Neurocrine Biosciences Reports Positive Phase 2 Data for NBI-1117568 in Adults with Schizophrenia
Neurocrine Biosciences (NBIX) reported positive Phase 2 data for NBI-1117568, an oral muscarinic M4 selective agonist for schizophrenia treatment. The once-daily 20 mg dose met the primary endpoint, showing a statistically significant 7.5-point improvement (p=0.011, 0.61 effect size) in the PANSS Total Score compared to placebo at Week 6. It also demonstrated an 18.2-point PANSS Total Score improvement from baseline.
The 20 mg dose met additional endpoints, including improvements in Clinical Global Impression of Severity Scale and Marder Factor Scores. NBI-'568 was generally safe and well-tolerated at all doses studied. The efficacy, safety, and tolerability results support advancement to Phase 3 in early 2025.
Neurocrine Biosciences (NBIX) ha riportato dati positivi di Fase 2 per NBI-1117568, un agonista selettivo orale per il muscarinico M4 per il trattamento della schizofrenia. La dose giornaliera unica di 20 mg ha raggiunto l'endpoint primario, mostrando un miglioramento statisticamente significativo di 7,5 punti (p=0,011, 0,61 dimensione dell'effetto) nel punteggio totale PANSS rispetto al placebo alla Settimana 6. Ha anche dimostrato un miglioramento di 18,2 punti nel punteggio totale PANSS rispetto al basale.
La dose da 20 mg ha soddisfatto ulteriori endpoint, inclusi miglioramenti nella Scala di Impressione Globale Clinica di Gravità e nei punteggi del Fattore Marder. NBI-1117568 è stato generalmente sicuro e ben tollerato in tutte le dosi studiate. I risultati riguardanti l'efficacia, la sicurezza e la tollerabilità supportano il passaggio alla Fase 3 all'inizio del 2025.
Neurocrine Biosciences (NBIX) reportó d datos positivos de Fase 2 para NBI-1117568, un agonista oral selectivo de M4 muscarínico para el tratamiento de la esquizofrenia. La dosis diaria única de 20 mg cumplió con el endpoint primario, mostrando una mejora estadísticamente significativa de 7.5 puntos (p=0.011, tamaño del efecto de 0.61) en la puntuación total de PANSS en comparación con placebo en la semana 6. También demostró una mejora de 18.2 puntos en la puntuación total de PANSS desde la línea base.
La dosis de 20 mg cumplió con endpoints adicionales, incluidos mejoras en la Escala de Impresión Global de Gravedad y en las Puntuaciones del Factor de Marder. NBI-1117568 fue generalmente seguro y bien tolerado en todas las dosis estudiadas. Los resultados de eficacia, seguridad y tolerabilidad apoyan el avance a Fase 3 a principios de 2025.
Neurocrine Biosciences (NBIX)는 2상 시험에서 긍정적인 데이터를 발표했습니다. NBI-1117568은 조현병 치료를 위한 경구용 M4 선택적 콜린제입니다. 하루 20mg 용량이 주요 목표를 달성하여, 6주 차에 위약 대비 PANSS 총점에서 통계적으로 유의미한 7.5점 개선 (p=0.011, 효과 크기 0.61)을 보였습니다. 또한 기준선 대비 18.2점 개선을 나타냈습니다.
20mg 용량은 임상 전반적인 심각도 개선과 마더 지수 점수의 개선을 포함한 추가 목표를 충족했습니다. NBI-1117568은 모든 연구된 용량에서 일반적으로 안전하고 잘 견딜 수 있습니다. 효능, 안전성 및 내약성 결과는 2025년 초 3상으로의 발전을 지지합니다.
Neurocrine Biosciences (NBIX) a rapporté des données positives de Phase 2 pour NBI-1117568, un agoniste oral sélectif du M4 muscarinique pour le traitement de la schizophrénie. La dose quotidienne unique de 20 mg a atteint l'objectif principal, montrant une amélioration statistiquement significative de 7,5 points (p=0,011, taille d'effet de 0,61) dans le score total PANSS par rapport au placebo à la semaine 6. Elle a également démontré une amélioration de 18,2 points du score total PANSS par rapport au point de départ.
La dose de 20 mg a atteint des objectifs supplémentaires, notamment des améliorations dans l'impression globale clinique de gravité et les scores de Marder. NBI-1117568 s'est révélé généralement sûr et bien toléré à toutes les doses étudiées. Les résultats concernant l'efficacité, la sécurité et la tolérabilité soutiennent le passage à la Phase 3 début 2025.
Neurocrine Biosciences (NBIX) berichtete über positive Phase-2-Daten für NBI-1117568, ein oral verabreichter selektiver Agonist für den muskarinischen M4-Rezeptor zur Behandlung von Schizophrenie. Die tägliche Dosis von 20 mg erreichte das primäre Ziel und zeigte eine statistisch signifikante Verbesserung von 7,5 Punkten (p=0,011, Effektgröße 0,61) im PANSS-Gesamtpunktestand im Vergleich zu Placebo in Woche 6. Außerdem wurde eine Verbesserung von 18,2 Punkten im PANSS-Gesamtpunktestand gegenüber dem Ausgangswert nachgewiesen.
Die 20 mg-Dosis erfüllte weitere Endpunkte, einschließlich Verbesserungen in der Skala für die klinische globale Eindrucksschwere und den Marder-Faktoren. NBI-1117568 war allgemein sicher und gut verträglich in allen untersuchten Dosen. Die Ergebnisse zu Wirksamkeit, Sicherheit und Verträglichkeit unterstützen den Fortschritt zu Phase 3 Anfang 2025.
- Phase 2 study met primary endpoint for once-daily 20 mg dose
- Statistically significant 7.5-point improvement in PANSS Total Score vs placebo
- 18.2-point reduction from baseline in PANSS Total Score
- Met additional endpoints including CGI-S and Marder Factor Scores
- Generally safe and well-tolerated at all doses studied
- Advancing to Phase 3 in early 2025
- Minimal GI effects and no weight gain relative to placebo
- Higher doses (40 mg, 60 mg QD, 30 mg BID) did not show statistically significant improvements vs placebo
Insights
The Phase 2 results for NBI-1117568 in schizophrenia are promising. The 20 mg once-daily dose demonstrated a statistically significant 7.5-point improvement in PANSS Total Score compared to placebo, with an impressive effect size of 0.61. This exceeds the typical threshold for clinical significance in schizophrenia trials. The drug also showed improvements in secondary endpoints, including CGI-S and Marder Factor Scores.
Importantly, NBI-'568 exhibited a favorable safety profile with minimal GI effects and no weight gain relative to placebo. These characteristics differentiate it from many existing antipsychotics, potentially offering a competitive advantage. The advancement to Phase 3 in early 2025 suggests confidence in the drug's potential, though investors should note that larger trials are needed to confirm efficacy and safety.
NBI-1117568's mechanism as a selective M4 muscarinic agonist represents an innovative approach in schizophrenia treatment. Unlike traditional dopamine D2 antagonists, M4 agonists may offer antipsychotic efficacy with fewer motor side effects. The positive results across both positive and negative symptoms are particularly noteworthy, as negative symptoms are often challenging to treat.
The drug's once-daily dosing and favorable side effect profile could potentially improve patient adherence, a critical factor in schizophrenia management. However, it's important to monitor long-term effects, especially on cognitive function, as muscarinic agents can impact memory processes. The broader muscarinic portfolio suggests Neurocrine is positioning itself as a leader in this novel therapeutic approach, which could be transformative if successful in late-stage trials.
Neurocrine Biosciences' positive Phase 2 results for NBI-1117568 could significantly impact its market position. The global schizophrenia drug market, valued at
Investors should note that Neurocrine's muscarinic portfolio extends beyond schizophrenia, with potential applications in Alzheimer's, Parkinson's and other neurological disorders. This diversification could mitigate risk and open multiple revenue streams. However, the timeline to potential commercialization (Phase 3 starting in 2025) means significant R&D expenses in the near term. The company's ability to fund these trials and potential partnerships will be important factors to monitor.
- The Once-Daily 20 mg Dose Met the Primary Endpoint, Demonstrating a Statistically Significant 7.5-Point Improvement (p=0.011, 0.61 Effect Size) in the PANSS Total Score Compared to Placebo at Week 6 with an 18.2-Point PANSS Total Score Improvement from Baseline
- The Once-Daily 20 mg Dose Met Additional Endpoints, Demonstrating Statistically Significant Improvements in Clinical Global Impression of Severity Scale and Marder Factor Score Positive Symptom Change and Negative Symptom Change
- NBI-'568 Was Generally Safe and Well Tolerated at All Doses Studied
- The Once-Daily 20 mg Dose Efficacy, Safety and Tolerability Phase 2 Results Support Advancement to Phase 3 in Schizophrenia in Early 2025
- Company to Host Conference Call with Management at 8 a.m. EDT
The NBI-'568-SCZ2028 dose-finding study met its primary endpoint for the once-daily 20 mg dose. It demonstrated 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. The once-daily 20 mg dose also demonstrated a statistically significant improvement for additional endpoints, including improvement in the Clinical Global Impression of Severity (CGI-S) scale, Marder Factor Score – Positive Symptom Change, and Marder Factor Score – Negative Symptom Change.
"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, M.D., 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."
"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 Dr. Maurizio Fava, Psychiatrist-in-Chief at Massachusetts General Hospital of Harvard University. "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."
NBI-'568 was generally safe and well tolerated at all doses studied in the Phase 2 clinical trial. 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 including nausea and constipation were low in frequency and similar to placebo. Cardiovascular-related events were also low in frequency and were not deemed to have clinical relevance at any dose tested. NBI-'568 was not associated with a greater increase in weight than placebo. Few extrapyramidal symptoms adverse events were reported.
Primary Endpoint Results Summary
Week 6 (Day 42) | Placebo (N=68) | 20 mg QD (N=35) | 40 mg QD (N=38) | 60 mg QD (N=34) | 30 mg BID (N=26) |
PANSS Total Score LS Mean Change from Baseline* | -10.8 | -18.2 | -12.6 | -13.7 | -15.8 |
LS Mean Difference vs. Placebo* | - | -7.5 (p=0.011) | -1.9 (p=0.282) | -2.9 (p=0.189) | -5.0 (p=0.090) |
Effect Size** | - | 0.61 | 0.27 | 0.39 | 0.23 |
*Least-squares (LS) means are from a MMRM which includes treatment group, visit, and study period as fixed effects; treatment group-by-visit interaction; baseline PANSS total score as a covariate; and subject as a random effect. | |||||
Next Steps for Neurocrine Biosciences' Muscarinic Portfolio
In addition to NBI-'568, Neurocrine Biosciences has a broad portfolio of assets in clinical development that selectively target muscarinic receptors. The company's muscarinic agonist portfolio also includes NBI-1117567, NBI-1117569, and NBI-1117570, which the company acquired the rights to develop and commercialize from Nxera Pharma (formerly Sosei Heptares). Neurocrine Biosciences is also developing NBI-1076986, a selective M4 antagonist that was discovered and is being developed internally at Neurocrine.
Compound | Primary Mechanism (M1-M4) | Phase | Therapeutic Areas | Potential Areas for Development |
NBI-1117568 | M4 agonist | 2 | Psychosis Cognition | Alzheimer's Disease Bipolar Disorder Lewy Body Dementia Parkinson's Disease Schizophrenia |
NBI-1117567 | M1 agonist | 1 | ||
NBI-1117569 | M4 agonist | 1 | ||
NBI-1117570 | M1/M4 dual agonist | 1 | ||
NBI-1076986 | M4 antagonist | 1 | Movement Disorders | Dystonia Parkinson's Disease Tremor |
Conference Call and Webcast Today at 8:00 AM Eastern Time
Neurocrine Biosciences will hold a live conference call and webcast today at 8:00 a.m. Eastern Time (5:00 a.m. Pacific Time). Participants can access the live conference call by dialing 800-579-2543 (
About NBI-1117568
NBI-'568 is the first and only M4 selective orthosteric agonist in clinical development. There are five muscarinic acetylcholine receptors involved in neurotransmission. Muscarinic receptors are central to brain function and validated as drug targets in psychosis and cognitive disorders. As an M4 selective orthosteric agonist, NBI-'568 offers the potential for a novel mechanism with an improved safety profile without the need of combination therapy to minimize off-target pharmacology-related side effects, while also not being dependent on the presence of acetylcholine for efficacy.
About the NBI-1117568-SCZ2028 Phase 2 Clinical Study
The Phase 2, multicenter, randomized, double-blind, placebo-controlled, multi-arm, multi-stage inpatient dose-finding study was designed to assess the efficacy, safety, tolerability, and pharmacokinetics (PK) of NBI-'568 compared with placebo in adult subjects with a primary diagnosis of schizophrenia who are experiencing an acute exacerbation or relapse of symptoms. The study enrolled 210 participants. For more information about this study, visit ClinicalTrials.gov.
About Schizophrenia
Schizophrenia is a serious and complex syndrome with heterogeneous symptoms. The World Health Organization estimates that the disorder impacts more than 20 million people worldwide. Annual associated costs for schizophrenia are estimated to be more than
About Neurocrine Biosciences
Neurocrine Biosciences is a leading neuroscience-focused, biopharmaceutical company with a simple purpose: to relieve suffering for people with great needs, but few options. We are dedicated to discovering and developing life-changing treatments for patients with under-addressed neurological, neuroendocrine, and neuropsychiatric disorders. The company's diverse portfolio includes FDA-approved treatments for tardive dyskinesia, chorea associated with Huntington's disease, endometriosis* and uterine fibroids*, as well as a robust pipeline including multiple compounds in mid- to late-stage clinical development across our core therapeutic areas. For three decades, we have applied our unique insight into neuroscience and the interconnections between brain and body systems to treat complex conditions. We relentlessly pursue medicines to ease the burden of debilitating diseases and disorders, because you deserve brave science. For more information, visit neurocrine.com, and follow the company on LinkedIn, X (formerly Twitter), and Facebook.
(*in collaboration with AbbVie)
The NEUROCRINE BIOSCIENCES Logo Lockup and YOU DESERVE BRAVE SCIENCE are registered trademarks of Neurocrine Biosciences, Inc.
Forward-Looking Statements
In addition to historical facts, this press release contains forward-looking statements that involve a number of risks and uncertainties. These statements include, but are not limited to, statements regarding the clinical results from, and our future development plans with respect to, NBI-1117568, as well as the therapeutic potential and clinical benefits or safety profile of NBI-1117568. Among the factors that could cause actual results to differ materially from those indicated in the forward-looking statements are: top-line data that we report may change following a more comprehensive review of the data related to the clinical study and such data may not accurately reflect the complete results of the clinical study; risks that clinical development activities may not be initiated or completed on time or at all, or may be delayed for regulatory, manufacturing, or other reasons, may not be successful or replicate previous clinical trial results, may fail to demonstrate that our product candidates are safe and effective, or may not be predictive of real-world results or of results in subsequent clinical trials; risks that regulatory submissions for our product candidates may not occur or be submitted in a timely manner; our future financial and operating performance; risks associated with our dependence on third parties for development, manufacturing, and commercialization activities for our products and product candidates, and our ability to manage these third parties; risks that the FDA or other regulatory authorities may make adverse decisions regarding our products or product candidates; risks that the potential benefits of the agreements with our collaboration partners may never be realized; risks that our products, and/or our product candidates may be precluded from commercialization by the proprietary or regulatory rights of third parties, or have unintended side effects, adverse reactions or incidents of misuse; risks associated with
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FAQ
What were the key results of Neurocrine Biosciences' Phase 2 trial for NBI-1117568 in schizophrenia?
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What side effects were reported in the Phase 2 trial of NBI-1117568 for schizophrenia?
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