8-K: Axsome Therapeutics Announces Positive Phase 3 Results for AXS-05 in Alzheimer's Agitation, NDA Submission Planned for 2025

Axsome Therapeutics reports successful completion of its Phase 3 clinical program for AXS-05 in Alzheimer's disease agitation, with the ACCORD-2 trial meeting its primary endpoint and a New Drug Application planned for the second half of 2025.

Summary

• Axsome Therapeutics has completed its Phase 3 clinical program for AXS-05 in Alzheimer's disease agitation.
• The ACCORD-2 trial met its primary endpoint, showing a statistically significant delay in the time to relapse of agitation compared to placebo, with a hazard ratio of 0.276 (p=0.001), indicating a 3.6-fold lower risk of relapse.
• The ACCORD-2 trial also achieved a key secondary endpoint, demonstrating a statistically significant prevention of relapse of agitation compared to placebo (p=0.001).
• AXS-05 reduced the worsening of overall Alzheimer's disease severity compared to placebo in the ACCORD-2 trial (p<0.001).
• The ADVANCE-2 trial did not achieve statistical significance on its primary endpoint, but showed numerically greater improvements with AXS-05 over placebo.
• AXS-05 was well-tolerated in both controlled and long-term trials, with no association with death, increased risk of falls, cognitive decline, or sedation.
• The company plans to submit a New Drug Application (NDA) to the FDA in the second half of 2025.

Sentiment

Score: 8

Explanation: The document presents strong positive results from the ACCORD-2 trial, with statistically significant improvements in key endpoints and a favorable safety profile. The planned NDA submission is also a positive sign. However, the lack of statistical significance in the ADVANCE-2 trial tempers the overall sentiment slightly.

Positives

• The ACCORD-2 trial demonstrated a statistically significant delay in the time to relapse of agitation with AXS-05 compared to placebo.
• AXS-05 showed a 3.6-fold lower risk of relapse compared to placebo in the ACCORD-2 trial.
• AXS-05 significantly prevented relapse of agitation compared to placebo in the ACCORD-2 trial.
• AXS-05 reduced the worsening of overall Alzheimer's disease severity compared to placebo in the ACCORD-2 trial.
• AXS-05 was well-tolerated in both controlled and long-term trials.
• There were no deaths associated with AXS-05 in the clinical program.
• AXS-05 was not associated with increased risk of falls, cognitive decline, or sedation.
• The long-term safety data supports the use of AXS-05 for extended periods.

Negatives

• The ADVANCE-2 trial did not achieve statistical significance on its primary endpoint, although it showed numerical improvements with AXS-05 over placebo.
• The ADVANCE-2 trial showed a reduction in CMAI score of 13.8 points for AXS-05 and 12.6 points for placebo, which was not statistically significant.

Risks

• The ADVANCE-2 trial not achieving statistical significance on its primary endpoint could raise some concerns about the overall efficacy of AXS-05.
• The NDA submission is planned for the second half of 2025, which is subject to regulatory review and approval timelines.
• The company's ability to successfully commercialize AXS-05 depends on regulatory approval and market acceptance.

Future Outlook

Axsome plans to submit a New Drug Application (NDA) to the FDA for AXS-05 in Alzheimer's disease agitation in the second half of 2025.

Management Comments

• Jeffrey Cummings, MD, ScD, stated that agitation is a significant challenge in Alzheimer's disease and that the results of the ACCORD-2 trial are robust and clinically meaningful.
• Herriot Tabuteau, MD, CEO of Axsome Therapeutics, expressed pleasure with the successful completion of the Phase 3 program and the strong results of the ACCORD-2 trial.

Industry Context

This announcement is significant as it addresses a high unmet need in the treatment of Alzheimer's disease agitation, a condition that affects a large proportion of patients and has limited treatment options. The positive results from the ACCORD-2 trial and the planned NDA submission position AXS-05 as a potential new treatment option in this space.

Comparison to Industry Standards

• The ACCORD-2 trial's primary endpoint of delaying time to relapse is a clinically relevant measure, aligning with industry standards for assessing treatments for agitation.
• The use of the Cohen-Mansfield Agitation Inventory (CMAI) and Clinical Global Impression of Severity (CGI-S) scales are standard in clinical trials for Alzheimer's disease agitation.
• The long-term safety data, with over 300 patients treated for at least 6 months and over 100 patients treated for at least 12 months, is robust and exceeds the typical requirements for safety assessments in this therapeutic area.
• The results of the ACCORD-2 trial are particularly notable as they demonstrate a statistically significant benefit in a randomized withdrawal design, which is considered a rigorous approach to assessing maintenance of effect.
• The fact that AXS-05 has demonstrated statistically significant efficacy in three pivotal Phase 3 trials (ADVANCE-1, ACCORD-1, and ACCORD-2) is a strong indicator of its potential as a treatment for Alzheimer's disease agitation. This compares favorably to many other drugs in development that may only have one or two positive trials.

Stakeholder Impact

• Shareholders will likely react positively to the successful completion of the Phase 3 program and the planned NDA submission.
• Patients with Alzheimer's disease agitation and their families may benefit from a new treatment option.
• Healthcare providers will have a new potential therapy to manage agitation in Alzheimer's patients.

Next Steps

• Axsome plans to submit a New Drug Application (NDA) to the FDA for AXS-05 in Alzheimer's disease agitation in the second half of 2025.

Key Dates

Keywords

AXS-05, Alzheimer's disease, agitation, clinical trial, Phase 3, NDA, FDA, dextromethorphan, bupropion, relapse, safety, efficacy