Otsuka Pharmaceutical, Co. Ltd. (Otsuka) and Otsuka America Pharmaceutical, Inc., (OAPI) announce that the U.S. Food and Drug Administration (FDA) plans to host a Psychopharmacologic Drugs Advisory Committee (PDAC) meeting to seek input on issues related to the Supplemental New Drug Application (sNDA) for brexpiprazole in combination with sertraline for the treatment of adults with post-traumatic stress disorder (PTSD).

The FDA's decision to host a PDAC meeting does not reflect a final decision on the approvability. A final date for the meeting has yet to be set by the FDA, but it is currently anticipated to occur during the first half of 2025.

This decision means that the Prescription Drug User Fee Act (PDUFA) target action date, originally planned for February 8, 2025, will be delayed.

About Post-Traumatic Stress Disorder

PTSD is one of the most common mental health disorders in the United States, with approximately five percent of the population affected during a given year^i,ii,iii,,iv. Most patients (>80%) with PTSD in the United States are in the civilian population^v,vi. It may occur in people who have experienced or witnessed a traumatic event, series of events or set of circumstances. An individual may experience an event that is emotionally or physically harmful or life-threatening and which may affect mental, physical, social, and/or spiritual well-being. Examples of traumatic events include physical/sexual assault, natural disasters, serious accidents, terrorist acts, war/combat, historical trauma, intimate partner violence and bullying^vii,viii.

Symptoms of PTSD are generally grouped into four symptom clusters: intrusion (re-experiencing), avoidance, negative cognitions and mood, and marked alterations in arousal and reactivity^ix. Individual symptom type and intensity can fluctuate over time and between individuals. The average time from index trauma to symptom presentation is typically 2.2 years, and the average time from index trauma to PTSD diagnosis is typically 8.7 years. To meet the criteria for PTSD diagnosis, symptoms must last longer than one month, and they must be severe enough to interfere with aspects of daily life, such as relationships or work. Symptoms also must not be due to medications, substance use, or another medical condition. Guideline-recommended first-line treatment includes psychotherapy (e.g., cognitive behavioral therapy) and first line pharmacotherapy options include certain antidepressants^x.

About brexpiprazole

Brexpiprazole was approved in the U.S. by FDA in 2015, as an adjunctive therapy to antidepressants in adults with major depressive disorder (MDD) and as a treatment for schizophrenia in adults. Most recently, brexpiprazole was approved in the U.S. for the treatment of agitation associated with dementia due to Alzheimer's disease, in May 2023. Brexpiprazole was also approved by Health Canada for schizophrenia and adjunctive treatment of MDD in 2017 and 2019, respectively, and for agitation associated with dementia due to Alzheimer's disease in 2024. It was approved by the European Medicines Agency in 2018 for the treatment of schizophrenia and the Ministry of Health, Labour and Welfare in Japan for the treatment of schizophrenia and MDD in 2018 and 2023, respectively.

In 2024, Japan's Ministry of Health, Labour and Welfare also approved brexpiprazole for the treatment of excessive motor activity or physically/verbally aggressive behavior due to rapid changes in mood, irritability, and/or outbursts associated with dementia due to Alzheimer's disease.

Brexpiprazole was discovered by Otsuka and is being co-developed by Otsuka and Lundbeck. The mechanism of action of brexpiprazole is unknown. Brexpiprazole has high receptor binding affinity to norepinephrine, serotonin and dopamine receptors. It is an antagonist at norepinephrine α1B and α2C receptors and serotonin 5-HT_2A receptors, as well as a partial agonist at serotonin 5-HT_1A and dopamine D2 receptors^xi,xii.