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December 12, 2023

MAPS Public Benefit Corporation has submitted a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) for midomafetamine capsules (MDMA) used in combination with psychotherapy for individuals with posttraumatic stress disorder (PTSD). If approved, this would be the first official psychedelic-assisted therapy.

The NDA submission included results from multiple studies including two randomized, double-blind, placebo-controlled Phase 3 studies, MAPP1 and MAPP2, which evaluated the efficacy and safety of MDMA-assisted therapy versus placebo with therapy in participants diagnosed with PTSD. Both MAPP1 and MAPP2 studies met their primary and secondary endpoints In both MAPP1 and MAPP2, the primary endpoint was measured by the change from baseline in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and the key secondary endpoint was improvement in functional impairment associated with PTSD as measured by the change from baseline in the Sheehan Disability Scale (SDS).

Phase 3 Results

The MAPP1 study enrolled patients with severe PTSD. Participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. Study results showed that MDMA significantly reduced PTSD symptoms, as shown by the change in CAPS-5 total severity score from baseline to 18 weeks compared with placebo (p < 0.0001, d = 0.91) and to significantly decrease the SDS total score (p = 0.0116, d = 0.43). The mean change in CAPS-5 scores from baseline to 18 weeks in participants completing treatment was -24.4 (SD 11.6; n = 42) in the MDMA-assisted therapy group and -13.9 (SD 11.5; n = 37) in the placebo with therapy group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. Common adverse events included muscle tightness, decreased appetite, nausea, sweating, pupil dilation, and feeling cold.

MAPP2 was a randomized, double-blind, placebo-controlled Phase 3 study assessing the efficacy and safety of MDMA-assisted therapy versus placebo with therapy in participants diagnosed with moderate or severe PTSD. Participants were randomized to MDMA-assisted therapy (n = 53) or placebo with therapy (n = 51). Study results showed that MDMA significantly reduced PTSD symptoms, as shown by the change in CAPS-5 total severity score from baseline to 18 weeks (p < 0.001, d = 0.7) and to significantly decrease the SDS total score (p = 0.03, d = 0.4). The reduction in CAPS-5 total severity score from baseline to 18-weeks showing a least-squares mean (95% confidence interval [CI]) change of -23.7 (-26.94, -20.44) for MDMA-assisted therapy versus -14.8 (-18.28, -11.28) for placebo with therapy. MDMA-assisted therapy also significantly reduced clinician-rated functional impairment as measured by a reduction in modified SDS from baseline to 18-weeks resulting in a least-squares mean (95% CI) change of –3.3 (-4.03, -2.60) for MDMA-assisted therapy and -2.1 (-2.89, -1.33) for placebo with therapy. Seven participants had a severe treatment emergent adverse event (MDMA-assisted therapy, n = 5 (9.4%); placebo with therapy, n = 2 (3.9%)). There were no deaths or serious treatment emergent adverse event.

The FDA has 60 days to determine whether the NDA will be accepted for review and whether it will be fast-tracked through the approval process. If the FDA approves MDMA for this purpose, it would need to be rescheduled, MAPS says. It's currently a Schedule I drug under the Controlled Substances Act, which the U.S. Drug Enforcement Administration defines as having no currently accepted medical use.

>> MAPS Public Benefit Corporation Press Release

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