In a move certain to have a wider impact on the development of psychedelic-assisted therapies, the MAPS Public Benefit Corporation announced Tuesday that it has filed an application to the FDA for MDMA-assisted therapy for PTSD. This is the first submission of a new drug application for any psychedelic-assisted therapy.
PTSD affects approximately 13 million Americans each year, but available treatments are only modestly effective. In 2014, the MAPS nonprofit organization created the for-profit MAPS Public Benefit Corporation to continue research and education around the development of investigational MDMA-assisted therapy.
According to the MAPS Public Benefit Corporation, the NDA represents more than 30 years of clinical research into MDMA-assisted therapy for PTSD and findings from numerous studies including two randomized, double-blind, placebo-controlled Phase 3 trials, MAPP1 and MAPP2.
Both Phase 3 trials met their primary and secondary endpoints and were published in Nature Medicine. They evaluated the efficacy and safety of MDMA-assisted therapy versus placebo with therapy in participants diagnosed with moderate, or moderate and severe PTSD.
Psychedelics Assisted by Therapy
In this proposed treatment, MDMA (midomafetamine capsules) is used in combination with psychotherapy, talk therapy and other psychological support services provided by a healthcare provider. MDMA-assisted therapy has been studied as an acute therapy made up of three treatment cycles over a 12-week period. Each treatment cycle in the research was made up of one medication session and three sessions of integration. Prior to the 12-weeks of treatment, research subjects also engaged in three preparatory sessions.
“The filing of our NDA is the culmination of more than 30 years of clinical research, advocacy, collaboration and dedication to bring a potential new option to adults living with PTSD, a patient group that has experienced little innovation in decades,” said Amy Emerson, chief executive officer, MAPS PBC. “If approved, MDMA-assisted therapy would be the first psychedelic-assisted therapy, which we hope will drive additional investment into new research in mental health.”
Across the psychedelics ecosystem, many consider the NDA filing a significant milestone.
“The importance to the field of psychiatry of the feat by MAPS PBC of meeting FDA requirements for replicate studies of a combination of talk therapy and MDMA cannot be overstated,” says Jonathan Sporn, CEO of Gilgamesh, a clinical-stage biotech company that develops psychedelic medicines. “This combination of talk therapy and a rapid acting drug therapy is a paradigm shift for psychiatry that will push other drug development programs to consider the importance of this combined therapeutic approach.”
The FDA’s approval of MDMA would affect a broad class of drugs, says Sporn, including “classic psychedelics, and atypical psychedelics (eg, ibogaine)” that show promise in clinical trials, when used alongside therapy, for treating mental health conditions “such as depression, anxiety disorders, substance use disorders, and PTSD. More research is required and hopefully approval of MDMA will unlock additional funding by NIH to understand the science.”
The MPBC filing is expected to be followed in the coming months by NDAs from two other psychedelic companies, COMPASS Pathways and Awakn Life Sciences. Both have psychedelic compounds in Phase 3 clinical trials. Lindsay Hoover, managing partner of the psychedelic venture capital firm JLS Fund, noted that “investors will be closely monitoring the FDA’s response to the NDAs filed by these companies.”
Since the FDA granted MDMA Breakthrough Therapy designation in 2017, MAPS PBC has requested that the FDA now grant Priority Review of the NDA. The FDA has 60 days to determine whether the NDA will be accepted for review and whether it will be a priority or a standard review, which are completed within six or ten months respectively.
“An FDA approval in as early as six months would be a significant indication to the market that not only have psychedelics crossed the rubicon of regulatory acceptance, but the door is open for other psychedelic medicines that prove their effectiveness in clinical trials to reach millions of patients worldwide,” says Hoover.
But timing is not the most important signal to watch for, Hoover adds. “Whether priority approval is granted or not, the NDA approval of a psychedelic therapeutic by the FDA will send a powerful market signal about the potential impact of significantly improved mental health treatments in pharma and the prospective value of companies in this sector overall.”
If approved by the FDA, the U.S. Drug Enforcement Administration will be required to reschedule MDMA making it available for prescription medical use. But that does not mean MDMA will be available outside of regulated channels, explains attorney Joshua Kappel, founding partner at the drug policy law firm Vicente LLP.
“MDMA being approved as a prescription drug would only allow those who hold a lawful registration or prescription to possess MDMA, and only under the restrictions of that prescription or registration. One of those restrictions is that the MDMA must be produced by a licensed pharmaceutical manufacturer,” says Kappel.
The recreational use of MDMA will not be legal, he adds. “This includes personal possession of common street drugs that might contain MDMA.”
MDMA has been a Schedule 1 drug under the Controlled Substances Act since 1985 which has prevented it from being used for medical purposes. Placebo-controlled studies examining the use of MDMA-assisted therapy for treatment-resistant PTSD began in the 2000’s.
The Road Ahead
While the NDA filing brings MAPS closer to the goal it has pursued for over three decades, it still has further to go.
Ryan Zurrer, managing partner of Vine Ventures, a VC fund that developed an innovative investment vehicle for MAPS PBC, stresses the importance of “maintaining focus on the larger goal of FDA approval and the opportunity to deliver care to patients in America and globally.”
Zurrer says he is proud of the role Vine has played to help “MAPS get to this point.” He notes, however, that “there is a lot of work to still do. Today is not a day for champagne, it’s a day for coffee and getting back to work.”