FDA Rejects MDMA-Assisted Therapy for PTSD

The FDA declined to approve midomafetamine (MDMA) as an adjunct to psychotherapy for post-traumatic stress disorder (PTSD), calling for additional data, developer Lykos Therapeutics announced on Friday.

“The FDA has requested that Lykos conduct an additional Phase 3 trial to further study the safety and efficacy of midomafetamine,” the company said. “Lykos plans to request a meeting with the FDA to ask for reconsideration of the decision and to further discuss the agency’s recommendations for a resubmission seeking regulatory approval for midomafetamine capsules.”

The hotly anticipated decision came after a negative review by an FDA advisory committee in June, where the majority of members voted against the drug for approval citing an imbalance of risk and benefit for the first-in-class treatment.

FDA reviewers listed concerns with cardiac safety including significant increases in blood pressure and pulse, which could potentially trigger cardiovascular events. There were also additional safety concerns, including prolonged impairment and vulnerability or potential for abuse.

Following a similarly negative sentiment, a March report from the Institute for Clinical and Economic Review (ICER) rated the publicly available trial data on MDMA-assisted therapy “insufficient.”

Just a few days ago, over 60 bipartisan lawmakers penned a letter to the Biden administration urging approval describing a “grave need for new and better treatment options like MDMA-assisted therapy” for Veterans and service-members. The condition affects an estimated 5% of the U.S. population in any given year, according to the Veterans’ Administration National Center for PTSD, but is more prevalent among military personnel.

Midomafetamine would have been the first new PTSD therapy in over two decades. The selective serotonin reuptake inhibitors (SSRIs) sertraline (Zoloft) and paroxetine (Paxil) are currently the only treatments to hold indications for PTSD. However, it has been shown that usually less than 20% to 30% of patients achieve full remission on those treatments.

Both of the phase III supporting clinical trials conducted by Lykos met their primary endpoints of a significant improvement in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) score. The participants received three dosing sessions of MDMA with additional psychological support sessions before and after dosing.

In MAPP1, the MDMA and psychotherapy group saw an average drop in CAPS-5 score of 24.4 points compared with an average drop of 13.9 points in those receiving psychotherapy alone. By the end of the third experimental session, 30% of the MDMA group achieved PTSD remission, 60% achieved a loss of diagnosis, and 80% of the group were considered responders to treatment. On the other hand, less than 5% of the psychotherapy-only group achieved PTSD remission, with only half responding to treatment.

MAPP2 reported similar findings, with an average 23.7-point reduction in CAPS-5 score in MDMA-treated patients compared with a reduction of 14.8 points in the psychotherapy-only group. In both trials, patients taking MDMA also achieved the prespecified secondary endpoints.