Osavampator (NBI-1065845/TAK-653) Demonstrates Meaningful Improvements in Depression Severity and Is Well Tolerated in Adults With Major Depressive Disorder: Phase 2 SAVITRI Results

Osavampator (NBI-1065845/TAK-653), a selective positive allosteric modulator of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPA-PAM), was evaluated in adults with major depressive disorder (MDD).

This phase 2, multicenter, randomized, double-blind, placebo-controlled study was conducted in adults (18–65 years) with MDD and an inadequate response to ≥1 antidepressant treatment in the current episode (SAVITRI, NCT05203341). Participants were randomized 2:1:1 to placebo, osavampator 1 mg, or osavampator 3 mg, administered once-daily for 8 weeks. Key endpoints included changes in depression severity from baseline to Day 28 and Day 56 assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Secondary efficacy and safety/tolerability endpoints were also evaluated.

Of 183 participants randomized, 161 (88%) completed study treatment. At Day 56, osavampator 1 mg showed statistically significant improvement in MADRS total score versus placebo (least-squares mean difference [95% confidence interval, CI] −6.9 [−11.2, −2.6]; nominal p=0.0018; effect size 0.73), which was already evident at Day 28 (least-squares mean difference [95% CI] −4.3 [−7.8, −0.8]; nominal p=0.0159). A numerical improvement was observed for osavampator 3 mg versus placebo at Day 56 (nominal p=0.0573). Participants receiving osavampator 1 mg were more likely to achieve response and remission at Day 56. Osavampator (both doses) was well tolerated, with no deaths, serious adverse events, or adverse events of special interest.

Osavampator 1 mg resulted in a clinically meaningful and statistically significant improvement in depression severity versus placebo. Osavampator was well tolerated, with no clinically significant safety concerns. These results support further investigation of osavampator for MDD treatment.