explanation: The document presents very positive results from a Phase 3 trial, with statistically significant improvements across multiple endpoints and a favorable safety profile. This suggests a high likelihood of regulatory approval and market success, leading to a very positive sentiment.

Positives

• AXS-12 demonstrated a substantial and statistically significant reduction in cataplexy attacks compared to placebo.
• The drug showed rapid improvement in cataplexy symptoms, with significant reductions observed as early as week 1.
• A significant percentage of patients achieved remission of cataplexy while on AXS-12.
• AXS-12 significantly reduced excessive daytime sleepiness (EDS) severity.
• The treatment improved cognitive function, specifically concentration and memory.
• AXS-12 improved overall narcolepsy severity and patient quality of life.
• The drug was well-tolerated with a low rate of discontinuation due to adverse events.
• AXS-12 has been granted Orphan Drug Designation, potentially providing market exclusivity and fee waivers.

Negatives

• The most commonly reported adverse events in the AXS-12 arm were dry mouth, nausea, and constipation, although these were generally mild to moderate.
• There was a small number of patients who discontinued the trial due to adverse events, one in each of the AXS-12 and placebo arms.

Risks

• The company's future success depends on the continued commercial success of their existing products and the success of their clinical trials.
• There are risks associated with obtaining and maintaining regulatory approvals for their product candidates.
• The company faces risks related to intellectual property protection and the successful implementation of their research and development programs.
• Market acceptance of the company's products and product candidates is not guaranteed.
• The company's anticipated capital requirements may be impacted by unforeseen circumstances or disruptions to normal business operations.

Future Outlook

The company plans to complete the ongoing open-label safety extension trial of AXS-12 and work towards bringing the treatment to individuals living with narcolepsy. They also plan to present the detailed results of the SYMPHONY trial at upcoming scientific meetings.

Management Comments

• Dr. Michael Thorpy stated that AXS-12 represents a meaningful enhancement to the treatment options for narcolepsy patients and clinicians.
• Dr. Herriot Tabuteau, CEO of Axsome Therapeutics, said that the SYMPHONY trial results confirm the promise and potential of AXS-12 for the treatment of narcolepsy.

Industry Context

The announcement is significant as it addresses the unmet need in narcolepsy treatment, where many patients continue to experience symptoms despite existing therapies. The positive results of the AXS-12 trial suggest a potential new treatment option with a novel mechanism of action.

Comparison to Industry Standards

• Current treatments for narcolepsy include wake-promoting agents, oxybates, stimulants, and antidepressants, but many patients still experience persistent symptoms.
• The SYMPHONY trial results show that AXS-12 has the potential to offer a more effective treatment option, particularly in reducing cataplexy, which is a significant burden for patients.
• The rapid reduction in cataplexy attacks and the achievement of remission in a notable percentage of patients are promising results compared to existing treatments.
• The concurrent improvements observed in cataplexy, excessive daytime sleepiness, cognition, and overall function suggest that AXS-12 may provide a more comprehensive approach to managing narcolepsy symptoms compared to some current therapies.

Stakeholder Impact

• Shareholders are likely to react positively to the strong clinical trial results.
• Patients with narcolepsy may benefit from a new treatment option that addresses multiple symptoms.
• Physicians will have a new therapeutic option for managing narcolepsy.
• Employees of Axsome Therapeutics may experience increased job security and opportunities for growth.

Next Steps

• The company will complete the ongoing open-label safety extension trial of AXS-12.
• Axsome plans to present the detailed results of the SYMPHONY trial at upcoming scientific meetings.
• The company will work to bring AXS-12 to individuals living with narcolepsy.

Key Dates

Keywords

AXS-12, narcolepsy, cataplexy, reboxetine, clinical trial, Phase 3, excessive daytime sleepiness, cognitive function, norepinephrine, dopamine