New Positive Phase 2 Data on Osavampator for Major Depressive Disorder

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A new phase 2 study from Neurocrine Biosciences showed statistically significant and clinically meaningful improvement in depression severity with daily administration of 1 mg osavampator (NBI-1065845).¹ The study met its primary and secondary endpoints in showing greater than 50% reduction in depression severity from baseline to day 28 and from baseline to day 56, as measured by the Montgomery-Asberg Depression Rating Scale (MADRS).

This phase 2, double-blind SAVITRI study included 183 adults 18 to 65 years old, randomized into placebo, osavampator 1 mg, and osavampator 3 mg groups. Participants received their assigned treatment once daily for 8 weeks. All participants had a primary diagnosis of major depressive disorder (MDD) and had an inadequate response (less than 50% improvement) to their current antidepressant treatment. The study met its primary endpoint, showing a statistically significant reduction in depression severity (as measured by MADRS total score) from baseline to day 28, compared with placebo (P=0.0159). A secondary efficacy endpoint was also met, with statistically significant reduction in MADRS score from baseline to day 56 (P=0.0016). At day 56, osavampator 1 mg maintained significance in reduction, while osavampator 3 mg showed favorable but ultimately nominal difference in reduction. Remission rates (MADRS total score of 10 or less) were statistically significant in the 1 mg osavampator group, while the 3 mg osavampator group showed numerical improvement but not statistical significance.

At both 1 mg and 3 mg doses, osavamaptor was generally well-tolerated, with no serious adverse events. The most commonly reported treatment-emergent adverse events which occurred in 5% or more of patients were headache and nasopharyngitis; rates of these adverse effects in treatment groups were similar to placebo. Other reported adverse effects in groups receiving osavampator include insomnia (n=1 (1 mg group), n=3 (3 mg group)), somnolence (n=3 (1 mg group)), and nausea (n=1 (1 mg group)).

Osavampator is an investigational selective positive allosteric modulator for alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-PAM).² The medication is being developed as a potential adjunct for adults with MDD who have a precious inadequate response to oral antidepressant therapy.

"Major depressive disorder is one of the most common mental health conditions, and up to half of patients do not get sufficient relief from their current antidepressant regimen," said Sanjay Keswani, MD, chief medical officer of Neurocrine Biosciences. "We are encouraged by these results that show osavampator may help address this unmet need by modulating AMPA receptor activity."

Based on these results and an exploratory post hoc exposure-response analysis, Neurocrine Biosciences will continue to evaluate the 1 mg osavampator daily dosing in phase 3 studies. The company has initiated registration for a phase 3 program, with 5 actively enrolling studies.

References

1. Neurocrine Biosciences presents positive new data from phase 2 study of osavampator in adults with major depressive disorder. Press release. September 22, 2025. Accessed September 23, 2025. https://www.prnewswire.com/news-releases/neurocrine-biosciences-presents-positive-new-data-from-phase-2-study-of-osavampator-in-adults-with-major-depressive-disorder-302562476.html

2. Freudenberg F, Reif-Leonhard C, Dawson GR, et al. All roads lead to glutamate: NMDA and AMPA receptors as targets for rapid-acting antidepressants. Pharmacol Res. 2025;220:107918.