FDA Advisory Committee Rejects Lykos’ MDMA Therapy For PTSD

In disappointing news for psychedelic medicine advocates, an FDA advisory panel has rejected the approval of MDMA as a treatment for post-traumatic stress disorder (PTSD).

Yesterday was a big day for the psychedelic medicine space, one of the final steps before the FDA makes its final decision on whether or not to approve MDMA. The FDA’s Psychopharmacologic Drugs Advisory Committee (PDAC) met to review Lykos Therapeutics’ New Drug Application (NDA). Lykos, formerly MAPS PBC, has successfully completed Phase 2 and Phase 3 trials with promising results and is moving forward with a New Drug Application.

The advisory panel, however, delivered a rebuke of Lykos’ proposed MDMA-assisted treatment. The Psychopharmacologic Drugs Advisory Committee rejected the approval of MDMA as a treatment for PTSD, saying that according to the FDA’s risk evaluation and mitigation strategy (REMS), the benefits do not outweigh its risks for the treatment of PTSD.

The board voted 10-1 against the treatment. 

The panel’s vote was split into two parts: one on the treatment’s efficacy and one on its safety. The committee ultimately decided against recommending MDMA for PTSD treatment, citing flawed trials conducted by Lykos Pharmaceuticals. The committee’s concerns centered on data inconsistencies, poor study design, and allegations of misconduct during the trials.

Dr. Walter Dunn from UCLA was the only panel member to vote “yes” on safety and one of the two members who voted “yes” on efficacy. Dunn remarked that in medicine, potential benefits often come with potential harms, acknowledging the drug’s potential and emphasizing the urgent need for new PTSD treatments.

The panel’s decision was informed by two Phase 3 clinical trials involving nearly 200 patients with moderate to severe PTSD. These trials indicated that MDMA, combined with therapy, reduced PTSD symptoms more effectively than a placebo. In the most recent trial, published last September, 86% of participants who received MDMA and therapy showed reduced symptoms after 18 weeks, compared to 71% in the placebo group.

Despite these positive findings, the FDA scientists raised concerns about the trials’ methodology. They pointed out that the trials could not be truly double-blinded, as participants often guessed whether they had received MDMA due to its profound effects. This issue, known as “functional unblinding,” could potentially skew the results.

Additionally, panel members were troubled by allegations of sexual misconduct by providers during an earlier trial. This issue, along with other potential risks to patients, significantly influenced the panel’s decision.

Some psychedelic medicine experts, like Dr. Matthew Johnson from Johns Hopkins, believed the panel’s concerns were overblown. 

 

The panel’s vote is only a recommendation, and the final decision will be made by the FDA in August. 

Historically, the FDA has generally followed the advisory committee’s recommendations, but a closer look shows that all hope is not lost. A study published in JAMA looked at how the FDA handled committee recommendations from 2010 to 2021. According to the study: 

“The authors found high agency alignment with committee advice when the committee recommended approval: 97% of drug applications were approved when the committee advised approval. However, they also found that when the committee did not recommend approval, the FDA was only in agreement 67% of the time.”

Put simply, the FDA still approved about one-third of applications even after the committee recommended not to. 

Of note: The FDA has already given this MDMA therapy support through its Breakthrough Designation Status, as well as approving the results during the various Phase 2 and Phase 3 trials. So the hope for Lykos, psychedelic medicine advocates, and PTSD patients looking for alternative treatments, is that this MDMA trial will beat the odds and still receive FDA approval. 

Stay tuned to Microdose for more.