Neurocrine Biosciences Announces Positive Phase 2 Results for NBI-1117568 in Schizophrenia Adults

Neurocrine Biosciences, Inc. has announced encouraging top-line results from its Phase 2 clinical trial of NBI-1117568 (NBI-'568) in adults with schizophrenia. NBI-'568 is the first investigational oral drug that selectively targets the muscarinic M4 receptor for treating schizophrenia.

In a study labeled NBI-'568-SCZ2028, the once-daily 20 mg dose of NBI-'568 achieved its primary endpoint. It demonstrated a significant improvement in the Positive and Negative Syndrome Scale (PANSS) total score at Week 6. Specifically, there was a 7.5-point placebo-adjusted reduction in PANSS total score (p=0.011, effect size of 0.61), translating to an 18.2-point reduction from baseline. Additionally, the 20 mg dose showed significant improvements in other key measures, such as the Clinical Global Impression of Severity (CGI-S) scale, and the Marder Factor Scores for both positive and negative symptom changes.

Dr. Eiry W. Roberts, Chief Medical Officer at Neurocrine Biosciences, expressed satisfaction with the Phase 2 study outcomes, emphasizing the identification of a well-tolerated, once-daily dosing regimen with a favorable benefit-risk profile. Dr. Roberts underscored the urgent need for innovative schizophrenia treatments and announced plans to advance NBI-'568 to Phase 3 development in early 2025.

Dr. Maurizio Fava, Psychiatrist-in-Chief at Massachusetts General Hospital, highlighted the clinical significance of the results. According to Dr. Fava, NBI-'568 could offer an alternative to current schizophrenia treatments, given its efficacy and minimal side effects, including no significant weight gain or gastrointestinal issues compared to placebo.

In terms of safety and tolerability, NBI-'568 performed well across all doses tested in the Phase 2 trial. Discontinuation rates due to adverse events were comparable between the drug and placebo groups. The most common adverse events included somnolence, dizziness, and headache, while gastrointestinal issues like nausea and constipation were infrequent and similar to placebo. Cardiovascular-related adverse events were also uncommon and lacked clinical relevance. Interestingly, NBI-'568 did not lead to significant weight gain, and only a few cases of extrapyramidal symptoms were reported.

Neurocrine Biosciences' muscarinic receptor-targeting portfolio includes several assets, such as NBI-1117567, NBI-1117569, and NBI-1117570, which the company acquired from Nxera Pharma. Additionally, the company is developing NBI-1076986, a selective M4 antagonist developed internally.

NBI-'568 is unique as the only M4 selective orthosteric agonist in clinical development. Muscarinic acetylcholine receptors play a crucial role in brain function and are validated targets for treating psychosis and cognitive disorders. The selectivity of NBI-'568 offers the potential for a novel mechanism with an improved safety profile, without the need for combination therapy to mitigate off-target effects.

The Phase 2 study was a multicenter, randomized, double-blind, placebo-controlled trial involving 210 participants. It aimed to assess the efficacy, safety, tolerability, and pharmacokinetics of NBI-'568 in adults diagnosed with schizophrenia experiencing an acute exacerbation or relapse of symptoms.

Schizophrenia is a complex and debilitating mental health disorder affecting over 20 million people globally. It is characterized by a range of symptoms and poses significant emotional and functional burdens on patients and their families. Traditional antipsychotic treatments often come with substantial side effects, underscoring the need for new medications like NBI-'568.

Neurocrine Biosciences is dedicated to developing treatments for neurological, neuroendocrine, and neuropsychiatric disorders. The company's portfolio includes FDA-approved treatments for various conditions and a pipeline of compounds in mid-to-late-stage clinical development. For three decades, Neurocrine has been pioneering in neuroscience, striving to alleviate the suffering associated with debilitating diseases.