Richter’s partner, AbbVie, today announced top-line results from two Phase 3 clinical trials, Study 3111-301-001 and Study 3111-302-001, evaluating the efficacy and safety of cariprazine (VRAYLAR®) as an adjunctive treatment for patients with major depressive disorder (MDD). In Study 3111-301-001, cariprazine showed a statistically significant change from baseline to week six in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score compared with placebo.

Patients treated with cariprazine at 1.5 mg/day achieved improved MADRS total score at week six compared to placebo (p-value=0.0050). Patients treated with cariprazine at 3.0 mg/day demonstrated improvement in MADRS total score at week six over placebo but did not meet statistical significance (p-value=0.0727). In Study 3111-302-001, cariprazine demonstrated numerical improvement in depressive symptoms from baseline to week six in MADRS total score compared with placebo but did not meet its primary endpoint for either the 1.5 mg/day or 3.0 mg/day dose.

In a previously published Phase 2/3 registration-enabling study, RGH-MD-75, patients treated with cariprazine flexible doses of 2.0-4.5 mg/day in addition to ongoing antidepressant therapy (ADT) met the primary endpoint and achieved improved MADRS total scores at week eight compared to placebo (p-value=0.0114).

Based on the positive results of studies 3111-301-001 and RGH-MD-75, and the totality of data reported, AbbVie intends to submit a supplemental New Drug Application (sNDA) with the U.S. Food and Drug Administration for the expanded use of cariprazine for the adjunctive treatment of MDD.

“We are proud that a second Phase III clinical study showed statistically significant and clinically relevant improvement for a large group of patients not adequately responding to existing treatment” – said Mr Gábor Orbán, CEO of Richter. “These results get us one step closer to a potential new adjunctive treatment option for major depressive disorder.”

The safety results of cariprazine in all three studies were consistent with its established safety profile across indications with no new safety signals identified. The most common adverse events occurring at >5% in the cariprazine groups during the six-week study period were akathisia, nausea, insomnia, headache and somnolence.

Full results from studies 3111-301-001 and 3111-302-001 will be presented at a future medical meeting.

MDD is a common condition with 19 million people of all ages affected in the United States.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 agitation, loss of energy, feelings of worthlessness, indecisiveness, and current thoughts of death.2 In the United States, the mean age of onset for the first episode is 26 years old,3 and MDD represents an estimated $211 billion economic burden.4

Cariprazine is marketed as VRAYLAR® in the United States and is FDA-approved to treat depressive, acute manic and mixed episodes associated with bipolar I disorder, as well as schizophrenia in adults. Cariprazine is being co-developed by Gedeon Richter Plc and AbbVie. 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. 


Full text of the release (with references) is available here.