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.
‘It is with great pleasure to know that the label extension of cariprazine in the USA has been submitted,’ - said Gábor Orbán, Chief Executive Officer of Richter. ‘We are confident that our partner AbbVie will co-operate with the FDA to bring a potential new adjunctive therapy to people suffering from MDD while undergoing antidepressant treatment and seeking additional symptom relief.’
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
More information can be found on www.clinicaltrials.gov (NCT03738215, NCT01469377, NCT01838876).
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 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.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).
Gedeon Richter Plc., headquartered in Budapest/Hungary, is a major pharmaceutical company in Central Eastern Europe, with an expanding direct presence in Western Europe, in China and in Latin America. Having reached a market capitalization of EUR 3.8 billion (USD 4.7billion) by the end of 2020, Richter's consolidated sales were approximately EUR 1.6 billion (USD 1.8 billion) during the same year. The product portfolio of Richter covers many important therapeutic areas, including Women's Healthcare, Central Nervous System and Cardiovascular areas. Having the largest R&D unit in Central Eastern Europe, Richter's original research activity focuses on CNS disorders. With its widely acknowledged steroid chemistry expertise, Richter is a significant player in the Women's Healthcare field worldwide. Richter is also active in biosimilar product development.
For further information:
Katalin Ördög: +36 1 431 5680
Zsuzsa Beke: +36 1 431 4888