Neurocrine Biosciences Initiates Phase 3 Registrational Program for NBI-1117568 as Potential Treatment for Adults with Schizophrenia
Neurocrine Biosciences has launched a Phase 3 registrational program to test NBI-1117568, an oral muscarinic M4 selective orthosteric agonist, for treating adults with schizophrenia. This advancement follows successful Phase 2 results from August 2024.
The Phase 3 trial will be a global, double-blind, placebo-controlled study involving approximately 280 adult patients with schizophrenia experiencing acute symptom exacerbation. The study's primary goal is to measure reduction in the Positive and Negative Syndrome Scale (PANSS), with a secondary focus on the Clinical Global Impression of Severity (CGI-S) scale.
Phase 2 results showed promising outcomes with the 20 mg daily dose, including:
- A significant PANSS score reduction of 7.5 points versus placebo
- An 18.2-point reduction from baseline
- Improvements in secondary endpoints
- Good safety profile with minimal side effects
Neurocrine Biosciences ha avviato un programma registrativo di Fase 3 per testare NBI-1117568, un agonista ortosterico orale selettivo del recettore muscarinico M4, destinato al trattamento di adulti con schizofrenia. Questo progresso segue i risultati positivi ottenuti nella Fase 2 ad agosto 2024.
Lo studio di Fase 3 sarà globale, in doppio cieco e controllato con placebo, coinvolgendo circa 280 pazienti adulti con schizofrenia che manifestano un peggioramento acuto dei sintomi. L'obiettivo principale dello studio è la riduzione del punteggio nella Positive and Negative Syndrome Scale (PANSS), con un focus secondario sulla scala Clinical Global Impression of Severity (CGI-S).
I risultati della Fase 2 hanno evidenziato risultati promettenti con la dose giornaliera di 20 mg, tra cui:
- Una significativa riduzione del punteggio PANSS di 7,5 punti rispetto al placebo
- Una riduzione di 18,2 punti rispetto al basale
- Miglioramenti negli endpoint secondari
- Un buon profilo di sicurezza con effetti collaterali minimi
Neurocrine Biosciences ha iniciado un programa de registro de Fase 3 para evaluar NBI-1117568, un agonista ortostérico oral selectivo del receptor muscarínico M4, para el tratamiento de adultos con esquizofrenia. Este avance sigue a los exitosos resultados de la Fase 2 obtenidos en agosto de 2024.
El ensayo de Fase 3 será un estudio global, doble ciego y controlado con placebo, que involucrará aproximadamente a 280 pacientes adultos con esquizofrenia que experimentan un empeoramiento agudo de los síntomas. El objetivo principal del estudio es medir la reducción en la Escala de Síndrome Positivo y Negativo (PANSS), con un enfoque secundario en la Escala de Impresión Clínica Global de Severidad (CGI-S).
Los resultados de la Fase 2 mostraron resultados prometedores con la dosis diaria de 20 mg, incluyendo:
- Una reducción significativa de 7,5 puntos en la puntuación PANSS frente al placebo
- Una reducción de 18,2 puntos desde la línea base
- Mejoras en los puntos finales secundarios
- Buen perfil de seguridad con efectos secundarios mínimos
Neurocrine Biosciences는 성인 조현병 치료를 위해 경구용 무스카린 M4 선택적 정족성 작용제인 NBI-1117568의 임상 3상 등록 프로그램을 시작했습니다. 이 진전은 2024년 8월에 성공적인 2상 결과에 이어 이루어졌습니다.
3상 시험은 전 세계적으로 이중맹검 위약 대조 연구로 약 280명의 성인 조현병 환자가 급성 증상 악화를 겪는 환자를 대상으로 진행됩니다. 연구의 주요 목표는 긍정적 및 부정적 증후군 척도(PANSS)의 감소를 측정하는 것이며, 부차적으로 임상 전반적 심각도 평가(CGI-S) 척도에 중점을 둡니다.
2상 결과는 20mg 일일 투여 용량에서 다음과 같은 유망한 결과를 보였습니다:
- 위약 대비 PANSS 점수 7.5점의 유의미한 감소
- 기저선 대비 18.2점 감소
- 2차 평가변수에서의 개선
- 부작용이 적은 우수한 안전성 프로필
Neurocrine Biosciences a lancé un programme d'enregistrement en Phase 3 pour tester NBI-1117568, un agoniste orthostérique oral sélectif du récepteur muscarinique M4, destiné au traitement des adultes atteints de schizophrénie. Cette avancée fait suite aux résultats positifs de la Phase 2 en août 2024.
L'essai de Phase 3 sera une étude mondiale, en double aveugle, contrôlée par placebo, impliquant environ 280 patients adultes souffrant de schizophrénie et présentant une exacerbation aiguë des symptômes. L'objectif principal de l'étude est de mesurer la réduction sur l'échelle Positive and Negative Syndrome Scale (PANSS), avec un objectif secondaire sur l'échelle Clinical Global Impression of Severity (CGI-S).
Les résultats de la Phase 2 ont montré des résultats prometteurs avec la dose quotidienne de 20 mg, notamment :
- Une réduction significative de 7,5 points sur le score PANSS par rapport au placebo
- Une réduction de 18,2 points par rapport à la valeur initiale
- Des améliorations sur les critères secondaires
- Un bon profil de sécurité avec des effets secondaires minimes
Neurocrine Biosciences hat ein Phase-3-Registrierungsprogramm gestartet, um NBI-1117568, einen oralen muskarinischen M4-selektiven orthosterischen Agonisten, zur Behandlung von Erwachsenen mit Schizophrenie zu testen. Dieser Fortschritt folgt auf erfolgreiche Phase-2-Ergebnisse aus August 2024.
Die Phase-3-Studie wird eine globale, doppelblinde, placebokontrollierte Studie sein, an der etwa 280 erwachsene Patienten mit Schizophrenie teilnehmen, die eine akute Verschlechterung der Symptome erleben. Das Hauptziel der Studie ist die Messung der Reduktion auf der Positive and Negative Syndrome Scale (PANSS), mit einem sekundären Fokus auf die Clinical Global Impression of Severity (CGI-S) Skala.
Die Phase-2-Ergebnisse zeigten vielversprechende Resultate mit der täglichen 20 mg-Dosis, darunter:
- Eine signifikante PANSS-Punktreduktion von 7,5 Punkten gegenüber Placebo
- Eine Reduktion von 18,2 Punkten gegenüber dem Ausgangswert
- Verbesserungen bei sekundären Endpunkten
- Gutes Sicherheitsprofil mit minimalen Nebenwirkungen
- Phase 2 trial met primary endpoint with statistically significant results (p=0.011)
- Strong efficacy data: 18.2-point reduction from baseline in PANSS score
- Drug showed positive safety profile with minimal adverse events
- Successful advancement to Phase 3 trials indicates development progress
- Multiple secondary endpoints met with statistical significance
- Large Phase 3 trial with 280 patients will require significant financial investment
- Still years away from potential market approval and revenue generation
- Faces established competition in crowded schizophrenia treatment market
Insights
Neurocrine's advancement of NBI-1117568 to Phase 3 for schizophrenia, backed by strong Phase 2 data, represents significant pipeline progress with novel mechanism.
Neurocrine's advancement of NBI-1117568 to Phase 3 marks a critical milestone in their development pathway for this schizophrenia treatment candidate. The progression follows positive Phase 2 results that demonstrated statistically significant efficacy with a placebo-adjusted PANSS reduction of 7.5 points (p=0.011) and meaningful effect size of 0.61 for the once-daily 20mg dose.
The clinical significance here is substantial - the PANSS reduction exceeds the typically accepted threshold (5-7 points) for meaningful clinical improvement in schizophrenia studies. This muscarinic M4 selective orthosteric agonist represents a novel mechanism of action distinct from traditional dopamine D2 receptor antagonists that dominate current schizophrenia treatment.
The Phase 3 design involving approximately 280 patients suggests a focused, potentially efficient registration pathway. The favorable safety profile noted in Phase 2 - with minimal gastrointestinal and cardiovascular adverse events - addresses important concerns for antipsychotic medications, which often struggle with tolerability issues.
This program targets schizophrenia, which affects approximately 24 million people worldwide, with many patients experiencing inadequate symptom control or intolerable side effects with current therapies. A successful novel mechanism could address significant unmet medical needs in this devastating psychiatric disorder.
NBIX's Phase 3 initiation represents significant derisking of their CNS pipeline with a differentiated mechanism in the multi-billion dollar schizophrenia market.
Neurocrine's transition to Phase 3 for NBI-1117568 represents significant pipeline advancement for their CNS portfolio. This follows positive Phase 2 efficacy signals with statistical significance (p=0.011) and a robust effect size of 0.61 - parameters that substantially derisk the program moving forward.
The muscarinic M4 selective orthosteric agonist approach is particularly noteworthy as it represents a differentiated mechanism in the antipsychotic landscape. Current treatments predominantly target dopamine pathways, often with considerable side effect profiles that limit adherence and effectiveness.
The trial's design with 280 patients suggests an efficient development approach that could potentially accelerate time-to-market if successful. The clean safety profile in Phase 2 is particularly encouraging, as side effect management remains a critical challenge in schizophrenia treatment compliance.
From a competitive positioning perspective, novel mechanisms with improved tolerability profiles that maintain efficacy can capture significant market share in the antipsychotic space. The schizophrenia market is substantial, with high unmet need for treatments offering better efficacy-to-side-effect profiles. Success in this program would meaningfully expand Neurocrine's commercial portfolio beyond their current products.
"There is a significant need for new and innovative medicines to treat schizophrenia, a disorder that impacts millions of people and their families," said Eiry W. Roberts, M.D., Chief Medical Officer, Neurocrine Biosciences. "With positive Phase 2 data in hand, we're excited to advance this investigational novel compound that works directly and selectively at the muscarinic M4 receptor."
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. The study is expected to enroll approximately 280 patients. The primary endpoint of the study is a reduction from baseline in the Positive and Negative Syndrome Scale (PANSS). The key secondary endpoint is improvement in the Clinical Global Impression of Severity (CGI-S) scale.
Neurocrine is initiating the Phase 3 study supported by positive top-line data from the Phase 2 clinical study, which met its primary endpoint for the once-daily 20 mg dose. The study found:
- A clinically meaningful and statistically significant reduction from baseline in the 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.
- A statistically significant improvement across several secondary endpoints, including the CGI-S scale, Marder Factor Score – Positive Symptom Change, and Marder Factor Score – Negative Symptom Change.
- NBI-1117568 was generally safe and well tolerated at all doses studied, with minimal gastrointestinal and cardiovascular adverse events.
About NBI-1117568
NBI-1117568 is the first and only investigational oral muscarinic M4 selective orthosteric agonist in clinical development for the treatment of schizophrenia. 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-1117568 offers the potential for a novel mechanism with an improved safety profile without the need for combination therapy to minimize off-target pharmacology-related side effects, while also not being dependent on the presence of acetylcholine for efficacy.
About Neurocrine Biosciences' Muscarinic Portfolio
In addition to NBI-1117568, Neurocrine 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. Neurocrine also is developing NBI-1076986, an investigational, selective M4 antagonist that was discovered and is being developed internally at Neurocrine.
Compound | Primary Mechanism | Phase | Therapeutic | Potential Areas for |
NBI-1117568 | M4 agonist | 3 | Psychosis | Alzheimer's Disease |
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 |
About Schizophrenia
Schizophrenia is a serious and complex syndrome with heterogeneous symptoms. The World Health Organization estimates that the disorder impacts approximately 24 million people worldwide. Annual associated costs for schizophrenia are estimated to be more than
About Neurocrine Biosciences, Inc.
Neurocrine Biosciences is a leading neuroscience-focused, biopharmaceutical company with a simple purpose: to relieve suffering for people with great needs. 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, classic congenital adrenal hyperplasia, endometriosis* and uterine fibroids*, as well as a robust pipeline including multiple compounds in mid- to late-phase 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, and Facebook.
(*in collaboration with AbbVie)
NEUROCRINE, the NEUROCRINE BIOSCIENCES Logo, 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. Factors that could cause actual results to differ materially from those stated or implied in the forward-looking statements include, but are not limited to, the following: 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
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