A “Surprise” Miss: NBI-1070770 for Major Depressive Disorder Fails in Phase 2 Study

Neurocrine Biosciences announced that its phase 2 study evaluating the efficacy, safety, and tolerability of NBI-1070770 in adults with major depressive disorder (MDD) did not meet the primary endpoint compared to placebo. Investigators of this signal-seeking study enrolled 73 adult participants with a diagnosis of MDD who did not adequately respond to at least 1 antidepressant in their current course of treatment.

NBI-1070770 is an investigational selective, orally active, negative allosteric modulator of the NR2B subunit-containing N-methyl-D-aspartate receptor.

"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, MD, the chief medical officer of Neurocrine Biosciences. "We are grateful to the patients, investigators and site staff who participated in this trial."

The phase 2, multicenter, randomized, double-blind, placebo-controlled study was designed to evaluate the efficacy, safety, and tolerability of 3 dosage strengths of adjunctive NBI-1070770 compared with placebo (1:1:1:3) on improving symptoms of depression in adults with MDD who have had an inadequate response to at least 1 antidepressant. Participants aged 18 to 65 years were randomly assigned to receive either NBI-1070770 or placebo for 4 weeks during the double-blind treatment period. The primary objective of the study was to assess the change from baseline to day 5 in depression severity, as measured by the Montgomery-Åsberg Depression Rating Scale. Neurocrine noted that NBI-1070770 was generally well tolerated, but was unable to significantly improve depression severity and failed to distinguish itself from placebo.

In a statement to investors, analysts shared this mid-stage failure “comes as a surprise,” especially given NBI-1070770’s mechanism of action. They also stated that there is an “inherent risk in neuropsychiatric clinical development,” and seemingly “higher rates of failure” in the neuropsychiatric space than in other therapeutic fields.²

Neurocrine obtained development and commercialization rights for NBI-1070770 from Takeda Pharmaceutical Company back in June 2020, when the 2 companies inked a $2 billion dollar deal to develop and commercialize molecules in Takeda’s early-to-mid-stage psychiatry pipeline.³

Back in April 2024, the first patient was dosed in phase 2 development. At that time, the chief medical officer at Neurocrine Biosciences, Eiry W. Roberts, MD, said that, “The selectivity of NBI-1070770 for the NMDA NR2B receptor has the potential to benefit patients who have moderate to severe depression.”⁴

“Our team will continue to analyze these results so we can determine appropriate next steps,” concluded Keswani.¹

References

1. Neurocrine Biosciences provides update on phase 2 study of NBI-1070770 in adults with major depressive disorder. News release. November 10, 2025. Accessed November 11, 2025. https://neurocrine.gcs-web.com/news-releases/news-release-details/neurocrine-biosciences-provides-update-phase-2-study-nbi-1070770

2. Manalac T. Neurocrine’s depression drug delivers ‘surprise’ phase II miss. BioSpace. November 11, 2025. Accessed November 11, 2025. https://www.biospace.com/drug-development/neurocrines-depression-drug-delivers-surprise-phase-ii-miss

3. Neurocrine and Takeda ink $2 billion-plus neuroscience development deal. June 16, 2020. Accessed November 11, 2025. https://www.biospace.com/neurocrine-and-takeda-partner-to-focus-on-psychiatry-drugs

4. Neurocrine Biosciences announces first-patient dosed in phase 2 clinical study evaluating NBI-1070770 in adults with major depressive disorder. BioSpace. News release. April 3, 2024. Accessed November 11, 2025. https://www.biospace.com/article/releases/neurocrine-biosciences-announces-first-patient-dosed-in-phase-2-clinical-study-evaluating-nbi-1070770-in-adults-with-major-depressive-disorder/