Phase 2 Data Supports the Effectiveness, Safety of NBI-1117568 for Schizophrenia

Neurocrine Biosciences announced on August 28, 2024, their phase 2 trial met its primary endpoint, demonstrating the effectiveness of NBI-1117568 for schizophrenia.

The once-daily 20 mg dose of NBI-1117568 provided a statistically significant 7.5-point improvement in the Positive and Negative Syndrome Scale (PANSS) Total Score compared to the placebo at week 6 (P = .011; effect size of 0.61) with an 18.2-point PANSS Total Score Improvement from Baseline.

“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, in a statement. "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.”

According to the World Health Organization, approximately 20 million people worldwide experience schizophrenia. Traditional treatment options for schizophrenia often rely on antipsychotic medications which may lead to short- and long-term health impacts. Thus, investigators wanted to study a novel treatment option for schizophrenia.

Investigators conducted a phase 2, multicenter, randomized, double-blind, placebo-controlled, multi-arm, multi-stage inpatient dose-finding study to assess the efficacy, safety, tolerability, and pharmacokinetics of NBI-1117568 compared with placebo in adult patients with schizophrenia. The study included 210 participants with schizophrenia who experienced an acute exacerbation or relapse of symptoms.

Other than meeting the primary endpoint, the once-daily 20 mg dose of NBI-1117568 also provided significant improvement for secondary endpoints, including the Clinical Global Impression of Severity (CGI-S) scale, Marder Factor Score – Positive Symptom Change, and Marder Factor Score – Negative Symptom Change.

The trial showed NBI-1117568 was safe and well-tolerated at all doses. Investigators observed similar treatment discontinuation rates due to adverse events between participants on NBI-1117568 and placebo. The most common adverse events observed included somnolence, dizziness, and headache.

Less common adverse events included nausea and constipation, cardiovascular-related events, and extrapyramidal symptoms. Gastrointestinal adverse events were similar in both arms, and cardiovascular-related events did not seem to have clinical relevance at any dose. NBI-1117568 was not associated with greater weight gain when compared to placebo.

“NBI-1117568 demonstrated a clinically meaningful and statistically significant reduction in PANSS scores and was well tolerated, importantly with minimal GI effects and no weight gain relative to placebo," said Maurizio Fava, Psychiatrist-in-Chief at Massachusetts General Hospital of Harvard University, in the press release. "As a selective M4 orthosteric agonist, the potential of NBI-1117568 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."

References

^{Neurocrine Biosciences Reports Positive Phase 2 Data for NBI-1117568 in Adults with Schizophrenia. PR Newswire. August 28, 2024. https://www.prnewswire.com/news-releases/neurocrine-biosciences-reports-positive-phase-2-data-for-nbi-1117568-in-adults-with-schizophrenia-302232261.html. Accessed August 28, 2024.}