FDA Issues CRL to Lykos for MDMA-Assisted Therapy

BREAKING NEWS

FDA

The US Food and Drug Administration issues a complete response letter (CRL) for Lykos’s midomafetamine (MDMA)-assisted psychotherapy for posttraumatic stress disorder (PTSD), noting it cannot be approved based on the data submitted. The FDA has requested an additional Phase 3 trial examining safety and efficacy. According to a press release, Lykos “plans to request a meeting with the FDA to ask for reconsideration of the decision and to further discuss the agency's recommendations for a resubmission seeking regulatory approval for midomafetamine capsules.”¹

"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, Chief Executive Officer of Lykos Therapeutics, said in a press statement. "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."¹

Already, there are responses expressing disappointment over the decision. Cristina Pearse, a participant in the Phase 3 trial, shared in a letter to the press on August 9, 2024: "I am living proof that MDMA-Assisted Therapy (MDMA-AT) is safe, effective, life-changing, and even life-saving. By not approving MDMA-AT, the FDA is risking the lives of the 13 million Americans suffering from PTSD.” 

Despite attempting other therapies, she did not see relief, but she did in the trial. “In just three sessions, what used to feel like a tsunami of overwhelming panic became merely a puddle at my feet. Most significant was the absolute extinguish of suicidal ideation,” she explained in her letter. “I am disappointed and enraged that the FDA has chosen to prevent millions of other Americans like myself, particularly survivors, from regaining resilience and improving the quality of life that was robbed from them.”

Psychiatric Times editor in chief, John J. Miller, MD, was similarly disappointed in the decision. “Despite 23 years of collaboration between the FDA and Lykos Therapeutics, previously known as MAPS, and despite impressive results in Phase 3 studies demonstrating efficacy in patients with moderate to severe PTSD, the FDA appears to have postpone approval based on a poor understanding of the necessity of the integrated protocol of limited use of MDMA to facilitate well-established psychotherapeutic modalities to synergize and improve symptoms and functioning for individuals whose lives have been upended by moderate to severe PTSD,” he told Psychiatric Times. “This decision will likely set back integrated treatments based on this model, including the extensively studied clinical use of psilocybin, for years and possibly decades. Additionally, non-FDA approved drugs with no Risk Evaluation and Mitigation Strategy component to treatment, already widely used despite being off-label and in many cases illegal, will only increase in use creating more harm.”

The decision comes about a month after the FDA Psychopharmacologic Drugs Advisory Committee voted 9 to 2 against recommending the treatment and pressure from activist groups and some concerned patients on one side concerned about safety and other issues and government officials, veterans, and veteran organizations on the other urging thoughtful consideration for the scientific data for the treatment.²

This process represented a number of firsts in the drug approval process: It is the first time the FDA advisory committee reviewed a psychedelic; it is the first treatment to be considered for PTSD in more than 20 years; it was the first New Drug Application combining a drug and psychotherapy.

Shortly before the approval, on August 1, 2024, Lykos shared they are working on new initiatives and oversights to ensure safety and appropriateness of the psychotherapeutic portion of the treatment. This includes establishing an independent advisory boards, supporting and preparing behavioral institutions for implementation, and collaborating on training clinicians to administer the MDMA-assisted psychotherapy.³

"Given the novelty of this approach, we are taking steps to help ensure additional oversight for this drug plus therapy modality, if FDA approved, and to help integrate into the real-world healthcare setting," Amy Emerson, Chief Executive Officer at Lykos Therapeutics, said in a press statement.³

"Patients [with PTSD] deserve the most effective treatments we can offer, and we want to make sure that we are well positioned to meet their needs," Advisory board member Barbara O. Rothbaum, PhD, professor of psychiatry at Emory University School of Medicine, said in a press statement. "Given the promise of midomafetamine-assisted therapy, we have been preparing our center to be an early leader in this potential science-driven combination treatment."³

References

1. Lykos Therapeutics Announces Complete Response Letter for Midomafetamine Capsules for PTSD. PR Newswire. August 9, 2024. https://www.prnewswire.com/news-releases/lykos-therapeutics-announces-complete-response-letter-for-midomafetamine-capsules-for-ptsd-302219182.html

2. Duerr HA. Officials, Veterans Urge Careful Consideration for MDMA-Assisted Psychotherapy. Psychiatric Times. August 8, 2024. Accessed August 9, 2024. https://www.psychiatrictimes.com/view/officials-veterans-urge-careful-consideration-for-mdma-assisted-psychotherapy

3. Lykos Therapeutics. Lykos Therapeutics Announces New Initiatives and Measures for Additional Oversight for Midomafetamine-Assisted Therapy, if FDA Approved. August 1, 2024. Accessed August 9, 2024. https://news.lykospbc.com/2024-08-01-Lykos-Therapeutics-Announces-New-Initiatives-and-Measures-for-Additional-Oversight-for-Midomafetamine-Assisted-Therapy,-if-FDA-Approved