Lykos Therapeutics’ midomafetamine (MDMA) treatment for post-traumatic stress disorder (PTSD) has suffered another setback after the US Food and Drug Administration (FDA) refused to approve the therapy.

On 9 August, Lykos said, the US regulatory agency issued a complete response letter (CRL) stating that the MDMA therapy “could not be approved based on data submitted to date” and asked Lykos to conduct another Phase III trial. The US-based company plans to ask the US FDA to reconsider its negative decision.

The FDA rejection was foreshadowed by the negative opinion issued by the FDA’s Psychopharmacologic Drugs Advisory Committee (AdCom) in June. In a 9-2 vote, the AdCom found that available data did not show MDMA’s efficacy in PTSD. The panel also voted 10-1, stating that the benefits of the drug do not outweigh its risks.

Lykos questions however whether the AdCom properly considered the company’s candidate. In a press release, Lykos noted that “the company and other stakeholders have expressed concerns around the structure and conduct of the AdCom meeting, including the limited number of subject matter experts on the panel and the nature of the discussion, which at times veered beyond the scientific content in the briefing documents.”

The company plans to request a meeting with the FDA to discuss resubmission of MDMA’s new drug application (NDA). Amy Emerson, chief executive officer of Lykos said: “While conducting another Phase III 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."

Lykos presented positive data from two Phase III trials at the FDA AdCom meeting - MAPP1 (NCT03537014) and MAPP2 (NCT04077437). The AdCom raised concerns regarding the trial design, especially regarding functional blinding. Lykos noted in a response letter that it took steps to minimise the impact of functional blinding and “the weight of evidence suggests a very low likelihood that the observed MDMA effect can be adequately explained by functional unblinding”.

Psychedelics such as MDMA have emerged as a new treatment option in recent years. Multiple companies are trialling these therapies. Furthermore, the US FDA released its first-ever draft guidance on clinical trials investigating psychedelic drugs in June 2023.