Neurocrine Biosciences announced that its Phase II clinical trial evaluating NBI-1070770 in adults with major depressive disorder (MDD) did not achieve its primary endpoint when compared to placebo. The study, which enrolled 73 patients, aimed to assess changes in depression severity from baseline to day five using the Montgomery-Åsberg Depression Rating Scale (MADRS).
Despite missing the primary endpoint, the investigational compound was generally well-tolerated across all tested dosage levels, according to the company's announcement.
Trial Design and Patient Population
The randomized, multi-center, double-blind, placebo-controlled study evaluated three different doses of adjunctive NBI-1070770 versus placebo using a 1:1:1:3 allocation ratio. Participants aged 18 to 65 years with a diagnosis of major depressive disorder were enrolled, specifically those who had shown inadequate response to at least one antidepressant during their current treatment episode.
The four-week treatment period was designed as a signal-seeking study to evaluate the efficacy, safety, and tolerability of the investigational compound as an adjunctive therapy.
Mechanism of Action and Development Background
NBI-1070770 is a selective, orally active negative allosteric modulator (NAM) targeting the NR2B subunit-containing N-methyl-D-aspartate (NMDA NR2B) receptor. This mechanism represents a novel approach to treating major depressive disorder, distinct from traditional antidepressant therapies.
Neurocrine Biosciences acquired the development and commercialization rights for NBI-1070770 from Takeda Pharmaceutical Company, adding the compound to its neuroscience-focused pipeline.
Clinical Context and Unmet Need
Major depressive disorder is characterized by persistent low mood, diminished energy, impaired concentration, and lack of interest, among other debilitating symptoms. According to the World Health Organization, MDD ranks among the leading causes of disability globally and presents an increased risk of suicide and self-harm while being associated with increased all-cause mortality.
The condition affects more than 21 million people in the United States, with approximately half of patients failing to achieve adequate relief from their first antidepressant treatment, highlighting the significant unmet medical need for novel therapeutic approaches.
Company Response and Future Plans
"While we are disappointed that NBI-1070770 did not meet the primary endpoint, there are aspects of the data that warrant further exploration," said Sanjay Keswani, M.D., Chief Medical Officer at Neurocrine Biosciences. "Our team will continue to analyze these results so we can determine appropriate next steps."
Keswani expressed gratitude to the patients, investigators, and site staff who participated in the trial, acknowledging their contribution to advancing depression research.
The company indicated that a more comprehensive analysis of the trial data is ongoing, which will inform decisions regarding the future development pathway for NBI-1070770 in major depressive disorder.
