The FDA has raised concerns about the safety and efficacy data for Lykos Therapeutics' midomafetamine capsules (MDMA) in treating post-traumatic stress disorder (PTSD), issuing a Complete Response Letter (CRL) on August 9, 2024. This decision underscores the challenges in developing psychedelic drugs for mental health conditions, despite their potential benefits.
FDA's Concerns and Expert Opinions
Fran Brown, SVP, drug development science, Certara, noted that the FDA's concerns included questions about efficacy and significant safety gaps. Functional unblinding in clinical trials, where over 90% of patients could identify whether they were receiving a placebo or active treatment, was a major issue. According to Brown, this knowledge can significantly affect behavior, making well-blinded, placebo-controlled studies crucial for unbiased efficacy, especially in central nervous system disorders.
The FDA also questioned the duration of the drug's effect, as the extension study started long after the initial phase, with many patients already aware of their treatment. This delay compromised the integrity of the long-term data.
FDA Guidelines for Psychedelic Drug Research
In June 2023, the FDA issued draft guidelines for researchers investigating psychedelic drugs for psychiatric or substance use disorders. These guidelines emphasize the need for comprehensive chemistry, manufacturing, and control information to ensure the quality and purity of investigational drugs. Tiffany Farchione, MD, director, division of psychiatry, FDA Center for Drug Evaluation and Research, highlighted the importance of addressing the unique challenges in designing psychedelic drug development programs to yield interpretable results.
Risks and Benefits of Psychedelic Therapy
A 2015 study in the National Library of Medicine suggested that psychedelic medicine might be economically viable due to its relatively time-limited interventions compared to long-term pharmacotherapeutic treatments. The study also noted a favorable safety profile in controlled settings. However, it also highlighted risks such as precipitating psychotic breaks in predisposed individuals and the potential for hallucinogen persisting perception disorder (HPPD), also known as flashbacks.
The Importance of Combination Therapy
Experts like Emily Hartwell, PhD, assistant professor, psychiatry, Hospital of the University of Pennsylvania, stress the importance of combining psychedelic drugs with psychotherapy, similar to traditional antidepressant treatments. Carl Marci, MD, chief clinical officer, OM1, believes this combination is vital for the success of MDMA therapy. Dismantling studies may later explore individual components of psychotherapy protocols to optimize treatment.
Marci also raised concerns about the costs of therapy and medication, as well as insurance reimbursements, emphasizing that understanding the psychotherapy component is crucial for the long-term success of MDMA therapy.
Despite the challenges and the FDA's cautious approach, experts remain optimistic about the potential of MDMA therapy, provided that rigorous research and safety measures are in place.
