PRINCETON, N.J. & TOKYO--(BUSINESS WIRE)--Otsuka America Pharmaceutical, Inc., (OAPI) and Otsuka Pharmaceutical, Co., Ltd. (Otsuka) 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 yeari, ii, iii, iv. Most patients (>80%) with PTSD in the United States are in the civilian populationv, 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 bullyingvii, 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 reactivityix. 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 antidepressantsx.
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-HT2A receptors, as well as a partial agonist at serotonin 5-HT1A and dopamine D2 receptorsxi, xii.
INDICATIONS and IMPORTANT SAFETY INFORMATION for REXULTI® (brexpiprazole)
INDICATIONS:
REXULTI is a prescription medicine used:
- along with antidepressant medicines to treat major depressive disorder (MDD) in adults
- to treat schizophrenia in adults and children ages 13 years and older
- to treat agitation that may happen with dementia due to Alzheimer’s disease
REXULTI should not be used as an “as needed” treatment for agitation that may happen with dementia due to Alzheimer’s disease.
It is not known if REXULTI is safe and effective in children with MDD.
It is not known if REXULTI is safe and effective in children under 13 years of age with schizophrenia.
IMPORTANT SAFETY INFORMATION:
- Increased risk of death in elderly people with dementia-related psychosis. Medicines like REXULTI can raise the risk of death in elderly people who have lost touch with reality (psychosis) due to confusion and memory loss (dementia). REXULTI is not approved for the treatment of people with dementia-related psychosis without agitation that may happen with dementia due to Alzheimer’s disease.
- Increased risk of suicidal thoughts and actions. REXULTI and antidepressant medicines may increase suicidal thoughts and actions in pediatric patients and young adult patients, especially within the first few months of treatment or when the dose is changed. Depression and other mental illnesses are the most important causes of suicidal thoughts and actions. All patients on antidepressants and their families or caregivers should closely watch for new or worsening depression symptoms, especially sudden changes in mood, behaviors, thoughts, or feelings. Report any change in these symptoms immediately to the doctor.
Do not take REXULTI if you are allergic to brexpiprazole or any of the ingredients in REXULTI.
REXULTI may cause serious side effects, including:
- Cerebrovascular problems, including stroke, in elderly people with dementia-related psychosis that can lead to death.
- Neuroleptic malignant syndrome (NMS) is a serious condition that can lead to death. Call your healthcare provider or go to the nearest hospital emergency room right away if you have some or all of the following signs and symptoms of NMS: high fever; changes in your pulse, blood pressure, heart rate, and breathing; stiff muscles; confusion; increased sweating
- Uncontrolled body movements (tardive dyskinesia). REXULTI may cause movements that you cannot control in your face, tongue, or other body parts. Tardive dyskinesia may not go away, even if you stop taking REXULTI. Tardive dyskinesia may also start after you stop taking REXULTI.
- Problems with your metabolism such as:
- high blood sugar (hyperglycemia) and diabetes. Increases in blood sugar can happen in some people who take REXULTI. Extremely high blood sugar can lead to coma or death. Your healthcare provider should check your blood sugar before you start, or soon after you start REXULTI and then regularly during long term treatment with REXULTI.
Call your healthcare provider if you have any of these symptoms of high blood sugar during treatment with REXULTI:
- feel very thirsty
- feel very hungry
- feel sick to your stomach
- need to urinate more than usual
- feel weak or tired
- feel confused, or your breath smells fruity
- increased fat levels (cholesterol and triglycerides) in your blood. Your healthcare provider should check the fat levels in your blood before you start, or soon after you start REXULTI, and then periodically during treatment with REXULTI.
- weight gain. You and your healthcare provider should check your weight before you start and often during treatment with REXULTI.
- Unusual and uncontrollable (compulsive) urges. Some people taking REXULTI have had strong unusual urges, to gamble and gambling that cannot be controlled (compulsive gambling). Other compulsive urges include sexual urges, shopping, and eating or binge eating. If you or your family members notice that you are having new or unusual strong urges or behaviors, talk to your healthcare provider.
- Low white blood cell count. Your healthcare provider may do blood tests during the first few months of treatment with REXULTI.
- Decreased blood pressure (orthostatic hypotension) and fainting. You may feel dizzy, lightheaded or pass out (faint) when you rise too quickly from a sitting or lying position.
- Falls. REXULTI may make you sleepy or dizzy, may cause a decrease in your blood pressure when changing position (orthostatic hypotension), and can slow your thinking and motor skills which may lead to falls that can cause fractures or other injuries.
- Seizures (convulsions).
- Problems controlling your body temperature so that you feel too warm. Do not become too hot or dehydrated during treatment with REXULTI. Do not exercise too much. In hot weather, stay inside in a cool place if possible. Stay out of the sun. Do not wear too much clothing or heavy clothing. Drink plenty of water.
- Difficulty swallowing that can cause food or liquid to get into your lungs.
- Sleepiness, drowsiness, feeling tired, difficulty thinking and doing normal activities. Do not drive a car, operate machinery, or do other dangerous activities until you know how REXULTI affects you. REXULTI may make you feel drowsy.
Before taking REXULTI, tell your healthcare provider about all of your medical conditions, including if you:
- have or have had heart problems or a stroke
- have or have had low or high blood pressure
- have or have had diabetes or high blood sugar or a family history of diabetes or high blood sugar.
- have or have had high levels of total cholesterol, LDL cholesterol, or triglycerides, or low levels of HDL cholesterol
- have or have had seizures (convulsions)
- have or have had kidney or liver problems
- have or have had a low white blood cell count
- are pregnant or plan to become pregnant. REXULTI may harm your unborn baby. Taking REXULTI during your third trimester of pregnancy may cause your baby to have abnormal muscle movements or withdrawal symptoms after birth. Talk to your healthcare provider about the risk to your unborn baby if you take REXULTI during pregnancy.
- Tell your healthcare provider if you become pregnant or think you are pregnant during treatment with REXULTI.
- There is a pregnancy exposure registry for women who are exposed to REXULTI during pregnancy. If you become pregnant during treatment with REXULTI, talk to your healthcare provider about registering with the National Pregnancy Registry for Psychiatric Medications. You can register by calling 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/.
- are breastfeeding or plan to breastfeed. It is not known if REXULTI passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with REXULTI.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. REXULTI and other medicines may affect each other causing possible serious side effects. REXULTI may affect the way other medicines work, and other medicines may affect how REXULTI works. Your healthcare provider can tell you if it is safe to take REXULTI with your other medicines. Do not start or stop any medicines during treatment with REXULTI without first talking to your healthcare provider.
The most common side effects of REXULTI include weight gain, sleepiness, dizziness, common cold symptoms, and restlessness or feeling like you need to move (akathisia).
These are not all the possible side effects of REXULTI. For more information, ask your healthcare provider or pharmacist.
You are encouraged to report side effects of REXULTI (brexpiprazole). Please contact Otsuka America Pharmaceutical, Inc. at 1-800-438-9927 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).
Please read FULL PRESCRIBING INFORMATION, including BOXED WARNING, and MEDICATION GUIDE for REXULTI.
About Otsuka
Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: Otsuka–people creating new products for better health worldwide. Otsuka researches, develops, manufactures, and markets innovative products, with a focus on pharmaceutical products to meet unmet medical needs and nutraceutical products for the maintenance of everyday health.
In pharmaceuticals, Otsuka is a leader in the challenging areas of mental, renal, and cardiovascular health and has additional research programs in oncology and on several under-addressed diseases including tuberculosis, a significant global public health issue. These commitments illustrate how Otsuka is a “big venture” company at heart, applying a youthful spirit of creativity in everything it does.
Otsuka established a presence in the U.S. in 1973 and today its U.S. affiliates include Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) and Otsuka America Pharmaceutical, Inc. (OAPI). These two companies’ 2,250 employees in the U.S. develop and commercialize medicines in the areas of mental health and nephrology, using cutting-edge technology to address unmet healthcare needs.
OPDC and OAPI are indirect subsidiaries of Otsuka Pharmaceutical Co., Ltd., which is a subsidiary of Otsuka Holdings Co., Ltd. headquartered in Tokyo, Japan. The Otsuka group of companies employed 34,400 people worldwide and had consolidated sales of approximately USD 14.2 billion in 2023.
All Otsuka stories start by taking the road less traveled. Learn more about Otsuka in the U.S. at www.otsuka-us.com and connect with us on LinkedIn and Twitter at @OtsukaUS. Otsuka Pharmaceutical Co., Ltd.’s global website is accessible at https://www.otsuka.co.jp/en/.
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i Kessler RC, Petukhova M, Sampson NA, Zaslavsky AM, Wittchen H -U. Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. Int J Methods Psychiatr Res. 2012;21(3):169-184.
ii Lehavot K, Katon JG, Chen JA, Fortney JC, Simpson TL. Post-traumatic Stress Disorder by Gender and Veteran Status [published correction appears in Am J Prev Med. 2019 Oct;57(4):573]. Am J Prev Med. 2018;54(1):e1-e9.
iii Lancaster CL, Teeters JB, Gros DF, Back SE. Posttraumatic Stress Disorder: Overview of Evidence-Based Assessment and Treatment. J Clin Med. 2016;5(11):105.
iv U.S. Department of Veterans Affairs. How Common Is PTSD in Adults? Last updated: Feb. 3, 2023. Last accessed: April 30, 2024. Available at: https://www.ptsd.va.gov/understand/common/common_adults.asp
v Davis LL, Schein J, Cloutier M, et al. The Economic Burden of Posttraumatic Stress Disorder in the United States From a Societal Perspective. J Clin Psychiatry. 2022;83(3):21m14116.
vi Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication [published correction appears in Arch Gen Psychiatry. 2005 Jul;62(7):768. Merikangas, Kathleen R [added]]. Arch Gen Psychiatry. 2005;62(6):593-602.
vii American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA, American Psychiatric Association, 2013
viii American Psychiatric Association. What is Posttraumatic Stress Disorder (PTSD)? Last updated: November 2022. Last accessed: August 28, 2024. Available at: https://www.psychiatry.org/patients-families/ptsd/what-is-ptsd.
ix Wang PS, Berglund P, Olfson M, Pincus HA, Wells KB, Kessler RC. Failure and delay in initial treatment contact after first onset of mental disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):603-613.
x U.S. Department of Veterans Affairs. VA/DoD Clinical Practice Guidelines. Management of Posttraumatic Stress Disorder and Acute Stress Disorder. Provider Summary 2023. Version 4.0. www.healthquality.va.gov/guidelines/MH/ptsd/VA-DoD-CPG-PTSD-Provider-Summary.pdf
xi REXULTI® (brexpiprazole). Prescribing Information. FDA.
xii Maeda K, Sugino H, Akazawa H, et al. Brexpiprazole I: in vitro and in vivo characterization of a novel serotonin-dopamine activity modulator. J Pharmacol Exp Ther. 2014;350(3):589-604.
Contacts
Otsuka in the U.S.
Robert Murphy
Corporate Communications
Otsuka America Pharmaceutical, Inc.
robert.murphy@otsuka-us.com
+1 609 249 7262
Otsuka outside the U.S.
Jeffrey Gilbert
Leader, Pharmaceutical PR
Otsuka Pharmaceutical Co., Ltd.
Gilbert.jeffrey.a@otsuka.co.jp
