Positive Phase 2 Data for NBI-1065845 in Adults With Major Depressive Disorder

kieferpix/AdobeStock

Neurocrine Biosciences released new positive topline data for the phase 2, randomized, double-blind, placebo-controlled, dose-finding SAVITRI study that assessed the efficacy and safety of NBI-1065845 in adults with major depressive disorder (MDD).¹

NBI-1065845—an investigational alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) positive allosteric modulator (PAM)—is in development as a potential treatment for patients with MDD who have seen adequate response to at least 1 antidepressant in their current depressive episode.

“Many millions of people living with major depressive disorder do not benefit fully from currently available treatments and experience persistent debilitating symptoms,” said Eiry W. Roberts, MD, chief medical officer at Neurocrine Biosciences. “NBI-1065845 has the potential to be a first-in-class treatment to alleviate many of these symptoms of MDD. The phase 2 data from the SAVITRI study are very encouraging, and we look forward to meeting with the FDA to discuss a path into phase 3 studies.”

Investigators enrolled 183 adults with a primary diagnosis of MDD and who had inadequate response to current antidepressant treatment. The study met its primary and key secondary endpoints—namely that a once-daily, oral administration of NBI-1065845 produced a statistically significant change from baseline in Montgomery Åsberg Depression Rating Scale (MADRS) total score at (1) day 28, the primary endpoint and (2) day 56, the secondary endpoint. In the full analysis data set, the least squares mean differences from baseline in MADRS total score for NBI-1065845 were an improvement over placebo of -4.3 (P = 0.0159) and -7.5 (P = 0.0016) at day 28 and day 56, respectively, for one of the doses; and 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, for another dose.

NBI-1065845 was generally well tolerated, with the most common adverse event being headache. The adverse event profile for both doses of NBI-1065845 were comparable to placebo. There were no deaths or serious adverse events. The discontinuation rates were low throughout the study.

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

This positive news comes at the heels of the failure of a similar asset in November 2023. Neurocrine halted the phase 2 development of NBI-1065846 in MDD after the study missed its primary endpoint, which looked at the change in severity of anhedonia. While no further development with NBI-1065846 is planned at this time, Neurocrine and Takeda will continue to collaborate on several clinical development programs, including NBI-1065845, but also luvadaxistat for the treatment of cognitive impairment associated with schizophrenia in phase 2 development, and NBI-1070770 for the treatment of MDD in phase 1 development.²

Learn more about other in-development treatments for major depressive disorder here:

-First Patient Dosed in Phase 2 Clinical Trial of NBI-1070770 for MDD

-ALTO-203 for Major Depressive Disorder and Anhedonia: Phase 2 Study Initiated

-BPL-003: Rapid, Durable Treatment for TRD Sees Positive Phase 2 Results

References

1. Neurocrine Biosciences reports positive phase 2 data for NBI-1065845 in adults with major depressive disorder. News release. April 23, 2024. https://www.prnewswire.com/news-releases/neurocrine-biosciences-reports-positive-phase-2-data-for-nbi-1065845-in-adults-with-major-depressive-disorder-302123889.html

2. Neurocrine Biosciences provides development pipeline update. News release. November 9, 2023. Accessed April 23, 2024. https://neurocrine.gcs-web.com/news-releases/news-release-details/neurocrine-biosciences-provides-development-pipeline-update