The U.S. Food and Drug Administration has declined to approve the psychedelic drug MDMA as a therapy for Post Traumatic Stress Disorder, vanquishing any prospect that the controversial mind-altering drug, also known as Ecstasy or Molly, will be a forthcoming tool of modern medicine.
San Jose-based drugmaker Lykos Therapeutics said the FDA notified the company that the drug “could not be approved based on data submitted to date,” and requested an additional late-stage study, which could take several years and millions of dollars to conduct. The drugmaker said it plans to ask the agency to reconsider.
In rebuffing the application, the FDA sent a strong signal that it was exercising considerable caution in assessing the use of psychedelics for therapeutic uses. More applications from other companies are expected to be reviewed by the FDA in coming years.
Two Phase 3 trials suggested the treatment was effective. Last June, an FDA scientific advisory committee wrote that patients who received MDMA and talk therapy showed “rapid, clinically meaningful, durable improvements in their PTSD symptoms.”
But the committee also called the research “challenging to interpret” because it’s difficult to know whether improvement came from the drug or talk therapy. Additionally, it raised several safety concerns, including MDMA’s heart risks and potential for abuse.
On Friday, an FDA spokesperson said that the drug application had “significant limitations” that “prevent the agency from concluding that the drug is safe and effective for the proposed indication.” The agency requested that Lykos conduct an additional Phase 3 trial.
Lykos said it will request a meeting with the FDA to ask for reconsideration of the decision and to further discuss the agency’s recommendations for a resubmission of its application.
Lykos and its parent organization Multidisciplinary Association for Psychedelic Studies (MAPS) have worked for decades to earn approval. The effort had its start 38 years ago ago in a converted three-bedroom house on Santa Cruz’s Mission Street, rented by MAPS founder Rick Doblin..
Research for the prescription capsule was conducted at UC San Francisco and funded by venture capital — with patents, and profits, on the horizon.
If approved, MDMA-assisted therapy would have been the first novel treatment for PTSD, which occurs after exposure to a violent or traumatic event. Antidepressants are now the only approved drugs for PTSD. But fewer than 60% of patients respond to this approach, and only 20% to 30% of patients are cured, according to a 2009 article in the journal Progress in Neuro-Psychopharmacology and Biological Psychiatry.
“MDMA allows you to access these really deep traumatic memories in a way that is not anxiety-provoking,” Jennifer Mitchell, a UCSF neuroscientist who led a study being presented to the FDA, told the Mercury News in 2022.
Clinical trial participant and retired Army Sgt. Jonathan Lubecky, 46, who lives in Washington, D.C., said MDMA tamed his symptoms. He suffered severe PTSD after a year in Iraq, regularly waking up from nightmares in a cold sweat.
Boris Heifets, a neuroscience researcher at Stanford University who studies psychedelics, told the online medical news site STAT he was surprised at the FDA’s decision, adding he’d expected the agency would approve the drug with a requirement for post-approval studies.
The drug has long lingered in the shadows of counterculture. It is currently classified by the Drug Enforcement Agency as a Schedule 1 drug, like heroin, with “no currently accepted medical use and a high potential for abuse.”
MDMA research got the nod from the FDA in 2017 when it was granted “breakthrough therapy” status, which allowed experiments to be fast-tracked.
In highly regulated studies, it showed promise in reducing PTSD symptoms, when combined with psychotherapy with a trained professional to talk about thoughts, feelings, and behaviors. It’s not a classic hallucinogen like LSD; instead, it triggers feelings of intimacy, connection, and euphoria.
The federal government cautions that use can cause confusion, depression, anxiety, sleeplessness and paranoia, as well as physical symptoms such as muscle tension, involuntary teeth clenching, nausea, sweating, or chills. People who have circulatory problems or heart disease face particular risks because MDMA can increase heart rate and blood pressure.
In the UCSF trial funded by Lykos, patients received MDMA as part of an intensive, four-month course of talk therapy lasting more than a dozen sessions, of which three involved taking the drug. By the end of one study, 86% of people in the MDMA group improved and 71% no longer met the criteria for a PTSD diagnosis. Of those who took the placebo, 69% improved, and 48% no longer qualified for a PTSD diagnosis.
But the FDA’s staff analysis said there were flaws in the study because it was not truly “blinded.” Participants and therapists were able to figure out who got MDMA versus the placebo.
If the product had been approved, Lykos would have the sole rights to commercialize it for five years. Under the leadership of CEO Amy Emerson, formerly of pharma giants Novartis and Chiron, the company raised about $150 million and grown to over 120 employees.
“The FDA request for another study is deeply disappointing,” Emerson said Friday in a statement. “Our heart breaks for the millions of military veterans, first responders, victims of sexual and domestic abuse and countless others suffering from PTSD who may now face more years without access to new treatment options.”
Additional psychedelics for therapeutic uses are expected to be reviewed by the FDA in coming years.
Originally Published: