Lykos Therapeutics Announces FDA Acceptance and Priority Review of New Drug Application for MDMA-Assisted Therapy for PTSD

• PDUFA date is August 11, 2024 
• If approved, this would be the first MDMA-assisted therapy and psychedelic-assisted therapy

SAN JOSE, Calif., Feb. 9, 2024 /PRNewswire/ -- Lykos Therapeutics (formerly MAPS Public Benefit Corporation) ("Lykos"), a company dedicated to transforming mental healthcare, announced that the U.S. Food and Drug Administration ("FDA") has accepted its new drug application ("NDA") for midomafetamine capsules ("MDMA") used in combination with psychological intervention, which includes psychotherapy (talk therapy) and other supportive services provided by a qualified healthcare provider for individuals with post-traumatic stress disorder ("PTSD"). The FDA has granted the application priority review and has assigned a Prescription Drug User Fee Act ("PDUFA") target action date of August 11, 2024. If approved, this would be the first MDMA-assisted therapy and psychedelic-assisted therapy.

"Securing priority review for our investigational MDMA-assisted therapy is a significant accomplishment and underscores the urgent unmet need for new innovation in the treatment of PTSD," said Amy Emerson, chief executive officer of Lykos Therapeutics. "We remain focused on working with the FDA through the review process and preparing for a controlled launch with an emphasis on quality should this potential treatment be approved."

The NDA submission included results from numerous studies including two randomized, double-blind, placebo-controlled Phase 3 studies (MAPP1 and MAPP2) evaluating the efficacy and safety of MDMA used in combination with psychological intervention versus placebo with therapy in participants diagnosed with severe or moderate to severe PTSD, respectively. Both MAPP1 and MAPP2 studies met their primary and secondary endpoints and were published in Nature Medicine. ^{1, 2} The primary endpoint for both studies was to assess changes in PTSD symptom severity as measured by the change from baseline in Clinician-Administered PTSD Scale for DSM-5 ("CAPS-5"). The key secondary endpoint of both studies was to assess improvement in functional impairment associated with PTSD as measured by the change from baseline in the Sheehan Disability Scale ("SDS"). No serious adverse events were reported in the MDMA group in either study.

The FDA grants priority review for drugs that, if approved, would represent significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications.³

MDMA-assisted therapy has not been approved by any regulatory agency. The safety and efficacy of MDMA-assisted therapy has not been established for the treatment of PTSD. Investigational MDMA-assisted therapy is also being studied in other indications.

About PTSD
PTSD is a serious mental health condition that can develop when a person experiences or witnesses a traumatic event. ⁴ PTSD affects approximately 13 million Americans each year⁵ with women and disadvantaged or marginalized groups more likely to be affected. ⁶ Military personnel also have a greater prevalence of PTSD than the general population⁷ however, it may not be as widely known that that the largest cause of PTSD is non-combat-related trauma (e.g., sexual violence, unexpected death of a loved one, life-threatening traumatic event or interpersonal violence). ⁸ PTSD results in debilitating symptoms including nightmares and intrusive thoughts related to the trauma, mental and/or physical distress in response to trauma-related stimuli, avoidant behaviors, negative thoughts and feelings, and hyperarousal. ^{9, 10} These symptoms can impact nearly all aspects of a person's life.[11] People with PTSD frequently also experience anxiety, depression, substance use disorder and suicidal ideation. ^12,13 They also may have a greater incidence of medical conditions that impact their physical health, including heart disease, metabolic syndrome and asthma. ^{14, 15, 16, 17} In addition to the significant personal impact, PTSD has an enormous economic impact resulting in an annual cost of over $232 billion in the United States.¹⁸

PTSD Treatment
Trauma-focused talk therapy, which concentrates on memories of the traumatic event or thoughts and feelings associated with the traumatic event ¹⁹ is first-line treatment for PTSD , which can be used alone or in combination with medication. There are two SSRIs approved for the treatment of PTSD (sertraline and paroxetine). ²⁰ Studies have shown talk therapy lessens the severity of PTSD symptoms, however improvements in functioning and quality of life have been modest. ^21,22 Trauma-focused talk therapy is associated with a high risk of dropout and lingering symptoms which occur in as many as two-thirds of people who complete treatment. ^{23, 24} Current treatments for PTSD are "reasonably efficacious" (Bryant, 2019, p.265), however many people don't respond to treatment or stop treatment early, underscoring the urgent need for new evidence-based therapies and approaches to address this important public health issue. ²⁵ While there have been advancements in the management of PTSD, there have been no new drug treatments approved by the FDA in over twenty years.²⁶

About MDMA-Assisted Therapy
MDMA (3,4-methylenedioxymethamphetamine) is not new to mental health professionals. MDMA is an entactogen— a class of psychoactive compounds that are differentiated from classic psychedelics (i.e., psilocybin, mescaline and LSD) and are defined based on their mechanism and known effects of increasing self-awareness leading to introspection and personal reflection.^27,,28 In the 1970's and early 1980's MDMA was used in conjunction with talk therapy by mental health providers to enhance patients' access, processing, and communication of difficult emotions and experiences.²⁹ In 1985, the U.S. Drug Enforcement Administration ("DEA") made MDMA a Schedule I drug under the Controlled Substances Act preventing it from being used for recreational or medical use. ³⁰ Since then, research has shown the unique properties of MDMA allow it to act as a powerful catalyst to support psychotherapy by helping diminish the brain's fear response allowing people to access and process painful memories without being overwhelmed. ³¹ However, additional clinical trials would be needed to secure regulatory review and potential approval. 

Lykos, with longstanding roots in advocacy for psychedelic medicine, pioneered the first randomized, double-blind, placebo controlled clinical trials evaluating the efficacy and safety of MDMA-assisted therapy as an investigational modality using midomafetamine (MDMA) in combination with psychological intervention to treat PTSD.

With a growing body of evidence supporting the potential medical use of MDMA, in 2017 the FDA granted the company's investigational MDMA-assisted therapy Breakthrough Therapy designation, a process designed to expedite the development and review of drugs intended to treat serious conditions for which preliminary scientific evidence indicates that it may demonstrate a substantial improvement over available therapies. If approved by the FDA, the U.S. Drug Enforcement Administration ("DEA") would be required to reschedule MDMA making it available for prescription medical use.

Lykos Therapeutics (Formerly MAPS PBC)
At Lykos, formerly MAPS PBC, our mission is to transform mental healthcare. We aspire to challenge the status quo through the development of novel therapies and therapeutic approaches to treat mental health conditions. With 30+ years of experience researching psychedelic-assisted therapies, we remain committed to the rigorous pursuit of evidence-based development of novel approaches. Founded in 2014 by the non-profit MAPS, Lykos is a for-profit public benefit corporation ("PBC") established to further the development of investigational psychedelic-assisted therapies. As a PBC, we consider the impact of our decisions on society just as we think about financial implications. Everything we do is viewed through a public benefit lens. To learn more visit us at www.lykospbc.com and on LinkedIn, X, Instagram and Facebook.

¹ Mitchell JM, Bogenschutz M, Lilienstein A, et al. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med 609 2021;27:1025–33
² Mitchell JM, Ot'alora MG et al. MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Nat Med. 2023 Sept 14 doi: 10.1038/s41591-023-02565-4. Online ahead of print.
³ FDA Priority Review. Available at: https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review. Accessed January 2024.
⁴ The Mayo Clinic, PTSD, Symptoms and Causes www.mayoclinic.org/diseases-conditions/post-traumatic-stress-disorder/symptoms-causes/syc-20355967c. Accessed January 2024.
⁵ VA National Center for PTSD. US Department of Veterans Affairs. Accessed February 14, 2023. https://www.ptsd.va.gov/understand/common/common_adults.asp
⁶ Goldstein RB et al. Soc Psychiatry Psychiatr Epidemiol. 2016; 51(8):1137–1148.
⁷ Lehavot K, et al. Am J Prev Med. 2018;54(1):e1-e9.
⁸ Kessler RC, Rose S, Koenen KC, et al. How well can post-traumatic stress disorder be predicted from pre-trauma risk factors? An exploratory study in the WHO World Mental Health Surveys. World Psychiatry. 2014 Oct;13(3):265-74. doi: 10.1002/wps.20150. PMID: 25273300; PMCID: PMC4219068.
⁹ Davis LL. The economic burden of posttraumatic stress disorder in the United States from a societal perspective. J Clin Psychiatry. (2022) Apr 25;83(3):21m14116. doi: 10.4088/JCP.21m14116.
¹⁰ Bryant RA. Post-traumatic stress disorder: a state-of-the-art review of evidence and challenges. World Psychiatry. 2019;18(3):259–269.
¹¹ The Mayo Clinic, PTSD, Symptoms and Causes www.mayoclinic.org/diseases-conditions/post-traumatic-stress-disorder/symptoms-causes/syc-20355967c
¹² Grinage B.D. Diagnosis and Management of Post-traumatic Stress Disorder. Am Fam Physician. (2003);68(12):2401-2409.
¹³ Rojas SM et al. Understanding PTSD comorbidity and suicidal behavior: associations among histories of alcohol dependence, major depressive disorder, and suicidal ideation and attempts. J Anxiety Disord. 2014;28(3):318–325.
¹⁴ Edmondson D, von Känel R. Post-traumatic stress disorder and cardiovascular disease. Lancet Psychiatry. 2017;4(4):320–329.
¹⁵ Krantz DS et al. Post-traumatic stress disorder (PTSD) as a systemic disorder: Pathways to cardiovascular disease. Health Psychol. 2022;41(10):651–662.
¹⁶ Boscarino, JA. Posttraumatic Stress Disorder and Mortality Among U.S. Army Veterans 30 Years After Military Service. Ann Epidemiol. 2006;16(4):248–256.
¹⁷ Nichter B et al. Physical health burden of PTSD, depression, and their comorbidity in the U.S. veteran population: Morbidity, functioning, and disability. J Psychosom Res 2019;124:109744.
¹⁸ Davis LL. The economic burden of posttraumatic stress disorder in the United States from a societal perspective. J Clin Psychiatry. (2022) Apr 25;83(3):21m14116. doi: 10.4088/JCP.21m14116.
¹⁹ Watkins LE, Sprang KR, Rothbaum BO. Treating PTSD: A Review of Evidence-Based Psychotherapy Interventions. Front Behav Neurosci. 2018 Nov 2;12:258. doi: 10.3389/fnbeh.2018.00258. PMID: 30450043; PMCID: PMC6224348.
²⁰ American Psychological Association. Clinical Practice Guidelines for the Treatment of PTSD. Medications (apa.org) Accessed February 5, 2024.
²¹ Cusack K, et al. Psychological treatments for adults with posttraumatic stress disorder: A systematic review and meta-analysis. Clin Psychol Rev. 2016;43:128-141.
²² Bonfils, KA et al, Functional outcomes from psychotherapy for people with posttraumatic stress disorder: A meta-analysis. J Anxiety Disorders. 2022;89:102576.
²³ Lewis, C., Roberts, N. P., Gibson, S., & Bisson, J. I. (2020). Dropout from psychological therapies for post-traumatic stress disorder (PTSD) in adults: systematic review and meta-analysis. European Journal of Psychotraumatology, 11(1). https://doi.org/10.1080/20008198.2019.1709709
²⁴ Steenkamp, M. M., Litz, B. T., Hoge, C. W., & Marmar, C. R. (2015). Psychotherapy for Military-Related PTSD. JAMA, 314(5), 489. https://doi.org/10.1001/jama.2015.8370
²⁵ Bryant RA. Post-traumatic stress disorder: a state-of-the-art review of evidence and challenges. World Psychiatry. 2019;18(3):259–269.
²⁶ Stein MB, Rothbaum BO. 175 Years of Progress in PTSD Therapeutics: Learning From the Past. Am J Psychiatry. 2018 Jun 1;175(6):508-516. doi: 10.1176/appi.ajp.2017.17080955. PMID: 29869547.
²⁷ Nichols, David E.Entactogens: How the Name for a Novel Class of Psychoactive Agents Originated. Frontiers in Psychiatry. Vol 13, 2022. DOI= 10.3389/fpsyt.2022.863088.
²⁸ Vollenweider, Franz X., Brain mechanisms of hallucinogens and entactogens. Dialogues Clin Neurosci. 2001 Dec; 3(4): 265–279.doi: 10.31887/DCNS.2001.3.4/fxvollenweider
²⁹ Wagner MT, Mithoefer MC, Mithoefer AT, MacAulay RK, Jerome L, Yazar-Klosinski B, Doblin R. Therapeutic effect of increased openness: Investigating mechanism of action in MDMA-assisted psychotherapy. J Psychopharmacol. 2017 Aug;31(8):967-974. doi: 10.1177/0269881117711712. Epub 2017 Jun 21. PMID: 28635375; PMCID: PMC5544120.
³⁰ National Institute on Drug Abuse What is the history of MDMA? | National Institute on Drug Abuse (NIDA) (nih.gov). Accessed, January 17, 2024. What is the history of MDMA? | National Institute on Drug Abuse (NIDA) (nih.gov)
³¹ Yazar-Klosinski B, Mithoefer MC. Potential Psychiatric Uses for MDMA. Clinical Pharmacology & Therapeutics, 2016 Nov 9. https://doi.org/10.1002/cpt.565

SOURCE Lykos Therapeutics