AXSM
Axsome Therapeutics, INC
NASDAQ
8-K: Axsome Therapeutics Announces Positive Phase 3 Results for AXS-05 in Alzheimer's Agitation, NDA Submission Planned for 2025
Sentiment:
Clinical Trial Results
30 December 2024 7:56 AM
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.
Better than expected
The ACCORD-2 trial met its primary endpoint with a statistically significant result, demonstrating a 3.6-fold lower risk of relapse compared to placebo, which is better than expected.
The ACCORD-2 trial also met its key secondary endpoint, showing statistically significant prevention of relapse of agitation, which is better than expected.
AXS-05 reduced the worsening of overall Alzheimer's disease severity compared to placebo in the ACCORD-2 trial, which is better than expected.
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
- June 2020: AXS-05 was granted U.S. FDA Breakthrough Therapy designation for the treatment of Alzheimer's disease agitation.
- December 30, 2024: Axsome Therapeutics issued a press release announcing the results of its ADVANCE-2 and ACCORD-2 trials and hosted a conference call to discuss the results.
Keywords
AXS-05, Alzheimer's disease, agitation, clinical trial, Phase 3, NDA, FDA, dextromethorphan, bupropion, relapse, safety, efficacy
AXSM
Axsome Therapeutics, INC
NASDAQ
Sector: TBD
Filings with Classifications
Delay expected
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Regulatory Update
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Worse than expected
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Regulatory Update
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Capital raise
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- The gross proceeds from the private placement were approximately $15 million.
- Purchasers agreed to a lock-up period of 120 days from the closing date, restricting the sale or transfer of the securities.
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Quarterly Report
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Capital raise
5 May 2025 4:47 PM
Quarterly Report
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Delay expected
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Quarterly Report
- If Subtenant is delayed in completing the New Premises Subtenant Work and vacate the Original Premises within four (4) months of the New Premises Commencement Date, subject to Force Majeure, then, notwithstanding anything to the contrary contained herein, Subtenant shall not be required to pay holdover rent as set forth in Section 3 above for the amount of time that Prime Landlords actions delayed Subtenant in completing the New Premises Subtenant Work (such amount of time, the Prime Landlord Delay) and the Original Premises Termination Date shall be extended by such period of Prime Landlord Delay; provided however that maximum amount of time for the delay in Subtenant paying holdover rent pursuant to Section 3 hereof shall be an additional thirty (30) days so that if Subtenant has not vacated the Original Premises and delivered possession of the Original Premises to Sublandlord due to Prime Landlord Delay within five (5) months of the New Premises Commencement Date, for whatever reason whatsoever, Subtenant shall pay such holdover rent pursuant to Section 3 hereof.
Better than expected
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Quarterly Report
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Press Release
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Better than expected
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Clinical Trial Results
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Capital raise
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Annual Results
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Better than expected
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Annual Results
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Annual Results
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Better than expected
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Press Release
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Better than expected
30 December 2024 7:56 AM
Clinical Trial Results
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- The ACCORD-2 trial also met its key secondary endpoint, showing statistically significant prevention of relapse of agitation, which is better than expected.
- AXS-05 reduced the worsening of overall Alzheimer's disease severity compared to placebo in the ACCORD-2 trial, which is better than expected.
Better than expected
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Clinical Trial Results
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Capital raise
12 November 2024 9:43 AM
Quarterly Report
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Worse than expected
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Quarterly Report
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Better than expected
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Quarterly Report
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Better than expected
1 October 2024 5:24 PM
Loan Agreement Amendment
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Capital raise
5 August 2024 4:30 PM
Quarterly Report
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Worse than expected
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Quarterly Report
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Quarterly Report
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Delay expected
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Worse than expected
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Quarterly Report
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Capital raise
6 May 2024 5:20 PM
Quarterly Report
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Worse than expected
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Quarterly Report
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Patient Survey Results Announcement
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Better than expected
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Clinical Trial Results
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Delay expected
20 February 2024 7:05 AM
Annual Results
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Better than expected
20 February 2024 7:05 AM
Annual Results
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