PDAC voted 2 yes to 9 no on the question of whether the available data show that midomafetamine is effective in patients with PTSD. They also voted 1 yes to 10 no on the question of whether the benefits of midomafetamine with FDA's proposed risk evaluation and mitigation strategy (REMS) outweigh its risks for the treatment of patients with PTSD. The FDA is not bound by PDAC's guidance but takes its advice into consideration.
The role of PDAC is to provide the FDA with independent, expert advice and recommendations based on their review and evaluation of data concerning the safety and effectiveness of investigational medicines for use in the practice of psychiatry and related fields.1 The FDA's approval decision is expected by the Prescription Drug User Fee Act ("PDUFA") target action date of August 11, 2024.
"We are disappointed in today's vote given the urgent unmet need in PTSD and appreciate that the committee faced a challenging and atypical assignment, which was to evaluate a therapeutic approach that combines drug therapy (MDMA) and psychological intervention," Amy Emerson, Chief Executive Officer of Lykos Therapeutics.
"We remain committed to working with the FDA to address outstanding questions so that we may find a path forward to ensure the responsible and careful introduction of MDMA-assisted therapy into the healthcare system, if approved. We are grateful to the advocates, clinical trial participants and people living with PTSD who shared their testimony in the open public hearing and through written comments, and will continue to do everything we can to bring this potential new therapeutic option to people living with PTSD."
PDAC's review included results from 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, which includes psychotherapy (talk therapy) and other supportive services provided by a qualified healthcare provider, versus placebo with psychological intervention 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.2,3
"PTSD can result in debilitating symptoms that can significantly impact nearly all areas of a person's life and while we have available treatments, unfortunately many people don't respond or stop treatment early, making today's decision an important step forward to identifying new and effective evidenced-based treatment options,"4,5 said Jerry Rosenbaum,
MD, Director of the Center for the Neuroscience of Psychedelics at Massachusetts General Hospital Research Institute and Stanley Cobb Professor of Psychiatry at Harvard Medical School. "Research has suggested the unique properties of MDMA may act as a catalyst to enhance psychotherapy, the current standard of care, by helping diminish the brain's fear and avoidance responses and extend the window of tolerance of painful emotions and memories, thereby allowing people to access and process painful memories without being overwhelmed."6
On February 9, 2024, the FDA accepted the company's NDA and granted the application Priority Review. 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.7
Midomafetamine (MDMA) capsules have not been approved by any regulatory agency. The safety and efficacy of midomafetamine have not been established for the treatment of PTSD. Investigational midomafetamine is also being studied in other indications.
About PTSD:
Prevalence and symptoms:
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 year with women and disadvantaged or marginalized groups more likely to be affected.8,9 Military personnel also have a greater prevalence of PTSD than the general population.10 However, it may not be as widely known 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).11 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.12 These symptoms can impact nearly all aspects of a person's life, including their interpersonal relationships.4 PTSD can also be a chronic condition with a World Health Organization study showing that after ten years post-trauma, nearly a quarter of people had not recovered.
PTSD Treatment:
Trauma-focused talk therapy, which concentrates on memories of the traumatic event or thoughts and feelings associated with the traumatic event, is first-line treatment for PTSD, which can be used alone or in combination with medication.21 There are two SSRIs approved for the treatment of PTSD (sertraline and paroxetine).22 Studies have shown talk therapy lessens the severity of PTSD symptoms, however, improvements in functioning and quality of life have been modest.23,24 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.25,26 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.27 While there have been advancements in the management of PTSD, there have been no new drug treatments approved by the FDA in over 20 years.28.
About MDMA-Assisted Therapy:
MDMA (midomafetamine) is commonly known to mental health professionals. In the 1970s and early 1980s MDMA was used in conjunction with talk therapy by mental health providers to help enhance patients' access, processing and communication of difficult emotions and experiences.29 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 demonstrated effects of increasing self-awareness leading to introspection and personal reflection.30,31
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.32 Since then, research has suggested that MDMA may have potential as a catalyst to support psychotherapy by helping diminish the brain's fear response, allowing people to access and process painful memories without being overwhelmed.33
Lykos, with longstanding roots in advocacy for psychedelic medicine, was the first company to pioneer 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 and submit a New Drug Application to the FDA seeking approval for the treatment of PTSD in adults. If approved by the FDA, the DEA would be required to reschedule MDMA making it available for prescription medical use.
Lykos Therapeutics:
At Lykos Therapeutics, a public benefit corporation (PBC) founded by MAPS, our mission is to transform mental healthcare. We're applying decades of evidence-based research to develop investigational psychedelics to catalyze therapeutic approaches for mental health conditions. We are relentlessly exploring and reimagining novel approaches to address unmet needs in the mental healthcare space, with an initial focus on PTSD. As a PBC, we are focused on delivering positive impact on our people, communities and society.
For more information please visit, www.lykospbc.com
