FDA Issues Complete Response Letter for MDMA-Assisted Therapy for PTSD

This is an excerpt of a story that first appeared on American Journal of Managed Care.

The FDA has issued a complete response letter (CRL) for midomafetamine capsules (MDMA) in combination with assisted therapy for adults living with posttraumatic stress disorder (PTSD).1

Upon completion of its review, the FDA stated that it could not approve the treatment based on the data submitted and suggested Lykos Therapeutics conduct an additional phase 3 study to expand on the efficacy and safety profile.

Lykos Therapeutics is planning to meet with the FDA to request "reconsideration of the decision and to further discuss the agency's recommendations for a resubmission seeking regulatory approval for midomafetamine capsules," according to the statement.

“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 stated. "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."

Data from a pair of phase 3 studies submitted by Lykos demonstrated MDMA-AT significantly reduced PTSD symptoms among participants who received the treatment compared with those in the placebo group. The primary outcome was measured by a reduction in Clinician-Administered PTSD Scale for DSM-5 total severity score from baseline to 18 weeks.

Just last week Lykos announced new initiatives and measures for additional oversight for the treatment of adults with PTSD using MDMA-AT.2

PTSD continues to be a significant public health challenge. About 6% of people in the US (8% of women, 4% of men) will have PTSD at some point in their lifetime, according to estimates from the National Center for PTSD.3 However, the consequence of PTSD translates into crisis among the veteran population. While rates of veteran suicide may underestimate the reality, it has been reported that 17 to 44 veterans take their lives each day.4

In a letter to President Joe Biden, more than 60 bipartisan lawmakers from the House and Senate, led by Congress member Jack Bergman, US Representative of Michigan’s First District, addressed the suicide epidemic that’s been affecting veterans for decades. “PTSD and suicide have been exponentially more lethal for those who served in uniform than combat,” the members of Congress wrote.

Selective serotonin reuptake inhibitors (SSRIs) sertraline (Zoloft) and paroxetine (Paxil) have been the only FDA-approved treatment options for PTSD for over 20 years. While SSRIs exhibited superiority compared with placebo in previous research, the effect size paled in comparison to the current MDMA-AT data.5

“With MDMA-assisted therapy, we have an intervention that is roughly 4 times as potent as any existing medication treatment option for PTSD,” MAPP1/2 study investigator Scott Shannon, MD, CEO of the Board of Psychedelic Medicine and Therapies, and founder of Wholeness Center, explained to AJMC.

Related: FDA Committee, Concerned about Bias, Votes No on Psychedelic in PTSD

Many voices have joined the discussion around the psychedelic therapy, which came to a summit at the FDA Psychopharmacologic Advisory Committee (PDAC) public hearing session. In early June, the committee voted 2 to 9 against supporting the effectiveness of MDMA-AT, and 1 to 10 to reject that the benefits of the treatment with the FDA’s proposed risk evaluation and mitigation strategy (REMS) outweigh its risks for the treatment of patients with PTSD.6

Among the data submitted to the FDA in the February 2024 new drug application (NDA) that was granted priority review designation, the agency examined the findings from the pivotal phase 3 clinical trials — MAPP1 and MAPP2.1Both studies evaluated the efficacy and safety of MDMA-AT in patients with PTSD.

“I'm deeply disturbed by the FDA’s unwillingness to look at the data carefully and to have people who are equipped to assess the science make this decision and recommendation,” Shannon said. “I would urge the FDA to create a new division of psychedelic medicine so that we don't lose out on this important avenue of research which has the potential to transform mental health care at a time when we’re deeply mired in crisis and ineffective treatments.”

References

1. Lykos Therapeutics announces complete response letter for midomafetamine capsules for PTSD. News Release. Lykos Therapeutics. August 9, 2024. Accessed August 9, 2024. https://news.lykospbc.com/2024-08-09-Lykos-Therapeutics-Announces-Complete-Response-Letter-for-Midomafetamine-Capsules-for-PTSD

2. Lykos Therapeutics announces new initiatives and measures for additional oversight for midomafetamine-assisted therapy, if FDA approved. News Release. Lykos Therapeutics. August 1, 2024. Accessed August 8, 2024. https://www.prnewswire.com/news-releases/lykos-therapeutics-announces-new-initiatives-and-measures-for-additional-oversight-for-midomafetamine-assisted-therapy-if-fda-approved-302211749.html

3. PTSD: National Center for PTSD. U.S. Department of Veterans Affairs. Updated February 3, 2023. Accessed August 8, 2024. https://www.ptsd.va.gov/understand/common/common_adults.asp

4. Grossi G. Bipartisan letter to President Biden highlights promise of MDMA therapy for PTSD. AJMC. August 7, 2024. Accessed August 8, 2024. https://www.ajmc.com/view/bipartisan-letter-to-president-biden-highlights-promise-of-mdma-therapy-for-ptsd

5. Hoskins MD, Bridges J, Sinnerton R, et al. Pharmacological therapy for post-traumatic stress disorder: a systematic review and meta-analysis of monotherapy, augmentation and head-to-head approaches. Eur J Psychotraumatol. 2021;12(1):1802920. Published 2021 Jan 26. doi:10.1080/20008198.2020.1802920

6. Kunzmann K. FDA Psychopharmacologic Advisory Committee votes against supporting effectiveness of MDMA for PTSD. HCPLive. June 4, 2024. Accessed August 8, 2024. https://www.hcplive.com/view/live-updates-fda-psychopharmacologic-advisory-committee-meeting-mdma-ptsd