Positive Phase 2 Results on NBI-1117568 for Schizophrenia Presented at 2025 ASCP Annual Meeting

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CONFERENCE REPORTER

Neurocrine Biosciences recently shared data from the phase 2 study of NBI-1117568 in adults with schizophrenia, which showed a significant improvement in symptoms and overall severity and highlighted new data on the safety and tolerability of the treatment. NBI-1117568 is the first and only investigational oral muscarinic M4 selective orthosteric agonist in clinical development as a potential treatment for schizophrenia. These results were shared at the American Society of Clinical Psychopharmacology 2025 Annual Meeting in Scottsdale, Arizona.¹

“Traditional treatment approaches for schizophrenia can lead to significant short- and long-term challenges and often result in discontinuation of therapy. Given these challenges, there is a continued need for new, effective and tolerable treatment options," said Eiry W. Roberts, MD, the chief medical officer at Neurocrine Biosciences. "This compound is promising as it is a direct and selective muscarinic M4 receptor agonist, which is believed to be a key regulator of neurotransmitters impacted by schizophrenia, and we look forward to advancing its development in the phase 3 registrational program."

In a 6-week, double-blind, placebo-controlled dose-finding study, 210 adults aged 18 to 55 years with a primary diagnosis of schizophrenia who experience an acute exacerbation or relapse of symptoms were randomized (2:1) to either NBI-1117568 (20 mg, 40 mg, 60 mg once daily; 30 mg twice daily) or placebo. Other antipsychotics were not allowed during the study. Participants were then seen in a 2-week safety follow-up. The primary endpoint was the change in total Positive and Negative Syndrome Scale (PANSS) score from baseline to week 6. The study showed statistically significant improvements in PANSS total score with 20 mg of NBI-1117568 once daily by week 3 and at all subsequent visits through week 6. A statistically significant improvement was also observed by week 2 in the Clinical Global Impression of Severity (CGI-S) scale, with continued improvement seen at all following visits through week 6. For all other doses (40 mg and 60 mg once daily, 30 mg twice daily), mean decreases from baseline at week 6 in PANSS total and CGI-S scale scores were greater with NBI-1117568 than with placebo, but not statistically significant.²

NBI-1117568 was generally safe and well tolerated at all doses. Treatment discontinuation rates due to adverse events were similar between NBI-1117568 and placebo. Adverse events with the highest incidence for NBI-1117568 compared with placebo were somnolence (10.7% vs 2.9%, respectively) and dizziness (9.3% vs 1.4%). Increases in heart rate were transient, attenuated over the course of treatment, and not clinically meaningful. No weight gain was associated with the NBI-1117568 treatment groups relative to placebo.

Building on these positive phase 2 results, investigators recently initiated a phase 3 registrational program to further evaluate the efficacy, safety, and tolerability of NBI-1117568 as a potential treatment for schizophrenia. The phase 3 study is a global double-blind, placebo-controlled trial evaluating NBI-1117568 in adults with a primary diagnosis of schizophrenia who are experiencing an acute exacerbation or relapse of symptoms. Investigators expect to enroll approximately 280 patients. The study’s primary endpoint is a reduction from baseline in the PANSS, with a key secondary endpoint being improvement in the CGI-S scale.

References

1. Neurocrine Biosciences presents new positive data from phase 2 study of NBI-1117568 in adults with schizophrenia at American Society of Clinical Psychopharmacology 2025. News release. May 28, 2025. Accessed May 29, 2025. https://www.prnewswire.com/news-releases/neurocrine-biosciences-presents-new-positive-data-from-phase-2-study-of-nbi-1117568-in-adults-with-schizophrenia-at-american-society-of-clinical-psychopharmacology-2025-302467554.html

2. Kuntz L. New positive results for NBI-1117568 in adults with schizophrenia. Psychiatric Times. August 28, 2024. https://www.psychiatrictimes.com/view/new-positive-results-for-nbi-1117568-in-adults-with-schizophrenia