ASCEND Phase 2 Study

Primary Endpoint: LS mean change from baseline in the MADRS total score, calculated at each time point and averaged (overall
treatment effect).^1,2

Select secondary endpoint: Percentage of patients achieving MADRS total score of ≤10 at Week 2 (protocol-defined remission).²

Efficacy assessments were performed at weeks 1, 2, 3, 4 and 6 on the mITT population (N=80). The mITT population was defined as all randomized patients who took at least 1 dose of study drug, had at least 1 post-baseline assessment, and whose diagnosis and severity of MDD were confirmed, based on clinical review, by an independent assessor who was blinded to treatment assignment. A total of 17 randomized subjects were excluded from the mITT by the independent assessor.²

The MADRS is a clinician-rated scale used to assess depressive symptom severity. Patients are rated on 10 items to assess feelings of sadness, inner tension, reduced sleep or appetite, difficulty concentrating, lassitude, lack of interest, pessimism, and suicidality. Scores range from 0 to 60, with higher scores indicating more severe depression.¹

Key inclusion criteria: male or female 18 to 65 years of age; DSM-5 criteria for current MDD without psychotic features; MADRS total score ≥25; and CGI-S score ≥4 at baseline.²

Key exclusion criteria: bipolar disorder, panic disorder, obsessive-compulsive disorder, treatment-resistant depression (defined as ≥2 failed adequate antidepressant treatments in the current major depressive episode), substance use disorder within the past year, lifetime history of psychotic disorder, clinically significant risk of suicide, and history of seizure disorder.²

Demographics and Baseline Characteristics

• Demographic and baseline disease characteristics were similar across both treatment groups.²
• Patients had a median age of 36 years (range 18 to 64 years), and were 64% female, 63% White, 33% Black, and 1% Asian.^2,3
• At baseline for AUVELITY and bupropion SR groups, mean MADRS total score was 31.8 and 32.2, respectively.²

Footnotes and Definitions

BID=twice a day; CGI-S=Clinical Global Impression-Severity; DSM-5=Diagnostic and Statistical Manual of Mental Disorders, 5th Edition; LS=least squares; MADRS=Montgomery-Åsberg Depression Rating Scale; MDD=major depressive disorder; mITT=modified intention-to-treat; SR=sustained-release.

References

1. AUVELITY [Prescribing Information]. Axsome Therapeutics, Inc.: New York, NY.
2. Tabuteau H, Jones A, Anderson A, Jacobson M, Iosifescu DV. Effect of AXS-05 (dextromethorphan-bupropion) in major depressive disorder: a randomized double-blind controlled trial. Am J Psychiatry. 2022;179(7):490-499.
3. Data on File. Axsome Therapeutics, Inc. DOF-AUV-00509.