FDA Committee Votes Against Approval of Lykos Therapeutics’ MDMA Treatment for PTSD

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The FDA’s Psychopharmacologic Drug Advisory Committee (PDAC) has voted against recommending Lykos Therapeutics’ New Drug Application (NDA) for midomafetamine (MDMA) capsules for use in combination with psychological intervention for the treatment of post-traumatic stress disorder (PTSD) in adults. The committee voted 2-to-9 against the efficacy of the treatment, and voted 1-to-10 against the benefits outweighing the risks, stating its doubts that MDMA-assisted therapy is effective in treating PTSD.¹

"We are disappointed in today's vote given the urgent unmet need in PTSD and appreciate that the committee faced a challenging and atypical assignment, which was to evaluate a therapeutic approach that combines drug therapy (MDMA) and psychological intervention," said Amy Emerson, CEO, Lykos Therapeutics, in a press release.

As a basis of their review, PDAC evaluated the data from the randomized, double-blind, placebo-controlled, Phase III MAPP1 and MAPP2 trials evaluating the efficacy and safety of MDMA used in combination with psychological intervention.¹

The MAPP1 study evaluated the safety and efficacy of the combination versus a placebo in treating adults with PTSD. According to the results, 88% of those treated with MDMA had a meaningful improvement in PTSD symptoms, with 67% no longer considered suffering from PTSD as a result, compared to 32% in the placebo group.

Common adverse events (AEs) from MDMA treatment included muscle tightness, decreased appetite, nausea, sweating, pupil dilation, and feeling cold, with no serious AEs reported. The MAPP2 study had two key differences from MAPP1. As part of MAPP2, patients with both moderate and severe PTSD were enrolled, whereas MAPP1 only enrolled those with severe PTSD. Further, patients of color represented approximately more than 50% of the study.^2,3

According to a report by NPR, several PDAC members voiced their concerns regarding bias with potential misconduct that had the potential to manipulate the results of the studies. Additionally, the committee said that there were a number of unanswered questions regarding the treatment’s potential abuse, data gaps, and minimal evidence that supports the benefit of the psychological approach used in therapy sessions. Despite attempts by Lykos to blind patients as to whether they received MDMA or placebo, it was reported that many patients were aware of whether they were administered MDMA or placebo, with the committee suggesting that this led to further bias.³

Strong support for approval has come from a number of trial participants, with some finding the treatment to be a significant improvement when it comes to getting better sleep, relationships, and an improved quality of life. However, some researchers have criticized Lykos, believing that a number of AEs were not reported. One participant made a public comment to the FDA, suggesting that her therapist encouraged her to view worsening symptoms as a sign of progress as opposed to getting better. She also added that multiple trial participants began feeling suicidal after the trial had ended, according to the NPR report.³

Despite the FDA not being bound by PDAC's vote, it is taken into serious consideration. A final decision is expected per the agency’s Prescription Drug User Fee Act target date of August 11, 2024.¹

"We remain committed to working with the FDA to address outstanding questions so that we may find a path forward to ensure the responsible and careful introduction of MDMA-assisted therapy into the healthcare system, if approved,” said Emerson, in the press release. “We are grateful to the advocates, clinical trial participants and people living with PTSD who shared their testimony in the open public hearing and through written comments and will continue to do everything we can to bring this potential new therapeutic option to people living with PTSD."

References

1. Lykos Therapeutics Provides Update on FDA Advisory Committee Meeting for Investigational MDMA-Assisted Therapy for PTSD. Lykos Therapeutics. June 4, 2024. Accessed June 5, 2024. https://news.lykospbc.com/2024-06-04-Lykos-Therapeutics-Provides-Update-on-FDA-Advisory-Committee-Meeting-for-Investigational-MDMA-Assisted-Therapy-for-PTSD

2. MAPS PBC Completes Second Phase 3 "MAPP2" Trial of MDMA-Assisted Therapy for Treatment of PTSD. Lykos Therapeutics. November 17, 2022. Accessed June 5, 2024. https://news.lykospbc.com/2022-11-17-MAPS-PBC-Completes-Second-Phase-3-MAPP2-Trial-of-MDMA-Assisted-Therapy-for-Treatment-of-PTSD

3. FDA advisors reject MDMA therapy for PTSD, amid concerns over research. NPR. June 4, 2024. Accessed June 5, 2024. https://www.npr.org/sections/shots-health-news/2024/06/04/nx-s1-4991112/mdma-therapy-ptsd-fda-advisors