Phase 2 SAVITRI Supports Use of NBI-1065845 in Major Depressive Disorder with Inadequate Response to Antidepressants

Data from the phase 2 SAVITRI study suggest use of a novel agent could provide symptom relief in patients with major depressive disorder who are struggling to achieve results with their current antidepressant medications.

A potential first-in-class, investigational alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid positive allosteric modulator from Neurocrine Biosciences Inc, use of NBI-1065845 was associated with a statistically significant change from baseline in Montgomery Åsberg Depression Rating Scale (MADRS) total score at both day 28 and day 56.

"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."

Of note, Neurocrine Biosciences and Takeda Pharmaceuticals entered a strategic collaboration in 2020 to develop and commercialize compounds in Takeda’s pipeline, including an exclusive license to NBI-1065845, formerly known as TAK-653. According to this agreement, Neurocrine Biosciences is responsible for developing and commercializing all compounds included in the collaboration and for compounds other than NBI-1065845 and NBI-1065846.

Launched in 2022, the SAVITRI trial was a phase 2 randomized, double-blind, placebo-controlled, dose-finding study aimed at assessing the efficacy and safety of NBI-1065845 in adult patients with major depressive disorder. Conducted at 41 sites in 6 countries, the trial enrolled 183 patients with a primary diagnosis of major depressive disorder who had inadequate response to current antidepressant treatment. These patients were randomized to low-dose NBI-1065845, high-dose NBI-1065845, or placebo therapy.

The primary outcome of interest for the trial was change in MADRS total score from baseline to day 28. The trial had multiple secondary outcomes of interest, including change from baseline in total MADRS score at day 7, 14, and 56.

Topline results announced by Neurocrine Biosciences on April 23, 2024 suggested one of the doses demonstrated an improvement over placebo of -4.3 (P = .0159) and -7.5 (P = .0016) at day 28 and day 56, respectively. According to Neurocrine Biosciences, safety analysis indicated NBI-1065845 was generally well-tolerated, with headaches the most common adverse events associated with use. The release noted the adverse event profile for both doses examined was comparable to placebo, with no deaths or serious adverse events and low discontinuation rates observed throughout the trial.

In their release, Neurocrine Biosciences highlighted plans to present full data at an upcoming scientific congress.

References:

1. Neurocrine Biosciences. Neurocrine Biosciences Reports positive phase 2 data for NBI-1065845 in adults with major depressive disorder. Neurocrine Biosciences. April 23, 2024. Accessed April 23, 2024. https://neurocrine.gcs-web.com/news-releases/news-release-details/neurocrine-biosciences-reports-positive-phase-2-data-nbi-1065845.
2. Study to Assess the Efficacy and Safety of NBI-1065845 in Adults With Major Depressive Disorder (MDD) (SAVITRI). Clinicaltrials.gov. Accessed April 23, 2024. https://clinicaltrials.gov/study/NCT05203341.