MDMA-Assisted Therapy for PTSD: A Conversation With Amy Emerson, CEO of Lykos Therapeutics

CLINICAL CONVERSATIONS

The US Food and Drug Administration (FDA) Advisory Committee Meeting will meet on June 4, 2024, to review investigational MDMA-assisted therapy for posttraumatic stress disorder (PTSD). In advance of this meeting, we asked Amy Emerson, the CEO of Lykos Therapeutics, a few questions on this treatment and its potential impact on the future of clinical psychiatry.

PT: Can you share your thoughts on the upcoming FDA Advisory Committee Meeting to review investigational MDMA-assisted therapy for PTSD, the potential first new PTSD treatment in 25 years?

Amy Emerson: On June 4th, the FDA’s Psychopharmacologic Drugs Advisory Committee will review results from numerous studies including 2 randomized, double-blind, placebo-controlled phase 3 studies (MAPP1 and MAPP2) evaluating the efficacy and safety of MDMA used in combination with psychological intervention, which includes psychotherapy and other supportive services provided by a qualified health care provider, vs placebo with psychological intervention in participants diagnosed with severe or moderate to severe PTSD, respectively.

In addition to being the first FDA advisory committee meeting to review a potential new PTSD treatment in 25 years,¹ this will be the first MDMA-assisted therapy and psychedelic-assisted therapy to be reviewed by an FDA advisory committee. Since this is a potential first-in-class product, we were expecting there would be an FDA Advisory Committee meeting.

Advisory Committees are quite routine for first in class treatments. Recent examples include exagamglogene autotemcel (exa-cel), a gene therapy for sickle cell disease developed by Vertex Pharmaceuticals and NARCAN (naloxone hydrochloride), a nonprescription nasal spray treatment for suspected opioid overdose developed by Emergent BioSolutions.

This committee meeting is a significant milestone in the field of psychedelic medicine and we look forward to the opportunity to discuss the comprehensive data package of investigational MDMA and how, if approved, it may be used as a prescription treatment in combination with psychological intervention in adults with PTSD.

PT: If approved, how will MDMA change the future treatment of PTSD?

Emerson: PTSD poses a global mental health challenge, can be undiagnosed or misdiagnosed, and affects individuals for years.^2,3 Current treatments for PTSD can be effective for some; however, they can also be associated with low adherence rates and early dropouts due to tolerability issues with reexposure to trauma, tolerability of medication, and/or insufficient response to treatment.^4-7 These challenges underscore the urgent need for new, evidence-based therapies and approaches to address this important public health issue.

With no FDA approved PTSD treatment options in over 20 years,⁸ if approved, this new modality may help to address this significant unmet need, especially as there are more than 13 million Americans who are affected by PTSD each year.⁹

PT: Will Lykos be helping with the integration of MDMA-assisted therapy into clinical practice? Do you have any insight into potential reimbursement issues?

Emerson: We believe payors see the need for new PTSD treatments and are committed to doing our part to support patient access. If investigational MDMA capsules used in combination with psychological intervention is approved by the FDA, we will focus on the integration of psychedelic-assisted therapy into the health care system with a quality-focused launch.

Our plan is to work with sites of care that have:

• Integrated care (prescriber and therapist)
• Infrastructure in place to coordinate care
• Payor coverage

Given the novel nature of this potential intervention, it is important that we consider the reimbursement pathway for a combination treatment. That is why we collaborated with COMPASS Pathways last year to work with the American Medical Association to create CPT III codes, a set of temporary codes assigned to emerging technologies, services, and procedures, to facilitate reimbursement and support access to psychedelic therapies in the United States, if such therapies receive regulatory approval by the FDA. The new CPT III codes are intended to be used for data collection to substantiate sufficient usage, which could lead to them to be converted to permanent CPT I codes with a valuation assigned for widespread coverage and reimbursement.

PT: What do you think clinicians should know about the MAPP1 and MAPP2 studies? What are the most important takeaways?

Emerson:Data from our MAPP2 clinical trial, a multi-site phase 3 study of MDMA-assisted therapy for PTSD, was published in the September issue of Nature Medicine. The MAPP2 study met its primary and secondary endpoints confirming the results seen in the first phase 3 study (MAPP1) that were also published in Nature Medicine.

The treatment regimen studied took about 12 weeks and comprised of 3 treatment cycles. Each treatment cycle consists of 1 medication session and approximately 3 integration sessions. During the medication sessions a patient self-administers MDMA under the supervision of a qualified health care professional who provides psychotherapy and other supportive services. This is followed by a series of integration psychotherapy sessions to process the therapeutic gains. More detailed information about the trial design and results can be found in the publications.

PT: Critics have claimed the study results are biased because it is not possible to truly blind the active treatment. What can you tell readers to make them feel more comfortable with how the studies were conducted and their results?

Emerson: We have worked closely with the FDA through every step of the process including in our trial design. Functional unblinding is a known challenge in many double-blind clinical studies, especially if the drug has prominent psychoactive effects (eg, antipsychotics). To address functional unblinding directly, we designed our trials in collaboration with the FDA through a Special Protocol Assessment in 2017.

As a result, we worked with the Agency to establish various measures to mitigate bias throughout our clinical program including using the clinician-administered PTSD scale administered by independent raters who were blinded to the study design, the treatment, and assessed each participant once postscreening.

PT: In your biography, you state that you and your colleagues at Lykos are “dedicated to changing the way mental health conditions are treated.” Can you elaborate on that?

Emerson:There is an urgent need for more innovation in mental health care. We are exploring and reimagining novel approaches to potentially address unmet needs in the mental health care space, with an initial focus on PTSD.

Trauma-focused psychotherapy is the recommended standard of care for treatment of individuals with PTSD which can be used alone or in combination with medication. Current treatments for PTSD can be effective for some; however, they can also be associated with low adherence rates and early dropouts due to tolerability issues with reexposure to trauma, tolerability of medication, and/or insufficient response to treatment. These challenges underscore the urgent need for new, evidence-based therapies and approaches to address this important public health issue.

With no FDA approved PTSD treatment options in over 20 years, we are focused on developing new, potentially effective approaches for the more than 13 million Americans who are affected by PTSD.

PT: What are the next steps for Lykos?

Emerson:We are focused on preparing for the FDA Advisory Committee meeting, and working with the FDA to determine what will be included in a potential prescription label and Risk Evaluation and Mitigation Strategy program if our investigational MDMA capsules used in combination with psychological intervention is approved by the FDA for adults with PTSD.

If FDA approves, prescription MDMA will be launched with a careful consideration of its potential benefits and risks, in accordance with established medical guidelines, protocols, and quality standards.

Because this is a new approach, we believe that training is critical for qualified health care providers interested in delivering MDMA-assisted therapy. We will be offering a robust training program on how investigational MDMA-assisted therapy was delivered in our phase 3 program to support clinicians in achieving optimal real-world outcomes. Our goal is to scale responsibly to ensure availability of MDMA-assisted therapy to the mental health community more broadly over time.

PT: Thank you!

Ms Emerson is the CEO Of Lykos Therapeutics.

References

1. FDA. Federal Register. 1999;64(165). Accessed April 2024. https://www.govinfo.gov/content/pkg/FR-1999-08-26/html/99-22103.htm

2. Qassem T, Aly-ElGabry D, Alzarouni A, et al. Psychiatric co-morbidities in post-traumatic stress disorder: detailed findings from the adult psychiatric morbidity survey in the English population. Psychiatric Q. 2021;92(1):321-330.

3. Gagnon-Sanschagrin P, Schein J, Urganus A, et al. Identifying individuals with undiagnosed post-traumatic stress disorder in a large United States civilian population – a machine learning approach. BMC Psychiatry. 2022;22(1):630.

4. Berger W, Mendlowicz MV, Marques-Portella C, et al. Pharmacologic alternatives to antidepressants in posttraumatic stress disorder: a systematic review. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(2):169-180.

5. Machado-Vieira R, Baumann J, Wheeler-Castillo C, et al. The timing of antidepressant effects: a comparison of diverse pharmacological and somatic treatments. Pharmaceuticals (Basel). 2010;3(1):19-41.

6. Steenkamp MM, Litz BT, Hoge CW, Marmar CR. Psychotherapy for military-related PTSD: a review of randomized clinical trials. JAMA. 2015;314(5):489-500.

7. Lewis C, Roberts NP, Gibson S, Bisson JI. Dropout from psychological therapies for post-traumatic stress disorder (PTSD) in adults: systematic review and meta-analysis. Eur J Psychotraumatol. 2020;11(1):1709709.

8. Stein MB, Rothbaum BO. 175 Years of progress in PTSD therapeutics: learning from the past. Am J Psychiatry. 2018;175(6):508-516.

9. US Department of Veterans Affairs. PTSD: National Center for PTSD. Accessed June 3, 2024. https://www.ptsd.va.gov/understand/common/common_adults.asp