AXS-05 Safety, Tolerability in Major Depressive Disorder Confirmed in Pooled Analysis of GEMINI and ASCEND Trials
Pooled data from the pivotal randomized clinical trials were consistent with prior outcomes supporting early occurrence and resolution of the most common TEAEs.
Pooled data from the GEMINI and ASCEND randomized controlled clinical trials demonstrated that adverse events associated with AXS-05 (Auvelity; Axsome Therapeutics), an oral NMDA receptor antagonist with multimodal activity indicated for the treatment of major depressive disorder (MDD), were consistent with previously reported trials. The findings were presented at the 30th Nevada Psychiatric Association National Psychopharmacology Update, being held February 12-15, in Las Vegas, NV.
©asxome
The most common treatment-emergent adverse events (TEAEs) were dizziness (17.1%), nausea (13.8%), and headache (8.1%). Most occurred within the first week of treatment and resolved within a median duration of 2.5 to 16 days. The absolute prevalence of these TEAEs ranged from 1.8% to 6.1%, according to developer Axsome.
MDD is a debilitating condition and affects approximately 1 in 5 individuals in the United States. Despite numerous available ADTs, many patients experience significant and enduring side effects, leading 25% to discontinue treatment, prompting Axsome to assess the safety and efficacy of its therapy on a broader scale. The objective of the current pooled analysis was to better understand the onset, duration, and prevalence of TAES.
The GEMINI (Phase 3) and ASCEND (Phase 2) trials were double-blind, randomized controlled studies evaluating the efficacy, tolerability, and safety of AXS-05 compared to active control bupropion or placebo in participants with moderate to severe MDD. In both studies the dextromethorphan-bupropion combination was well tolerated with generally manageable adverse events and low study discontinuation rates, according to the poster presentation.
Participants in GEMINI were randomly assigned to receive AXS-05 or placebo and in ASCEND to receive AXS-05 or bupropion over a 6-week period. The pooled analysis included 327 participants from the GEMINI trial and 80 participants from the ASCEND trial. Demographic characteristics were comparable across treatment groups, with a mean age of approximately 41 years and a balanced representation of sexes and races.
Key Findings
- Efficacy: AXS-05 demonstrated significant improvement in depressive symptoms, as measured by the Montgomery-Åsberg Depression Rating Scale, with consistent efficacy across different subgroups (sex, race, prior ADT use).
- Safety: The most common TEAEs were dizziness, nausea, and headache. Most TEAEs occurred within the first week of treatment and resolved within a median duration of 2.5 to 16 days. The absolute prevalence of these TEAEs ranged from 1.8% to 6.1%.
- Prevalence of other TAES were: diarrhea (2.3%), dry mouth (3.4%), anxiety (1.9%), somnolence (2.1%), sexual dysfunction (1.8%), and decreased appetite (3.7%).
- More TEAE onsets occurred during the first week of treatment vs each subsequent week, except for sexual dysfunction. More onsets also occurred during the first 7 days of treatment compared to all subsequent days together for each TEAE except for sexual dysfunction. For the latter, Axsome reported 2 events with onset during the first week and 5 with onset during the second week.
- Tolerability: AXS-05 was generally well-tolerated, with low rates of discontinuation due to adverse events.
Conclusion
The pooled data from the GEMINI and ASCEND trials support the efficacy and safety of AXS-05 in treating MDD. The early occurrence and resolution of common TEAEs, along with consistent efficacy across diverse patient demographics, highlight the potential of AXS-05 as a valuable treatment option for MDD.
