FDA rejects MDMA-assisted therapy for PTSD

The FDA has refused to approve a mycobacterial drug called methadone (MDMA) capsule for post-traumatic stress disorder (PTSD), calling for separate trials to evaluate the drug's effectiveness and safety, its developer said. Lycos Therapeutics Announces on friday.

Lycos said the FDA has determined that “based on the data submitted to date, this investigational psychedelic agent is not appropriable” and has requested further Phase 3 trials. The company plans to ask the FDA for reconsideration.

Although this decision was eagerly anticipated, FDA Advisory Committee In June, by a vote of 9 to 2, Psychopharmacology Drug Advisory Committee The committee said the available data failed to show that MDMA is effective in treating PTSD patients. The committee also voted 10-1 that the risks outweigh the benefits, even with the proposed Risk Evaluation and Mitigation Strategy (REMS).

Ahead of the June meeting, FDA reviewers Concerns raised Cardiac safety concerns included significant increases in blood pressure and pulse rate, which could lead to cardiovascular events, and there were additional safety concerns, including long-term disability and vulnerability, and potential for abuse.

Institute for Clinical and Economic Review (ICER) report from March Published trial data were evaluated The response to MDMA-assisted therapy is “inadequate.”

But pressure has been building in recent days for the FDA to approve the product.

Earlier this week, more than 60 bipartisan lawmakers I wrote a letter The Biden administration urged approval, citing a “critical need for new and better treatment options like MDMA-assisted therapy” for veterans and military personnel. The condition affects about 5% of the U.S. population each year, according to the VA National Center for PTSD. More prevalent Among the military.

“We are disappointed that the FDA has requested new studies,” said Lycos CEO Amy Emerson. “It is heartbreaking that millions of veterans, first responders, victims of sexual abuse and domestic violence, and countless others suffering from PTSD may face years of not having access to new treatment options.”

The FDA said Friday that the MDMA application has “significant limitations” that “prevent the agency from concluding that the drug is safe and effective for its proposed indication.” The agency said it will continue to encourage “innovation in psychedelic treatments and other therapies to address these medical needs.”

If approved, MDMA, also known as ecstasy and Molly, would have been the first federally approved illegal hallucinogen.

This treatment would also have been the first PTSD treatment in over 20 years. The selective serotonin reuptake inhibitors (SSRIs) sertraline and paroxetine are currently the only drugs FDA-approved to treat PTSD. Other evidence supports the use of the SSRI fluoxetine and the selective serotonin-norepinephrine reuptake inhibitor venlafaxine. However, Usually less than 20% to 30% Proportion of patients achieving complete remission with SSRIs.

Both Phase 3 clinical trials conducted by Lykos achieved their primary endpoint of significant improvement in DSM-5 Clinician Administered PTSD Scale (CAPS-5) scores. Participants received three MDMA dosing sessions and additional psychological support sessions before and after dosing.

in Map 1The group receiving MDMA and psychotherapy experienced an average drop of 24.4 points in their CAPS-5 scores, compared with an average drop of 13.9 points in the group receiving psychotherapy only. By the end of the third session, 30% of the MDMA group had achieved PTSD remission, 60% had achieved dediagnosis, and 80% of the group were deemed to have responded to treatment. Meanwhile, in the group receiving only psychotherapy, less than 5% achieved PTSD remission and only half responded to treatment.

Map 2 Similar results were reported, with MDMA-treated patients experiencing an average reduction in CAPS-5 scores of 23.7 points compared with a 14.8 point reduction in the group receiving psychotherapy alone. In both studies, patients taking MDMA also met pre-specified secondary endpoints.

The FDA's decision to again require Phase 3 clinical trials “is a major setback for the field,” Dr. Jennifer Mitchell, a MAPP researcher at the University of California, San Francisco, said in the Lycos announcement.

MDMA is the first in a series of psychedelic drugs expected to be reviewed by the FDA in the coming years amid renewed interest in its therapeutic potential.

The idea of ​​using psychedelics to enhance psychotherapy is not new: In California, several therapists used MDMA to facilitate couples' therapy sessions in the 1970s and 1980s, when it was still legal.

Lycos is essentially a corporate spinoff of the nation’s leading psychedelic drug advocacy group, the Multidisciplinary Association for Psychedelic Drug Studies (MAPS), which was founded in 1986 to fight the federal government’s decision to classify MDMA in the same highly regulated drug category as heroin, LSD, and other illegal hallucinogens.

MAPS's MDMA research began more than a decade ago. Since then, dozens of small, start-up pharmaceutical companies have entered the field, studying other substances like psilocybin and LSD for conditions like depression, addiction and anxiety. These studies are generally larger and more rigorous than the MDMA studies submitted to the FDA.

Two drug development companies, Compass Pathways and Usona Research, are conducting late-stage studies of the effects of psilocybin, the active ingredient in magic mushrooms, on severe depression.

The Enterprise and investigative reporter Michael DePauw Wilson and The Associated Press contributed to this report.