Skip to main content

AbbVie Submits Supplemental New Drug Application to U.S. FDA for cariprazine (VRAYLAR) for the Adjunctive Treatment of Major Depressive Disorder

NORTH CHICAGO, Ill., Feb. 22, 2022. AbbVie today announced that it has submitted a supplemental New Drug Application (sNDA) for cariprazine (VRAYLAR) to the U.S. Food and Drug Administration (FDA) for the adjunctive treatment of major depressive disorder (MDD) in patients who are receiving ongoing antidepressant therapy. The submission is supported by results from previously announced clinical trials.

A Phase 3 Study 3111-301-001 showed a clinically and statistically significant change from baseline to week six in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score for patients treated with cariprazine at 1.5 mg/day compared with placebo. A second registration-enabling study, RGH-MD-75, showed a clinically and statistically significant change from baseline to week eight in the MADRS total score for patients treated with cariprazine at 2-4.5 mg/day compared with placebo. In both of these studies, safety data were consistent with the established safety profile of cariprazine across indications, with no new safety events identified. Also supporting the submission is study RGH-MD-76 that examined the long-term safety and tolerability of cariprazine over 26 weeks.

"Many people living with major depressive disorder struggle to find a treatment that reduces their depressive symptoms, with many taking years to find the right treatment. Cariprazine, when added to ongoing antidepressant treatment in patients with major depressive disorder, demonstrated that it can reduce depressive symptoms," said Michael Severino, M.D., vice chairman and president, AbbVie. "We look forward to working closely with the FDA during the review of our submission to bring a potential new adjunctive therapy to patients with major depressive disorder who are taking an antidepressant and seeking additional relief. This submission demonstrates our strong commitment to addressing additional gaps in the care of people affected by psychiatric disorders."

Cariprazine is marketed as VRAYLAR in the United States and is FDA-approved to treat adults with depressive, acute manic and mixed episodes associated with bipolar I disorder, as well as schizophrenia. Cariprazine is being 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.

About Major Depressive Disorder (MDD)
MDD is one of the most common mental disorders in the United States. In 2020, an estimated 21 million adults had at least one major depressive episode. For some individuals, MDD can result in severe impairment which may interfere with or limit one's daily activities.1 The World Health Organization lists depression as the third-leading cause of disability worldwide and as a major contributor to the overall global burden of disease. Symptoms can include depressed mood, loss of pleasure or interest in activities, changes in appetite or weight, changes in sleep, psychomotor retardation, loss of energy, feelings of worthlessness, indecisiveness, and recurrent thoughts of death.2 In the United States, the estimated economic burden of MDD has been estimated to be around $326 billion.3

About Study 3111-301-001
Study 3111-301-001 is a randomized, double-blind, placebo-controlled, multicenter trial with 759 participants conducted in 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. Preliminary study findings were announced on October 29th, 2021 and will be presented at a future medical meeting.

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 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.4

About Study RGH-MD-76
Study RGH-MD-76 is a long-term, multi-center, open label, flexible-dose safety and tolerability study with 347 participants, conducted in the United States. The study had one treatment group that received caripriazine 1.5-4.5 mg/d + ADT for 26 weeks. Patients entering from the 8-week lead-in study continued ADT at their lead-in study dose; new patients continued their protocol-allowed ADT. On day 1, cariprazine was initiated at 0.5 mg/day; the dosage was increased by 0.5 mg/day until the target dose of 3.0 mg/day was received on days 6 and 7. Dosages could be decreased to 1.5 mg/day for tolerability reasons at any time beginning at week 1 or increased to 4.5 mg/day for inadequate response between weeks 2 and 10. Data from Study RGH-MD-76 were published in International Clinical Psychopharmacology.5

About VRAYLAR (cariprazine)
VRAYLAR is an oral, once-daily atypical antipsychotic approved for the acute treatment of adults with manic or mixed episodes associated with bipolar I disorder (3 to 6 mg/day) and for the treatment of depressive episodes associated with bipolar I disorder (bipolar depression) in adults (1.5 or 3 mg/day). VRAYLAR is also approved for the treatment of schizophrenia in adults (1.5 to 6 mg/day). Use of VRAYLAR in adjunctive treatment of major depressive disorder is not approved and its safety and efficacy have not been evaluated by regulatory authorities.

While the mechanism of action of VRAYLAR is unknown, the efficacy of VRAYLAR could be mediated through a combination of partial agonist activity at central dopamine Dâ‚‚ 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.6 The clinical significance of these in vitro data is unknown.

VRAYLAR is being 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).

Forward-Looking Statements
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.

References:

  1. Substance Abuse and Mental Health Services Administration. Key substance use and mental health indicators in the United States: Results from the 2020 National Survey on Drug Use and Health. Center for Behavioral Health Statistics and Quality. 2021. https://www.samhsa.gov/data/. Accessed February 1, 2022.
  2. World Health Organization. Depression. Fact Sheet. 2021. Available at: https://www.who.int/news-room/fact-sheets/detail/depression. Accessed February 1, 2022>.
  3. Greenberg P, Fournier AA, Sistsky T, et al. Pharmacoeconomics. 2021;39(6):653-65.
  4. Durgam S, Earley W, Guo H, et al. Efficacy and safety of adjunctive cariprazine in inadequate responders to antidepressants: a randomized, double-blind, placebo-controlled study in adult patients with major depressive disorder. J Clin Psychiatry. 2016;77(3):371-8. doi: 10.4088/JCP.15m10070.
  5. Vieta E, Earley W, Burgess M, et al. Long-term safety and tolerability of cariprazine as adjunctive therapy in major depressive disorder. International Clinical Psychopharmacology. 2019;34(2)76-83. doi: 10.1097/YIC.0000000000000246
  6. AbbVie. VRAYLAR (cariprazine) [package insert]. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/204370s006lbl.pdf. Revised January 2019. Accessed February 15, 2022.

SOURCE AbbVie

Posted: February 2022

More news resources

Subscribe to our newsletter

Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.