FDA rejects MDMA-assisted PTSD therapy, requests additional data

Key takeaways:

• The FDA has requested an additional phase 3 trial to further study the safety and efficacy of MDMA for PTSD.
• Lycos plans to ask the FDA for more guidance on resubmitting the application.

The FDA on Aug. 9 issued a complete response letter to Lycos Therapeutics for its new drug application regarding midomafetamine capsules for the treatment of PTSD, citing insufficient data to approve and requesting an additional phase 3 trial.

According to a Lycos press release, the company plans to request a meeting with the agency, seeking reconsideration of its ruling and to discuss recommendations for resubmission of the application, which states that midomafetamine (MDMA) would be used in combination with a psychological intervention.

“The FDA request for another study is deeply disappointing, not just for all those who dedicated their lives to this pioneering effort, but principally for the millions of Americans with PTSD, along with their loved ones, who have not seen any new treatment options in over two decades,” Amy Emerson, Lycos CEO, said in the release. “While conducting another phase 3 study would take several years, we still maintain that many of the requests that had been previously discussed with the FDA and raised at the advisory committee meeting can be addressed with existing data, post-approval requirements or through reference to the scientific literature.”

The day after the FDA issued its complete response letter, the journal Psychopharmacology retracted three papers related to the use of MDMA for PTSD. According the journal’s retraction notices, the decision was made due to “protocol violations amounting to unethical conduct” at one of the study sites. The editors also wrote that the study authors were aware of the violations upon manuscript submission but chose to neither disclose their knowledge nor remove potentially compromised data.

The misconduct allegations were discussed during the FDA’s Psychopharmacologic Drugs Advisory Committee meeting in June. As previously reported, committee members voted against Lycos’ application. Specifically, when asked whether the available data showed that MDMA-assisted psychotherapy is effective in patients with PTSD, nine members voted “no” and two members voted “yes.” When asked whether the benefits of MDMA-assisted psychotherapy outweigh its risks, 10 members voted “no” and one voted “yes.”

In its ruling, the committee cited insufficient data and concerns over the alleged misconduct during clinical trials, gaps in data and diversity of the study population, as well as inconsistencies in the proposed psychological intervention. However, some committee members said that MDMA-assisted therapy still represents a promising path forward.

After the committee meeting, Lycos issued a response, touting evidence of its effectiveness, the company’s effort to minimize the impact of functional unblinding, as well as intent to regulate the psychological intervention provided with MDMA, if approved.

References:

• Lykos Therapeutics statement on FDA Advisory Committee meeting. https://news.lykospbc.com/2024-06-13-Lykos-Therapeutics-Statement-on-FDA-Advisory-Committee-Meeting. Published June 13, 2024. Accessed Aug. 12, 2204.
• Jerome L, et al. Psychopharmacol. 2024;doi:10.1007/s00213-020-05548-2.
• Feduccia AA, et al. Psychopharmacol. 2024:doi:10.1007/s00213-024-06671-0.
• Mithoefer MC, et al. Psychopharmacol. 2024:doi:10.1007/s00213-024-06666-x.