Neurocrine Biosciences Launches Phase 3 Registration Program for Osavampator in Major Depressive Disorder

Neurocrine Biosciences today announced the launch of a phase 3 pivotal trial program for osavampator, an investigational drug under development as an adjunctive treatment to antidepressants for individuals with major depressive disorder (MDD) with inadequate response to previous therapy.1 The company announced positive topline data for the phase 2 SAVITRI study of osavampator in adults in April 2024.2

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Osavampator is a potential first in class alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) positive allosteric modulator (PAM) in development for treatment of adults with MDD who have not benefited from treatment with at least one antidepressant in their current episode of depression, according to the Neurocrine press release.1 Through binding to an allosteric site on the AMPA receptor, a PAM will increase the receptor’s sensitivity to glutamate, enhancing neuronal signals and improving synaptic transmission.3

Interest in the potential role for direct modulation of the glutamatergic system as a novel approach for treating MDD has risen significantly over the past 20 years, driven in part by the positive findings for and recent approval of esketamine for the disorder.3

"Major depressive disorder is a condition that has a profound effect on patients and their families and is associated with significant morbidity and mortality," Maurizio Fava, MD, chair, Mass General Brigham Academic Medical Centers Department of Psychiatry,” said in the Neurocrine statement.1 "The great majority of patients suffering from major depressive disorder do not achieve a sustained remission of their condition and the options for next step strategies to help them are quite limited."1

The phase 3 program will evaluate the efficacy, safety, and tolerability of oral osavampator compared with placebo taken once daily on improving symptoms in adults with MDD from baseline as assessed by standard depression rating scales to day 56 of treatment.4

Eligible participants will have a primary diagnosis of MDD or persistent depressive disorder with poor response to an oral antidepressant in the current depressive episode. A participant will have been taking the medication for at least 8 weeks and be willing to continue the treatment regimen throughout the phase 3 study.4

In the 183-particiapnt phase 2 SAVITRI study, osavampator met its primary and secondary endpoints and was generally well tolerated. The novel agent produced a statistically significant change from baseline in Montgomery Åsberg Depression Rating Scale (MADRS) total score at both Day 28 (primary) and Day 56 (secondary). The most common adverse event (AE) was headache, according to Neurocrine. The AE profile was similar for the study drug and placebo and study discontinuation rates were low.2

Neurocrine plans to share additional data from the SAVITRI study at a future scientific conference.

"Osavampator has the potential to become a first-in-class treatment for MDD, a disorder that impacts more than 21 million people in the United States," Eiry W. Roberts, MD, chief medical officer, Neurocrine Biosciences, said in the announcement. "More than a third of those MDD sufferers endure debilitating symptoms that current treatment options cannot fully resolve."1

“This trial is happening at a time when it is clear that, as a field, we need to develop new augmentation strategies to enhance the efficacy of standard antidepressants," Mass General’s Fava concluded.1

1. Neurocrine Biosciences announces initiation of a phase 3 registrational program for osavampator as an adjunctive therapy for treatment of major depressive disorder in adults. News release. Neurocrine Biosciences. January 28, 2025. Accessed January 28, 2025. https://neurocrine.gcs-web.com/news-releases/news-release-details/neurocrine-biosciences-announces-initiation-phase-3

2. Neurocrine Biosciences reports positive phase 2 data for NBI-1065854 in adults with major depressive disorder. News release. Neurocrine Biosciences. April 23, 2024. Accessed January 25, 2025. https://neurocrine.gcs-web.com/news-releases/news-release-details/neurocrine-biosciences-reports-positive-phase-2-data-nbi-1065845

3. Kadriu B, Musazzi L, Johnston JN, et al. Positive AMPA receptor modulation in the treatment of neuropsychiatric disorders: a long and winding road. Drug Discov Today. 2021;26(12):2816-2838. doi: 10.1016/j.drudis.2021.07.027

4. Study to assess the efficacy and safety of NBI-1065854 as an adjunctive treatment in participants with major depressive disorder (MDD). ClinicalTrials.gov ID: NCT06786624. Updated January 27, 2025. Accessed January 28, 2025. https://clinicaltrials.gov/study/NCT06786624