AbbVie has recently submitted a supplementary new drug application (sNDA) to the FDA for Vraylar (cariprazine) as the adjunctive treatment of major depressive disorder (MDD). However, pricey Vraylar will have to compete with low-cost aripiprazole and quetiapine generics, with competition becoming even fiercer when generic brexpiprazole enters the market in 2026, according to GlobalData, a leading data and analytics company.

The sNDA is supported by data from three late-stage clinical trials: RGH-MD-75, 3111-301-001, and RGH-MD-76*. If approved, Vraylar is anticipated to generate sales of $741.2m in the MDD market across the US, 5EU (France, Germany, Italy, Spain, and the UK), Japan, and Canada.

Christie Wong, Pharma Analyst at GlobalData comments: “Vraylar has had a series of successes and disappointments in its late-stage clinical trials for MDD. While the drug showed clinically and statistically significant efficacy in RGH-MD-75 and 3111-301-001, it failed to meet the primary endpoint in the Phase III study, 3111-302-001 (NCT03739203). Furthermore, in study 3111-301-001, although patients responded to Vraylar doses of 1.5 mg/day, patients treated with 3.0 mg/day did not show a statistically significant improvement in depressive symptoms over placebo.”

Despite this mixed data, GlobalData anticipates substantial uptake of Vraylar as an adjunctive treatment for MDD. Key opinion leaders (KOLs) interviewed by GlobalData confirmed that some physicians are already using Vraylar off-label as an adjunctive therapy to selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs).

Wong adds: “Vraylar will have to compete with the some of the most successful adjunctive therapies in the MDD market—Otsuka’s Abilify (aripiprazole), AstraZeneca’s Seroquel (quetiapine), and Otsuka/Lundbeck’s Rexulti (brexpiprazole)—all atypical antipsychotics approved for MDD.

“KOLs echoed that Vraylar might struggle in the MDD market as a ‘me-too’ atypical antipsychotic with a higher cost of therapy. However, there is the opportunity for AbbVie to conduct a head-to-head trial against other atypical antipsychotics to help differentiate its product and promote its uptake, given that the efficacy data for Vraylar has been mixed.”

Looking at the pipeline, GlobalData notes that the adjunctive therapies for MDD will face even more competition in the future. Four other late-stage pipeline products are being developed as adjunctive therapies for MDD and are expected to enter the market over the next decade. These products are: Sage Therapeutics’/Biogen’s zuranolone, Janssen’s seltorexant, Intra-Cellular Therapies’ Caplyta (lumateperone), and Relmada Therapeutics’ dextromethadone (REL-1017).

Wong concludes: “Many of these pipeline products have novel mechanisms of action that will help them compete in a highly crowded market space.”

*In RGH-MD-75 (NCT01469377), patients treated with Vraylar at 2–4.5 mg/day demonstrated a clinically and statistically significant change from baseline to week eight in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score when compared with placebo. Furthermore, in 3111-301-001 (NCT03738215), patients treated with Vraylar at 1.5 mg/day showed a clinically and statistically significant change from baseline to week six in the MADRS total score when compared with placebo. Long-term safety and tolerability of Vraylar over 26 weeks was demonstrated in the Phase III RGH-MD-76 study (NCT01838876).