Preparing for MDMA-Assisted Therapy

MAPS submits New Drug Application to FDA

On Tuesday, the Multidisciplinary Association for Psychedelic Studies (MAPS) issued a monumental (and heavily acronym-laden) announcement that it had submitted a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for MDMA-Assisted Therapy (MDMA-AT) for the treatment of Post-Traumatic Stress Disorder (PTSD).

From the press release:

“MAPS Public Benefit Corporation (“MAPS PBC”), a clinical-stage company dedicated to changing the way mental health conditions are treated, announced the submission of a new drug application (“NDA”) to the U.S. Food and Drug Administration (“FDA”) for MDMA (midomafetamine capsules) used in combination with psychological intervention, which includes psychotherapy, or talk therapy, and other supportive services provided by a qualified healthcare provider.”

This marks the final leg of a nearly 40-year journey that Rick Doblin and MAPS have been on since the founding of the non-profit in 1986 to salvage MDMA-AT as a treatment option for a devastating condition.

Back in September, when MAPS published peer-reviewed results of its second and final Phase III trial, we noted that the next step would be NDA submission and the steps and timeline involved.

From MAPS Reaches The Last Mile: Part I:

The NDA is the formal last step taken by a drug sponsor to request that the FDA approve a new drug for sale and marketing in the United States.

The purpose is to demonstrate to the FDA that the drug is safe and effective for its intended use, manufactured correctly, and appropriately labeled and packaged. It will include information about the chemistry and manufacturing processes, results from animal and preclinical toxicology studies, data about how the drug is absorbed, metabolized, and excreted, data from Phase I-III clinical trials, updated safety reports, and plans for pediatric trials, among other things.

A standard review process requires the FDA to come to a decision within ten months of the NDA submission. If an NDA is awarded Priority Review, it means the FDA will make a decision within six months.

Two distinctions can help the review timeline and increase the likelihood of approval.

In 2017, the FDA awarded Breakthrough Therapy Designation to the MDMA-AT program. Breakthrough status allows “All Fast Track” designation features and “intensive guidance on an efficient drug development program, beginning as early as Phase 1.”

MAPS also has a Special Protocol Assessment (SPA) in place with the FDA, which allows drug sponsors to agree on the study design, size, endpoints, and statistical measurements with the FDA. 

Although achieving the apriori benchmarks set by a SPA does not guarantee approval, meeting these benchmarks is a very good sign.

If all goes as planned, we could see FDA approval by the end of 2024 and a commercial rollout of MDMA-AT in early 2025.

Now, with the formal submission of the NDA, I thought it would be useful to sketch out the key decisions that are forthcoming that will affect healthcare providers’ ability to plan for providing MDMA-AT.

Deciding whether a new drug is safe and effective for commercial marketing is ostensibly a cut-and-dry process. However, there are a few unique features of the MDMA-AT decision that healthcare providers (doctors, therapists, etc.) should be aware of when considering the possibility of using MDMA-assisted therapy in their clinical practices.

Drug Labeling 

The drug label that is included on the package insert of an FDA-approved treatment is meant to advise healthcare providers on which diagnoses the drug is approved for, as well as dosing and, in the case of MDMA-AT, instructions on the delivery of concomitant psychotherapy (see below). 

It also has implications for reimbursement, as health insurers usually only pay for treatments for patients based on the indication on the drug label. 

The approved indication for MDMA-AT will presumably be PTSD or ‘severe PTSD’. 

Of course, when a new drug emerges, there are often several other indications or use cases that are not indicated on the drug label.

A high-profile example of this is Semaglutide (aka Ozempic), a GLP-1 agonist originally approved for the treatment of Type-II Diabetes but which found rapid adoption and commercial success in off-label use as a weight loss drug.

I have to imagine the demand for MDMA-AT outside of the relatively narrow indication of PTSD (an estimated 13 million Americans) will be off the charts, and off-label use cases will include everything from couples therapy to depression, anxiety, and other common mental health conditions as well as people who are simply ‘psychedelic curious’ but only trust a licensed product.

Risk Evaluation and Mitigation Strategies

MDMA-AT, like Spravato, will be required to have a Risk Evaluation and Mitigation Strategy (REMS), a protocol required by the FDA, which, as the name suggests, is meant to mitigate risks such as addiction.

The specific procedures for a REMS are unique to each new drug and decided through negotiations between the drug developer and the FDA. 

Some conceivable REMS for MDMA-AT may be the requirement that patients remain on site for a certain period of time after the effects have worn off or that they are monitored by healthcare providers that have a certain level of training, like a registered nurse (RN) or physician’s assistant (PA).

The REMS may also include certain requirements of the facility where MDMA-AT is administered, such as high-security drug storage or onsite pharmacy (although this seems very unlikely), which will make delivering this treatment difficult for smaller practices that do not have access to such amenities.

Practice of Psychotherapy

Third, how the FDA will address the matter of psychotherapy, which was a central component of the clinical trials, may be the unknown with the largest impact. 

While the FDA cannot dictate the practice of medicine, it is responsible for assessing the safety and efficacy of the combined treatment and determining the appropriate use of the drug within the context of the therapy, as this was the context of the clinical trials.

According to the Washington Post, MAPS PBC Amy Emerson “said in a September interview that she expected that, if the treatment is approved, an FDA label would say the treatment ‘needs to be implemented in the way it was studied’ — with a therapy component.”

If psychotherapy is indicated on the drug label, then insurers and payers may end up being the groups that enforce this requirement, but perhaps for only on-label use (?)

Either way, the wrap-around support for patients undergoing MDMA-AT will vary widely, and we should expect to see innovation through group administration, telehealth-enabled support, and demographic-specific offerings (ie, treatment cohorts for veterans).

Rescheduling

Upon FDA approval of a Schedule I substance, the Drug Enforcement Agency (DEA) is tasked with rescheduling it at the federal level, and from there, individual states will need to change their laws.

It is likely MAPS’ MDMA is to be placed into schedule II or III, which has an impact on how tightly controlled the manufacturing, shipment, and storage will need to be—all of which will have downstream costs.

Importantly, any MDMA that does not come from MAPS will still remain in schedule I (most likely).

After all of this, there will be matters of credentialing, medical coding, malpractice insurance, and the like, which we’ll get into over the course of the next year by looking at the work of groups like the American Psychedelic Practitioners Association (APPA), the Board of Psychedelic Medicine and Therapies and Brain Futures.

All told, 2024 will be the year of final preparation for medical access to psychedelic-assisted therapy for the first time.

Let’s Gooooo 🔥🔥🔥🔥🔥