Lykos CEO Addresses MDMA Efficacy and Safety Concerns Amid Expanding Debate

A week after the FDA's Psychopharmacologic Drugs Advisory Committee (PDAC) declined to endorse a midomafetamine (MDMA) treatment for post-traumatic stress disorder (PTSD), Lykos Therapeutics is working to address public concerns about its therapy. This initiative follows the committee's vote against MDMA capsules due to questions regarding their efficacy and safety. Although the FDA is not obligated to follow the PDAC's guidance, it typically does. Consequently, the topic has stirred significant public discourse.

Lykos CEO Amy Emerson has written to shareholders to clarify the company's stance on midomafetamine, which is currently under FDA review for PTSD treatment. She acknowledged that the PDAC meeting highlighted several issues that have since become a focal point of public dialogue. Emerson emphasized the importance of sharing the company's perspectives on these concerns.

In her letter, Emerson highlighted the company's confidence in its MDMA application, which is supported by two randomized, placebo-controlled phase 3 clinical trials. Both studies demonstrated statistically significant, clinically meaningful improvements in PTSD symptoms compared to the control group. However, the committee raised concerns about whether clinical investigators and patients could distinguish between the study drug and the placebo. Emerson acknowledged this as a known challenge but noted that Lykos had taken numerous steps to mitigate its impact. These measures included using independent, blinded third-party clinician raters to assess outcomes.

The committee also questioned whether patients with prior illicit MDMA use could be biased. Emerson reported no significant differences in primary outcome measures between those who had used street MDMA and those who had not. Another primary concern was the use of MDMA-assisted therapy, which involves administering the drug alongside talk therapy. While one committee member noted this as a significant strength, they also saw it as a liability since the FDA does not regulate the therapy component. Emerson assured that steps were taken to standardize the therapy during the trial and clarified that psychotherapy is already a regulated field.

Lykos plans to implement a Risk Evaluation and Mitigation Strategy (REMS) program to ensure the benefits of MDMA therapy outweigh its risks. However, the committee did not fully examine the REMS program because its complete requirements are still under development.

Emerson also addressed a serious incident from a 2015 phase 2 trial involving therapist misconduct, which involved a case of sexual abuse between a therapist and a patient. The therapists involved were banned from future work with the company, and Lykos reported the incident to Health Canada, the FDA, and the relevant review board. Committee member Walter Dunn, M.D., Ph.D., repeatedly raised the issue to understand how to prevent similar incidents in the future. Patient advocate Elizabeth Joniak-Grant, Ph.D., emphasized the need to be explicit about the nature of the misconduct, given the vulnerability of PTSD patients to sexual violence.

Lykos has enacted new policies to prevent and detect misconduct and unethical behavior, including independent reporting channels. These measures will be expanded if midomafetamine is approved. The company also addressed concerns about sponsor and investigator bias, particularly regarding the failure to collect data on feelings of euphoria, which could inform the drug's addiction potential. Lykos, which rebranded from MAPS PBC at the end of 2023, dismissed these concerns.

The FDA committee also raised questions about potential cardiovascular and liver toxicity risks associated with MDMA. Emerson committed to collaborating with the FDA to clarify existing data or gather new information on these risks as required.

In closing, Emerson reiterated Lykos' commitment to working with the FDA, which will ultimately decide if MDMA is ready for market approval. "Misinformation has been circulated about our program, and we want to clarify that the FDA has received all data and supporting documentation," Emerson wrote.