Neurocrine Biosciences has commenced a Phase 3 registrational study to evaluate osavampator as an adjunctive treatment for major depressive disorder (MDD) in adults. The trial aims to assess the efficacy, safety, and tolerability of the investigational drug in individuals who have shown an inadequate response to existing antidepressant therapies.
The Phase 3 program will enroll adult patients diagnosed with recurrent MDD or persistent depressive disorder who have not responded adequately to oral antidepressants during their current episode. Participants must have been on a stable dose of an oral antidepressant for at least eight weeks and agree to continue the same regimen throughout the study. Key inclusion criteria also require a total Hamilton Depression Rating Scale-17 Item (HAM-D17) score of ≥22 at screening and baseline.
Osavampator: A Novel Approach to MDD Treatment
Osavampator, formerly known as NBI-1065845, is a potential first-in-class alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) positive allosteric modulator (PAM). It is designed to enhance neuronal signals and improve synaptic transmission by increasing the AMPA receptor's sensitivity to glutamate. Neurocrine Biosciences holds an exclusive license for osavampator from Takeda Pharmaceutical Company Limited, excluding Japan.
Promising Phase 2 Results
In April 2024, Neurocrine Biosciences announced positive topline data from the Phase 2 SAVITRI study, which evaluated osavampator in adult participants with MDD. The study met its primary and secondary endpoints, demonstrating statistically significant changes from baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) total score at both day 28 (primary) and day 56 (secondary). One dose of osavampator showed an improvement over placebo of -4.3 (P = 0.0159) and -7.5 (P = 0.0016) at day 28 and day 56, respectively. Another dose also showed a trend toward improvement over placebo of -3.0 (P = 0.0873) and -3.6 (P = 0.1082) at day 28 and day 56, respectively. The most common adverse event was headache, with a safety profile comparable to placebo.
Addressing Unmet Needs in MDD Treatment
"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," said Eiry W. Roberts, M.D., Chief Medical Officer at Neurocrine Biosciences. "More than a third of those MDD sufferers endure debilitating symptoms that current treatment options cannot fully resolve."
Maurizio Fava, M.D., Chair of Mass General Brigham Academic Medical Centers Department of Psychiatry, emphasized the need for new strategies: "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. 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."
