AbbVie Submits sNDA to FDA for Vraylar (Cariprazine) as Adjunctive Treatment for Major Depressive Disorder

News on February 22, 2022 /BioValleyBIOON/ -- AbbVie recently announced that it has submitted to the U.S. Food and Drug Administration (FDA) Submitted a Supplemental New Drug Application (NDA) for Vraylar (cariprazine):As an adjunctive therapy for the treatment of severe cases receiving antidepressant therapyDepression(MDD) patients。If approved, this would be the fourth indication for Vraylar.

Cariprazine is an orally administered, once-daily atypical antipsychotic drug, marketed under the brand name Vraylar in the United States and Reagila in Europe. In the U.S., the drug was approved for marketing in 2015, and its current indications include: (1) for the acute treatment of manic or mixed episodes in adult patients with bipolar I disorder (3-6 mg/day); (2) for the treatment of depressive episodes in adult patients with bipolar I disorder (1.5 or 3 mg/day); (3) for the treatment of schizophrenia in adults (1.5-6.0 mg/day).

This sNDA is based on previously announcedClinical TrialResults. Phase 3 Study 3111-301-001 showed,Compared with placebo, patients receiving Vraylar 1.5mg/day showed clinically and statistically significant changes in Montgomery-Asberg Depression Rating Scale (MADRS) total scores from baseline to Week 6 (p=0.0050).Phase 2/3 RGH-MD-75 study shows,Patients receiving flexible doses of Vraylar 2.0-4.5 mg/day showed clinically and statistically significant changes in MADRS total scores from baseline to Week 8 compared to placebo (p=0.0114) when given in addition to ongoing antidepressant therapy (ADT).In these two studies, the safety data were consistent with the established safety profile of Vraylar for its various indications, and no new safety events were identified. The sNDA was also supported by data from the RGH-MD-76 study, which evaluated the long-term safety and tolerability of Vraylar over a 26-week treatment period.

SevereDepression(MDD) is one of the most common and severe mental disorders, with more than half of patients never achieving satisfactory treatment outcomes. Based on available research data, Vraylar has the potential to benefit these patients as an adjunctive therapy.

Vraylar-cariprazine Chemical Structure (Source: medchemexpress.com)

Major Depressive Disorder (MDD) is a common condition affecting 19 million people of all ages in the United States. The World Health Organization (WHO) has ranked depression as the third leading cause of disability worldwide and a major contributor to the global burden of disease. Symptoms of MDD include depressed mood, loss of pleasure or interest in activities, changes in appetite or weight, sleep disturbances, psychomotor agitation, loss of energy, feelings of worthlessness, indecisiveness, and suicidal thoughts. In the U.S., the average age of onset for MDD is 26 years, and MDD represents an estimated economic burden of $211 billion.

Clinical TrialEvaluated the efficacy and safety of cariprazine for a broad range of psychiatric disorders.

Although the mechanism of action is not fully understood, cariprazine may exert its effects through a combination of partial antagonism at central dopamine D2 and serotonin 5-HT1A receptors, along with agonist activity at serotonin 5-HT2A receptors.Pharmacodynamic studies show that cariprazine, as a partial agonist, can bind with high affinity to dopamine D3, dopamine D2, and 5-HT1A receptors. In in vitro studies, cariprazine's affinity for the D3 receptor is 8 times that of the D2 receptor. Meanwhile, cariprazine can also act as an antagonist, showing high/moderate affinity for serotonin 5-HT2B, 5-HT2A, and histamine H1 receptors, but has lower affinity for 5-HT2C and α1A-adrenergic receptors, and no significant affinity for adrenergic receptors. The clinical significance of these in vitro study data is currently unclear. (Bioon.com)

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