Major Milestone for Psychedelic-Assisted Therapy

Lykos Therapeutics Submits New Drug Application to the FDA for MDMA-Assisted Therapy for PTSD

On Dec. 12, 2023, the Multidisciplinary Association for Psychedelic Studies Public Benefit Corporation (MAPS PBC) announced their submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for MDMA (midomafetamine) in combination with psychotherapy for the treatment of post-traumatic stress disorder (PTSD). (Press Release, Lykos Therapeutics, “MAPS PBC Announces Submission of New Drug Application to the FDA for MDMA-Assisted Therapy for PTSD” (Dec. 12, 2023). This marks the first NDA submission for any psychedelic-assisted therapy and is a major milestone for the medicinal psychedelics industry.

Subsequently, on Jan. 5, 2024, MAPS PBC announced a name change/rebranding to Lykos Therapeutics, as well as the successful close of an oversubscribed Series A financing of over $100 million, which will help fund the regulatory approval and pre-launch steps for MDMA-assisted therapy for PTSD. (Press Release, Lykos Therapeutics, “MAPS Welcomes New Investors, Name Change for MAPS Public Benefit Corporation” (Jan. 5, 2024).

MDMA, often grouped in the category of psychedelics, is a synthetic psychoactive compound classified as an entactogen, meaning it induces emotional states such as openness and oneness. Mental health professionals were already using MDMA in combination with psychotherapy to treat patients in the 1970s, but in 1985, the U.S. Drug Enforcement Administration (DEA) categorized MDMA (also known as ecstasy) as a Schedule I drug under the Controlled Substances Act precluding its medical use.

In the 2000s, renewed interest in this compound led to a marked increase in investigational placebo-controlled studies of MDMA-assisted therapy for PTSD. In 2017, the FDA granted MDMA-assisted therapy for PTSD “breakthrough therapy” status—a designation designed to speed up the development and review of medications for serious conditions where preliminary clinical evidence has suggested the medication may show substantial improvement over available therapy on a clinically significant endpoint(s). (Press Release, MAPS, “FDA Grants Breakthrough Therapy Designation for MDMA-Assisted Therapy for PTSD, Agrees on Special Protocol Assessment for Phase 3 Trials” (Aug. 26, 2017).

MAPS PBC (now known as Lykos Therapeutics) conducted six Phase 2 and two Phase 3 studies evaluating the use of MDMA-assisted therapy for PTSD. The two pivotal Phase 3 studies (MAPP1 and MAPP2) were randomized, double-blind, placebo-controlled trials in 90 and 104 subjects, respectively, with PTSD. (Jennifer M. Mitchell et al., “MDMA-Assisted Therapy for Severe PTSD: a Randomized, Double-Blind, Placebo-Controlled Phase 3 Study”, 27 Nature Med. 1025, 1025-33 (2021) and Jennifer M. Mitchell et al., “MDMA-Assisted Therapy for Moderate to Severe PTSD: a Randomized, Placebo-Controlled Phase 3 Trial”, 29 Nature Med. 2473, 2473-80 (2023).) Therapy involved three preparatory sessions followed by three treatment cycles over a three-month period with each treatment cycle including one medication session (where the patient self-administered MDMA under the supervision of a healthcare provider(s) who also delivered psychotherapy) and three integration sessions.

Both studies met the primary endpoint measuring PTSD symptomology by the change from baseline to 18 weeks in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and a secondary endpoint of improvement in functional impairment associated with PTSD as assessed by the change from baseline to 18 weeks in the Sheehan Disability Scale (SDS). In both studies, no serious adverse events were reported in the group which received MDMA-assisted therapy.

In a press release, Amy Emerson, CEO of Lykos Therapeutics, stated: “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.” (Lykos Therapeutics, Dec. 12, 2023, supra.)

Lykos Therapeutics asked the FDA for priority review of their NDA. The FDA will decide within 60 days if the NDA will be accepted for review and if it will be a priority or standard review (six months or 10 months, respectively).

An approval by the FDA of MDMA-assisted therapy for PTSD would also require the DEA to change the Schedule I classification of Lykos Therapeutics’ formulation of MDMA so that it can be used as a prescription medication. This is because Schedule I is reserved for drugs with a high abuse potential but no accepted medical use. Drugs with abuse potential that do have accepted medical use—or, in other words, are FDA-approved products—are placed into Schedule II, III, IV or V depending on their relative abuse potential and degree to which they induce dependence.

The drug scheduling process includes multiple steps and federal agencies. The Controlled Substance Staff within the FDA performs an eight-factor analysis (8FA) of the abuse-related data submitted in the NDA and, together with input from the National Institute on Drug Abuse (NIDA) staff, makes scheduling recommendations. (U.S. Department of Health and Human Services, FDA and Center for Drug Evaluation and Research, “Assessment of Abuse Potential of Drugs: Guidance for Industry”, FDA (Jan. 2017).

The Department of Health and Human Services (HHS) considers the 8FA and recommendations and then transmits the 8FA and scheduling recommendations to the DEA, which makes the final rescheduling decision.