Experts Endorse MDMA-assisted Therapy for PTSD

Rationale: Efficacy

The phase 3 clinical trials of midomafetamine-assisted therapy for PTSD have shown substantial evidence of efficacy with a consistency of results across the fifteen different study sites and across various patient subgroups that provides additional confidence in the reliability of the primary finding.

Although concerns have been raised about functional unblinding and expectancy effects in the phase 3 trials, these are common issues with testing psychoactive medications. We believe that these concerns do not rise to a level that would call the main clinical trial findings into question. In our assessment, the findings provide ample evidence of the efficacy of midomafetamine-assisted therapy for PTSD:

• CAPS-5 Score Improvements in Patients with PTSD: The phase 3 trials have demonstrated a clinically meaningful reduction in PTSD symptoms, as measured by CAPS-5 (Clinician-Administered PTSD Scale for DSM-5) scores, in participants with moderate to severe PTSD who received midomafetamine-assisted therapy compared to those who received placebo plus therapy. The reduction was statistically significant with substantial evidence of efficacy. At the primary study endpoint across two phase 3 trials, 87% of participants in the midomafetamine group experienced a clinically meaningful response, 69% no longer met the diagnostic criteria for PTSD, and 40% achieved remission. In contrast, 66% of participants in the placebo-plus-therapy group had a clinically meaningful response, 41% did not meet diagnostic criteria, and 14% achieved remission. The CAPS-5 was administered by remote, blinded, independent assessors.
  

  On average, participants in the midomafetamine group experienced approximately a two-fold greater reduction in CAPS-5 scores compared to the placebo-plus-therapy group.

• Durable Remission of PTSD Symptoms:Long-term follow-up data from both phase 3 studies suggest that remission persists for at least 6 months after the treatment, with 39% of the midomafetamine group still in remission, compared to 11% of the placebo- plus-therapy group. This is a particularly notable finding given that patients in both studies had suffered from PTSD for an average of 15 years.
• Additional Improvements in Patients: Improvements were also observed in the key secondary endpoint – scores on the Sheehan Disability Scale (SDS), including reductions in functional impairment associated with PTSD, as well as exploratory endpoints of depression symptoms, as measured by the Beck Depression Inventory (BDI-II). The midomafetamine-assisted therapy group showed significantly greater reductions in both SDS and BDI-II scores compared to the placebo-plus-therapy group.

Conclusion

While we agree with many of the issues raised by the FDA advisory committee, given the data we have reviewed and the urgency of the need, our assessment is that the benefits of midomafetamine-assisted therapy outweigh the risks and that midomafetamine is now approvable. The use of midomafetamine-assisted therapy should include a Risk Evaluation and Mitigation Strategy (REMS) that can be adjusted as real-world safety and efficacy data emerge.