The NBI-‘568-SCZ2028 dose-finding study successfully met its primary endpoint with the once-daily 20 mg dose. This dose showed a significant and clinically meaningful reduction in the Positive and Negative Syndrome Scale (PANSS) total score at Week 6, achieving a placebo-adjusted mean reduction of 7.5 points (p=0.011, effect size 0.61) and an 18.2-point reduction from baseline. The 20 mg dose also showed statistically significant improvements in additional endpoints, including the Clinical Global Impression of Severity (CGI-S) scale and both the Positive and Negative Symptom Change scores on the Marder Factor.
Dr. Eiry W. Roberts, Chief Medical Officer at Neurocrine Biosciences, commented, “This Phase 2 study achieved our goal of identifying a well-tolerated, once-daily dosing regimen with a compelling benefit-risk profile. We are committed to addressing the significant need for innovative treatments for schizophrenia and are excited to advance NBI-‘568, the first M4 selective agonist, into Phase 3 trials early next year.”
Dr. Maurizio Fava, Psychiatrist-in-Chief at Massachusetts General Hospital of Harvard University, added, “NBI-1117568 showed a meaningful and statistically significant reduction in PANSS scores and was well tolerated, with minimal gastrointestinal effects and no weight gain compared to placebo. As a selective M4 orthosteric agonist, NBI-1117568 could offer a valuable alternative with fewer side effects for patients and caregivers.”
Overall, NBI-‘568 was generally safe and well tolerated across all doses in the Phase 2 trial. Discontinuation rates due to adverse events were comparable between NBI-‘568 and placebo. The most common adverse events included somnolence, dizziness, and headache. Gastrointestinal issues such as nausea and constipation were infrequent and similar to those with placebo. Cardiovascular events were also rare and not clinically significant. NBI-‘568 did not lead to greater weight gain compared to placebo, and there were few reports of extrapyramidal symptoms.
