8-K: Axsome Therapeutics Announces Mixed Results from Phase 3 Trial of Solriamfetol in Major Depressive Disorder

Axsome Therapeutics' Phase 3 PARADIGM trial of solriamfetol in MDD showed no statistically significant improvement in the overall patient population, but demonstrated promising results in a subgroup with severe excessive daytime sleepiness (EDS), leading to plans for a Phase 3 trial in MDD patients with EDS.

Summary

• Axsome Therapeutics announced the results of its PARADIGM Phase 3 proof-of-concept trial of solriamfetol in major depressive disorder (MDD) with and without severe excessive daytime sleepiness (EDS).
• The study did not demonstrate a statistically significant change on the Montgomery-sberg Depression Rating Scale (MADRS) total score compared to placebo in the overall patient population.
• However, in the prespecified subgroup of patients with severe EDS, treatment with solriamfetol resulted in greater improvements in depressive symptoms compared to placebo.
• The study was a 6-week, randomized, double-blind, placebo-controlled, multicenter, U.S. trial.
• MDD patients with severe EDS (n=51) and without severe EDS (n=295) were randomized to treatment with solriamfetol 300 mg or placebo.
• In MDD patients with severe EDS (ESS score 16), solriamfetol treatment resulted in clinically meaningful and numerically greater improvements compared to placebo on multiple efficacy measures at Week 6.
• Axsome plans to initiate a Phase 3 trial in MDD patients with EDS in 2025.
• Solriamfetol was safe and well tolerated in the trial, with a side effect profile consistent with its established safety profile.

Sentiment

Score: 5

Explanation: The sentiment is neutral. While the overall trial failed to meet its primary endpoint, there were positive signals in the EDS subgroup, warranting further investigation. The company is proceeding with a Phase 3 trial, indicating some confidence in the drug's potential.

Positives

• Solriamfetol showed promising results in MDD patients with severe EDS, with clinically meaningful and numerically greater improvements compared to placebo on multiple efficacy measures.
• Solriamfetol was safe and well tolerated in the trial, with a side effect profile consistent with its established safety profile.
• Axsome plans to initiate a Phase 3 trial in MDD patients with EDS in 2025, indicating continued development and potential for approval in this specific patient population.

Negatives

• The PARADIGM Phase 3 trial did not meet its primary endpoint in the overall patient population of MDD patients with and without severe EDS.
• The study was not powered to demonstrate statistical significance in the prespecified subgroups, which limits the strength of the findings in the EDS subgroup.

Risks

• The planned Phase 3 trial in MDD patients with EDS may not be successful.
• Regulatory approval for solriamfetol in MDD with EDS is not guaranteed.
• The market acceptance of solriamfetol for MDD with EDS, if approved, is uncertain.

Future Outlook

Axsome plans to initiate a Phase 3 trial in MDD patients with EDS in 2025 based on the promising results observed in the EDS subgroup of the PARADIGM trial.

Management Comments

• Herriot Tabuteau, MD, Chief Executive Officer of Axsome Therapeutics, said, 'We are pleased to have completed the PARADIGM trial which provides data on the potential utility of solriamfetol in patients with MDD.'
• He also stated, 'The promising results with solriamfetol in MDD patients with severe EDS align with its known pharmacology and support its further evaluation in this potentially new indication.'

Industry Context

The announcement highlights the unmet need for therapies to treat MDD with EDS, a condition affecting approximately 50% of MDD patients. Axsome is positioning solriamfetol as a potential treatment option for this specific patient population.

Comparison to Industry Standards

• Currently, no therapies are approved to treat MDD with EDS, making solriamfetol a potential first-in-class treatment if approved.
• Other companies developing treatments for MDD include Eli Lilly (Prozac, Cymbalta), Pfizer (Zoloft), and GlaxoSmithKline (Paxil), but these treatments do not specifically target EDS in MDD patients.
• The efficacy of solriamfetol in the EDS subgroup will need to be confirmed in a larger, statistically powered Phase 3 trial to meet regulatory standards for approval.

Stakeholder Impact

• Shareholders may react positively to the plan to initiate a Phase 3 trial in MDD patients with EDS, but negatively to the failure of the overall trial to meet its primary endpoint.
• Patients with MDD and EDS may benefit from the development of a new treatment option.
• Employees of Axsome Therapeutics will be involved in the planning and execution of the Phase 3 trial.

Next Steps

• Initiate a Phase 3 trial in MDD patients with EDS in 2025.
• Present full results of the PARADIGM trial at future scientific conferences.

Key Dates

Keywords

Solriamfetol, MDD, EDS, Major Depressive Disorder, Excessive Daytime Sleepiness, Phase 3 Trial, Axsome Therapeutics, PARADIGM, CNS Disorders