One pharmaceutical company’s plans to develop a treatment for Post-Traumatic Stress Disorder using midomafetamine (also known as MDMA, as well as ecstasy or Molly when used as a street drug) have stalled.
This Tuesday the U.S. Food & Drug Administration’s Psychopharmacologic Drugs Advisory Committee voted not to recommend a proposed therapy from California-based Lykos Therapeutics. They asked for more information about therapy services that would be part of the treatment, more lab data and more.
Lykos was seeking approval for the use of midomafetamine capsules in combination with psychological intervention. According to a presentation made at the committee meeting, there was a “statistically significant and clinically meaningful improvement in PTSD symptoms and functional impairment,” across three trials.
Currently, MDMA is considered a schedule I drug by the U.S. Drug Enforcement Agency. That means it has no “currently accepted medical use and a high potential for abuse.”
“Ecstasy/MDMA acts as both a stimulant and hallucinogen, producing an energizing effect, distortions in time and perception, and enhanced enjoyment of tactile experiences,” and it promotes euphoria, feelings of closeness, empathy, and sexuality, per the DEA. A laboratory created-substance originating in the U.S., it is known for its use at parties and raves and is often pressed into pills with a variety of logos and colors.
In this application, it has been linked with side effects including inhibiting the body’s ability to regulate temperature. This complication can also lead to liver, kidney, or cardiovascular system failure, swelling of the brain, and even death.
Documents from Lykos provided by the FDA noted that PTSD affects an estimated 13 million Americans annually, with women and disadvantaged or marginalized groups more likely to be affected. PTSD can substantially impact day-to-day functioning for those who suffer from it.
“On average, patients experience PTSD symptoms for more than 6 years and approximately 48% of patients remain untreated,” said Lykos. “Evidence-based, individual trauma-focused psychotherapy is the recommended first line treatment over available pharmacologic interventions.”
Those pharmacologic interventions include two FDA-approved SSRIs for treatment of PTSD, sertraline as well as another SSRI and a SNRI used off-label to treat PTSD. Patients are required to take these medications daily for at least 12 weeks and long-term consistent use is generally needed to see results.
According to the Lykos presentation, there have been no FDA-approved treatments for PTSD in 20 years. Lykos also said that the MDMA treatment “facilitates memory recollection, extends tolerance for revisiting distressing thoughts or experiences,” and “increases self-awareness leading to introspection and personal reflection,” along with being well-tolerated by patients.
However, multiple issues with the trails were addressed during Tuesday’s meeting.
One is related to an ethics complaint that was reported in 2018 by a trial participant.
“The complaint specifically identified the unethical conduct as occurring after the active treatment sessions had concluded in 2015,” said a statement from the Multidisciplinary Association for Psychedelic Studies (MAPS) regarding treatment provided by former sub-investigator Donna Dryer and her partner Richard Yensen.
Per MAPS, “Yensen engaged in a sexual relationship with the participant,” which constitutes unethical conduct. Following the revelation, Yensen and Dryer were barred from all MAPS-related activities and from becoming providers of MAPS-affiliated MDMA-assisted therapy if the treatment is approved.
In 2022, CBC reported on videos of Meaghan Buisson, a hiking guide based on Vancouver Island who was a patient of the trial, being pinned down by Yensen “as she moans in obvious anguish.”
“This is horrific. This happened in a Health Canada-approved clinical safety trial,” she said, according to the outlet. “For that to happen in this environment, under far more scrutiny than the substance will ever again be under, is extremely troubling.”
In March, the Institute for Clinical and Economic Review (ICER) – an independent organization – issued a report about two Phase III clinical trials, MAPP1 and MAPP2 that evaluated the short-term efficacy and safety of the Lykos MDMA treatment. ICER said 194 adults were enrolled in the trials.
“If these results are reflective of the expected outcomes if MDMA-AP is administered broadly to people with PTSD, it would be an important addition to treatment options for PTSD, an often severe and disabling condition,” said the report. “However, we have substantial concerns about the validity of the results.”
These were related to the fact that the trials were “unblinded” along with comments from experts about strong prior beliefs of people involved in the trials.
“Concerns have been raised by some that therapists encouraged favorable reports by patients and discouraged negative reports by patients including discouraging reports of substantial harms, potentially biasing the recording of benefits and harms,” ICER explained.
Lykos said in a Tuesday press release that the FDA committee voted no (2 to 9) on the question of whether the available data show that midomafetamine is effective in patients with PTSD and no (1 yes to 10) on the question of whether the benefits of midomafetamine with FDA’s proposed risk evaluation and mitigation strategy (REMS) outweigh its risks for the treatment of patients with PTSD. It also said the FDA is not bound by PDAC's guidance but takes its advice into consideration.
“We are disappointed in today’s vote given the urgent unmet need in PTSD and appreciate that the committee faced a challenging and atypical assignment, which was to evaluate a therapeutic approach that combines drug therapy (MDMA) and psychological intervention,” said Amy Emerson, CEO of Lykos Therapeutics. “We remain committed to working with the FDA to address outstanding questions so that we may find a path forward to ensure the responsible and careful introduction of MDMA-assisted therapy into the healthcare system, if approved.”
She said the company plans to continue its work to develop this therapeutic option for people with PTSD using MDMA.
This February, the FDA accepted the company’s new drug application and granted the application Priority Review. An FDA approval decision is expected by the Prescription Drug User Fee Act target action date of Aug. 11.