New Positive Results for NBI-1117568 in Adults With Schizophrenia

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Neurocrine Biosciences announced positive top-line data for its phase 2 clinical study of NBI-1117568 (NBI-'568) in adults with schizophrenia—the first investigational, oral, muscarinic M4 selective agonist in development for the treatment of schizophrenia.¹

The phase 2, multicenter, randomized, double-blind, placebo-controlled, multi-arm, multi-stage inpatient dose-finding study (NCT05545111) assessed the efficacy, safety, tolerability, and pharmacokinetics of NBI-'568 when compared with placebo in 210 adult participants with a primary diagnosis of schizophrenia who are experiencing an acute exacerbation or relapse of symptoms.² The study met its primary endpoint for the once-daily 20 mg dose of NBI-'568, which was demonstrating a clinically meaningful and statistically significant reduction from baseline in the Positive and Negative Syndrome Scale (PANSS) total score at week 6 with a placebo-adjusted mean reduction of 7.5 points (p=0.011 and effect size of 0.61) and an 18.2-point reduction from baseline. This once-daily 20 mg dose also demonstrated a statistically significant improvement for secondary endpoints, such as improvement in the Clinical Global Impression of Severity (CGI-S) scale, Marder Factor Score – Positive Symptom Change, and Marder Factor Score – Negative Symptom Change.

"NBI-‘568 demonstrated a clinically meaningful and statistically significant reduction in PANSS scores and was well tolerated, importantly with minimal gastrointestinal effects and no weight gain relative to placebo," said Maurizio Fava, MD, psychiatrist-in-chief at Massachusetts General Hospital of Harvard University. "As a selective M4 orthosteric agonist, the potential of NBI-‘568 as an option that could reduce symptoms of schizophrenia with fewer side effects would be a welcome alternative to current treatments for patients and caregivers."

As to safety profile, NBI-'568 was generally safe and well tolerated at all doses studied. Treatment discontinuation rates due to adverse events were similar between NBI-'568 and placebo. Adverse events with the highest incidence were somnolence, dizziness, and headache. Gastrointestinal adverse events such as nausea and constipation were low in frequency and similar to placebo. Additionally, cardiovascular-related events were low in frequency and deemed to have clinical relevance at any dose tested. Notably, NBI-'568 was not associated with a greater increase in weight than placebo. Very few extrapyramidal symptoms adverse events were reported.

"This phase 2 dose-finding study delivered on our goal of identifying a once-daily, well tolerated dosing regimen with a compelling and competitive benefit-risk profile," said Eiry W. Roberts, MD, chief medical officer at Neurocrine Biosciences. "We recognize the significant need for new and innovative medicines to treat schizophrenia and look forward to advancing NBI-'568, the first M4 selective agonist, into phase 3 development early next year."

References

1. Neurocrine Biosciences reports positive phase 2 data for NBI-1117568 in adults with schizophrenia. News release. PR Newswire. August 28, 2024. https://finance.yahoo.com/news/neurocrine-biosciences-reports-positive-phase-110000753.html

2. Efficacy, safety, tolerability, and pharmacokinetics of NBI-1117568 in adults with schizophrenia. ClinicalTrials.gov. Updated September 18, 2023. Accessed August 28, 2024. https://clinicaltrials.gov/study/NCT05545111