NORTH CHICAGO, Ill., Dec. 16, 2022 AbbVie (NYSE: ABBV) today announced that the U.S. Food and Drug Administration (FDA) has approved VRAYLAR® (cariprazine) as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) in adults. Supported by clinical data demonstrating efficacy and well-established tolerability, this additional indication provides a new option for adults who have a partial response to the treatment of an antidepressant.
“Many living with major depressive disorder find that their ongoing antidepressant therapy doesn’t offer meaningful relief from the symptoms they experience every day,” said Thomas Hudson, M.D., senior vice president, research and development, chief scientific officer, AbbVie. “Today’s approval of VRAYLAR provides an important new treatment option to meet a critical unmet medical need. AbbVie is committed to driving progress and advancing solutions for patients living with complex neuropsychiatric conditions.”
MDD is one of the most common mental disorders in the U.S.; approximately one in five adults will experience this disorder during their lifetime.1 In a large U.S. study of adults with MDD, approximately 50 percent still had depressive symptoms with their first antidepressant.2 If some symptoms of depression persist while on an antidepressant, adding a different type of medication, often referred to as an adjunctive treatment, to the existing regimen may help.
“Patients with inadequate response to standard antidepressant medication are often frustrated by the experience of trying multiple medicines and still suffering from unresolved symptoms. Instead of starting over with another standard antidepressant, VRAYLAR works with an existing treatment and can help build on the progress already made,” said Gary Sachs, MD, clinical vice president at Signant Health, associate clinical professor of psychiatry at Massachusetts General Hospital, and lead Phase 3 clinical trial investigator. “For adults living with major depressive disorder, because of inadequate improvement in response to standard antidepressants, VRAYLAR is an efficacious adjunctive treatment option with a well-characterized safety profile.”
Cariprazine is marketed as VRAYLAR® in the U.S., and in addition to being approved as an adjunctive therapy to antidepressants for the treatment of MDD in adults, it is FDA-approved to treat adults with depressive, acute manic and mixed episodes associated with bipolar I disorder, as well as schizophrenia. Cariprazine is co-developed by AbbVie and Gedeon Richter Plc. More than 8,000 patients worldwide have been treated with cariprazine across more than 20 clinical trials evaluating the efficacy and safety of cariprazine for a broad range of psychiatric disorders.
“When we were in the early stages of development for cariprazine, we focused on designing a compound that covers a range of symptoms for mental health conditions and affects the dopamine D3 receptor,” said István Greiner, Ph.D., research and development, director, Gedeon Richter. “While schizophrenia and bipolar manic and mixed episodes were the first indications in the U.S. market, we are thrilled to see the full potential of cariprazine unlocked with approvals in bipolar I depression, and now, as an antidepressant adjunct in major depressive disorder.”
Highlights from the clinical program supporting the approval include:
About Major Depressive Disorder (MDD)
MDD is one of the most common mental disorders in the U.S., characterized by symptoms such as overwhelming feelings of sadness and/or loss of interest that don’t go away after two weeks.3 MDD can cause severe functional impairment, adversely affect interpersonal relationships, and may impact the quality of life.4 It is a leading cause of disability in the world,5 and has a lifetime prevalence of 20% for adults in the U.S.1 Symptoms can include depressed mood, loss of pleasure or interest in activities, feelings of worthlessness, lack of energy, poor concentration, appetite changes, sleep disturbances, suicidal thoughts, and feeling restless or moving or talking more slowly.3 In the U.S., the estimated economic burden of MDD has been estimated to be around $326 billion in 2020.6
About Study 3111-301-001
Study 3111-301-001 is a randomized, double-blind, placebo-controlled, multicenter trial with 751 participants conducted in the United States, Bulgaria, Estonia, Germany, Hungary, Ukraine and the United Kingdom. Following a screening period of up to 14 days, patients with an inadequate clinical response to their antidepressant monotherapy (ADT) were randomized into three treatment groups (1:1:1). The first group received cariprazine 1.5 mg/day + ADT, the second group received cariprazine 3.0 mg/day + ADT, and the third group received placebo + ADT. For six weeks, the medication was given once daily in addition to the ongoing ADT treatment. Patients treated with cariprazine 3.0 mg/day + ADT demonstrated improvement in MADRS total score at week six over placebo + ADT but did not meet statistical significance.
About Study RGH-MD-75
Study RGH-MD-75 is a randomized, double-blind, placebo-controlled, flexible-dose, outpatient, multicenter trial with 808 participants, conducted in the United States, Estonia, Finland, Slovakia, Ukraine and Sweden. After 7-14 days of screening and washout of prohibited medications, eligible patients entered an 8-week, double-blind treatment period in which they continued antidepressant treatment and were randomized (1:1:1) to adjunctive cariprazine 1-2 mg/day, cariprazine 2-4.5 mg/day, or placebo. Data from Study RGH-MD-75 were published in the Journal of Clinical Psychiatry.7 Patients treated with cariprazine 1-2 mg/day + ADT demonstrated improvement in MADRS total score at week eight over placebo + ADT but did not meet statistical significance.
About VRAYLAR® (cariprazine)
VRAYLAR is an oral, once-daily atypical antipsychotic approved as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) in adults (1.5 or 3 mg/day), for the treatment of depressive episodes associated with bipolar I disorder (bipolar depression) in adults (1.5 or 3 mg/day), and for the acute treatment of adults with manic or mixed episodes associated with bipolar I disorder (3 to 6 mg/day). VRAYLAR is also approved for the treatment of schizophrenia in adults (1.5 to 6 mg/day).
While the mechanism of action of VRAYLAR is unknown, the efficacy of VRAYLAR is thought to be mediated through a combination of partial agonist activity at central dopamine D₂ and serotonin 5-HT1A receptors and antagonist activity at serotonin 5-HT2A receptors. Pharmacodynamic studies with VRAYLAR have shown that it may act as a partial agonist with high binding affinity at dopamine D3, dopamine D2, and serotonin 5-HT1A receptors. VRAYLAR demonstrated up to ~8-fold greater in vitro affinity for dopamine D3 vs D2 receptors. VRAYLAR also acts as an antagonist at serotonin 5-HT2B and 5-HT2A receptors with high and moderate binding affinity, respectively as well as it binds to the histamine H1 receptors. VRAYLAR shows lower binding affinity to the serotonin 5-HT2C and α1A- adrenergic receptors and has no appreciable affinity for cholinergic muscarinic receptors.8 The clinical significance of these in vitro data is unknown.
VRAYLAR is developed jointly by AbbVie and Gedeon Richter Plc, with AbbVie responsible for commercialization in the U.S., Canada, Japan, Taiwan and certain Latin American countries (including Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Mexico, Peru and Venezuela).
Visit www.vraylar.com for more information.
VRAYLAR® (cariprazine) Uses and Important Safety Information
VRAYLAR is a prescription medicine used in adults:
What is the most important information I should know about VRAYLAR?
Elderly people with dementia-related psychosis (having lost touch with reality due to confusion and memory loss) taking medicines like VRAYLAR are at an increased risk of death. VRAYLAR is not approved for treating patients with dementia-related psychosis.
VRAYLAR and antidepressants may increase suicidal thoughts or actions in some children and young adults 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. Patients on antidepressants and their families or caregivers should watch for new or worsening depression symptoms, especially sudden changes in mood, behaviors, thoughts, or feelings. This is very important when VRAYLAR or the antidepressant is started or when the dose is changed. Report any change in these symptoms immediately to the doctor.
VRAYLAR may cause serious side effects, including:
Who should not take VRAYLAR?
Do not take VRAYLAR if you are allergic to any of its ingredients. Get emergency medical help if you are having an allergic reaction (eg, rash, itching, hives, swelling of the tongue, lip, face or throat).
What should I tell my healthcare provider before taking VRAYLAR?
Tell your healthcare provider about any medical conditions and if you:
Tell your healthcare provider about all medicines that you take, including prescriptions, over-the-counter medicines, vitamins, and supplements. VRAYLAR may affect the way other medicines work, and other medicines may affect how VRAYLAR works. Do not start or stop any medicines while taking VRAYLAR without talking to your healthcare provider.
What are the most common side effects of VRAYLAR?
These are not all possible side effects of VRAYLAR.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
If you are having difficulty paying for your medicine, AbbVie may be able to help. Visit AbbVie.com/myAbbVieAssist to learn more.
About AbbVie in Mental Health
AbbVie is driving the pursuit of better mental health. Over the last 30 years, the company's scientists and clinicians have worked to tackle the complexity of mental illness and today offer a portfolio of medicines and a pipeline of innovation that spans depression, anxiety, bipolar I disorder, and schizophrenia. To learn more about AbbVie's work to support individuals throughout their mental health journey, please visit www.abbvie.com or follow @abbvie on Twitter, Facebook, Instagram, YouTube and LinkedIn.
AbbVie's mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women's health and gastroenterology, in addition to products and services across our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com.
Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, failure to realize the expected benefits from AbbVie's acquisition of Allergan plc ("Allergan"), failure to promptly and effectively integrate Allergan's businesses, competition from other products, challenges to intellectual property, difficulties inherent in the research and development process, adverse litigation or government action, changes to laws and regulations applicable to our industry and the impact of public health outbreaks, epidemics or pandemics, such as COVID-19. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2021 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.
1 Hasin DS, Sarvet AL, Meyers JL, et al. Epidemiology of Adult DSM-5 Major Depressive Disorder and Its Specifiers in the United States. JAMA Psychiatry. 2018;75(4):336-346.
2 Trivedi MH, Rush AJ, Wisniewski SR, et al. Am J Psychiatry. 2006;163(1):28-40.
3 National Institute of Mental Health (2022). Depression. Available at: https://www.nimh.nih.gov/health/topics/depression. Accessed December 2022.
4 Bains N, Abdijadid S. Major Depressive Disorder. [Updated 2022 Jun 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available at: https://www.ncbi.nlm.nih.gov/books/NBK559078/. Accessed December 2022.
5 Friedrich MJ. Depression Is the Leading Cause of Disability Around the World. JAMA. 2017;317(15):1517.
6 Greenberg P, Fournier AA, Sistsky T, et al. Pharmacoeconomics. 2021;39(6):653-65.
7 Durgam S, Earley W, Guo H, et al. J Clin Psychiatry. 2016;77(3):371-8.
8 VRAYLAR. Package insert. Allergan USA, Inc; 2022.
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