AbbVie Provides Update on Phase 2 Results for Emraclidine in Schizophrenia
AbbVie (NYSE: ABBV) announced that its Phase 2 EMPOWER trials for emraclidine, investigating its use as a once-daily oral treatment for schizophrenia, did not meet their primary endpoint. The trials failed to demonstrate statistically significant reduction in PANSS total scores compared to placebo at week 6. Despite the disappointing results, the drug was well-tolerated with a safety profile similar to Phase 1b trials. Common adverse events included headache (9.4-14.6%), dry mouth (0.8-9.3%), and dyspepsia (1.5-7.8%). The company continues to analyze data to determine next steps while maintaining its commitment to developing treatments for psychiatric and neurological disorders.
AbbVie (NYSE: ABBV) ha annunciato che i suoi trial EMPOWER di Fase 2 per l'emraclidina, che ne indagano l'uso come trattamento orale una volta al giorno per la schizofrenia, non hanno raggiunto il loro obiettivo primario. Gli studi non hanno dimostrato una riduzione statisticamente significativa nei punteggi totali del PANSS rispetto al placebo alla settimana 6. Nonostante i risultati deludenti, il farmaco è stato ben tollerato con un profilo di sicurezza simile a quello dei trial di Fase 1b. Gli eventi avversi comuni includevano mal di testa (9.4-14.6%), bocca secca (0.8-9.3%) e dispepsia (1.5-7.8%). L'azienda continua ad analizzare i dati per determinare i prossimi passi, mantenendo il proprio impegno nello sviluppo di trattamenti per disturbi psichiatrici e neurologici.
AbbVie (NYSE: ABBV) anunció que sus ensayos de Fase 2 EMPOWER para emraclidina, que investigan su uso como tratamiento oral diario para la esquizofrenia, no lograron cumplir con su objetivo primario. Los ensayos no demostraron una reducción estadísticamente significativa en los puntajes totales de PANSS en comparación con el placebo a la semana 6. A pesar de los resultados decepcionantes, el fármaco fue bien tolerado, con un perfil de seguridad similar al de los ensayos de Fase 1b. Los eventos adversos comunes incluyeron dolor de cabeza (9.4-14.6%), boca seca (0.8-9.3%) y dispepsia (1.5-7.8%). La empresa sigue analizando los datos para determinar los próximos pasos, manteniendo su compromiso con el desarrollo de tratamientos para trastornos psiquiátricos y neurológicos.
AbbVie (NYSE: ABBV)는 응용시킨 EMPOWER 2상 임상시험에서 emraclidine이 하루 한 번 복용하는 Schizophrenia 치료제로서의 사용을 조사한 결과 주요 목표를 달성하지 못했다고 발표했습니다. 임상시험은 6주차에 위약과 비교하여 PANSS 총 점수에서 통계적으로 유의미한 감소를 입증하지 못했습니다. 실망스러운 결과에도 불구하고 이 약물은 잘 견딜 수 있었으며 1b상 시험과 유사한 안전성 프로파일을 보였습니다. 흔한 이상 반응으로는 두통 (9.4-14.6%), 입마름 (0.8-9.3%) 및 소화불량 (1.5-7.8%)이 포함되었습니다. 이 회사는 정신과 및 신경질환 치료법 개발에 대한 약속을 유지하며 다음 단계를 결정하기 위해 데이터를 계속 분석하고 있습니다.
AbbVie (NYSE: ABBV) a annoncé que ses essais de phase 2 EMPOWER pour l'emraclidine, étudiant son utilisation en tant que traitement oral quotidien pour la schizophrénie, n'ont pas atteint leur objectif principal. Les essais n'ont pas réussi à démontrer une réduction statistiquement significative des scores totaux du PANSS par rapport au placebo à la semaine 6. Malgré ces résultats décevants, le médicament a été bien toléré avec un profil de sécurité similaire aux essais de phase 1b. Les événements indésirables courants comprenaient des maux de tête (9,4-14,6%), une sécheresse buccale (0,8-9,3%) et une dyspepsie (1,5-7,8%). L'entreprise continue d'analyser les données pour déterminer les prochaines étapes tout en maintenant son engagement à développer des traitements pour les troubles psychiatriques et neurologiques.
AbbVie (NYSE: ABBV) gab bekannt, dass die EMPOWER-Studien der Phase 2 für Emraclidine, die dessen Einsatz als einmal täglich orale Behandlung für Schizophrenie untersuchen, ihr primäres Ziel nicht erreicht haben. Die Studien konnten keinen statistisch signifikanten Rückgang der PANSS-Gesamtwerte im Vergleich zur Placebo-Gruppe in Woche 6 nachweisen. Trotz der enttäuschenden Ergebnisse wurde das Medikament gut vertragen und wies ein Sicherheitsprofil ähnlich den Phase-1b-Studien auf. Häufige unerwünschte Ereignisse waren Kopfschmerzen (9,4-14,6%), Mundtrockenheit (0,8-9,3%) und Dyspepsie (1,5-7,8%). Das Unternehmen analysiert weiterhin die Daten, um die nächsten Schritte zu bestimmen, während es sich verpflichtet, Behandlungen für psychische und neurologische Erkrankungen zu entwickeln.
- Drug demonstrated good tolerability with safety profile consistent with Phase 1b trials
- Company maintains diverse neuroscience pipeline through Cerevel acquisition
- Failed to meet primary endpoint in both EMPOWER-1 and EMPOWER-2 Phase 2 trials
- No statistically significant improvement in PANSS scores versus placebo
- Development setback in key therapeutic area
Insights
The Phase 2 trial results for emraclidine represent a significant setback in AbbVie's neuroscience pipeline. The drug failed to demonstrate statistically significant improvements in PANSS scores compared to placebo, which is important for schizophrenia treatments. While the safety profile appears favorable, with manageable side effects like headache (
The data shows minimal differentiation between treatment groups, with placebo responses of -13.5 to -16.1 points versus emraclidine's -14.2 to -18.5 point improvements. This narrow therapeutic window suggests clinical benefit. This outcome may impact AbbVie's broader neuroscience strategy, particularly following the Cerevel acquisition. However, the company's diversified pipeline and strong market position in psychiatry provide some cushioning against this clinical disappointment.
This clinical trial failure will likely have a moderate negative impact on AbbVie's near-term prospects in the neuroscience space. While the company's
However, AbbVie's strong position in psychiatry with established products and multiple pipeline candidates helps mitigate the impact. The company's commitment to neuroscience development remains supported by substantial resources and commercial infrastructure. Investors should monitor upcoming catalysts from other pipeline assets to better assess the long-term impact on AbbVie's neuroscience ambitions.
- EMPOWER-1 and EMPOWER-2 Phase 2 clinical trials did not meet their primary endpoint
- Emraclidine was well-tolerated with an adverse event profile consistent with Phase 1b trial
"While we are disappointed with the results, we are continuing to analyze the data to determine next steps," said Roopal Thakkar, M.D., executive vice president, research and development, chief scientific officer, AbbVie. "We would like to extend our gratitude to the study participants and their loved ones as well as to our network of clinical investigative sites for their participation in these trials. We are confident that our innovative pipeline will continue to bring meaningful therapies to patients, and we remain committed to finding better treatments for people living with psychiatric and neurological disorders."
Change from Baseline to Week 6 in PANSS Total Score
EMPOWER-1 | EMPOWER-2 | |||||
Placebo (N= 127) | Emraclidine (N = 125) | Emraclidine (N = 127) | Placebo (N = 128) | Emraclidine (N = 122) | Emraclidine (N = 123) | |
Baseline (SD) | 98.3 (8.16) | 97.6 (7.65) | 97.9 (7.89) | 97.4 (8.22) | 98.0 (8.49) | 97.2 (7.75) |
LS Mean ( | -13.5 (-17.0, -10.0) | -14.7 (-18.1, -11.2) | -16.5 (-20.0, -13.1) | -16.1 (-19.4, -12.8) | -18.5 (-22.0, -15.0) | -14.2 (-17.6, -10.8) |
In the EMPOWER trials, emraclidine was well-tolerated with a safety profile comparable to that observed in the Phase 1b trial. The most commonly reported adverse events in EMPOWER-1 and EMPOWER-2, respectively, were headache (
Neuroscience is a key area of focus for AbbVie. In addition to emraclidine, through the Cerevel acquisition AbbVie gained a neuroscience pipeline of multiple clinical-stage and preclinical candidates that are complementary to the company's existing neuroscience portfolio with leading on-market brands in psychiatry, migraine, and Parkinson's disease.
About Schizophrenia
Schizophrenia is a serious, complex, and debilitating mental health disorder characterized by a constellation of symptoms, including delusions, hallucinations, disorganized speech or behavior, slowed speech and blunted affect. Schizophrenia is also often associated with significant cognitive impairment, which further limits a patient's ability to be gainfully employed and maintain relationships. Diagnosis of schizophrenia is usually made in young adulthood and the disease follows a chronic and indolent course characterized by periods of remission and relapse.1 Only
About Emraclidine
Emraclidine is a potential novel M4-selective positive allosteric modulator (PAM) in development for schizophrenia and Alzheimer's disease psychosis as a once-daily medication without the need for titration.7
As a highly selective PAM of centrally located M4 muscarinic acetylcholine receptors, emraclidine is designed to potentially reduce excess dopamine signaling in the striatum without blocking dopamine type 2 (D2) receptors. It is hypothesized that by selectively targeting M4 receptors, emraclidine has the potential to reduce psychotic symptoms without interfering with dopamine, serotonin and/or histamine receptors, which is believed to underlie many of the side effects of current antipsychotics.7
EMPOWER Clinical Development Program
The EMPOWER clinical development program evaluated emraclidine in patients with schizophrenia who are experiencing an acute exacerbation in two adequately-powered, placebo-controlled Phase 2 trials, known as EMPOWER-1 (NCT05227690) and EMPOWER-2 (NCT05227703). The Phase 2 program was designed to study multiple dosing options to enable the full exploration of the therapeutic dose range for emraclidine.
The program also includes a 52-week open label extension trial EMPOWER-3 (NCT05443724) evaluating emraclidine in people living with schizophrenia who have stable symptoms and are not currently experiencing an acute exacerbation of psychotic symptoms.
More information on the EMPOWER trials can be found on www.clinicaltrials.gov.
About AbbVie in Neuroscience
At AbbVie, our commitment to preserving personhood of people around the world living with neurological and psychiatric disorders is unwavering. With more than three decades of experience in neuroscience, we are providing meaningful treatment options today and advancing innovation for the future. AbbVie's Neuroscience portfolio consists of approved treatments in neurological conditions, including migraine, movement disorders and psychiatric disorders, along with a robust pipeline of transformative therapies. We have made a strong investment in research and are committed to building a deeper understanding of neurological and psychiatric disorders. Every challenge makes us more determined and drives us to discover and deliver advancements for those impacted by these conditions, their care partners and clinicians. For more information, visit www.abbvie.com.
About AbbVie
AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas – immunology, oncology, neuroscience, and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on LinkedIn, Facebook, Instagram, X (formerly Twitter), and YouTube.
Forward-Looking Statements
Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions and uses of future or conditional verbs, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2023 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation, and specifically declines, to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.
References
- Patel KR, Cherian J, Gohil K, Atkinson D. Schizophrenia: overview and treatment options. P T. 2014 Sep;39(9):638-45. PMID: 25210417; PMCID: PMC4159061.
- Higashi K, Medic G, Littlewood KJ, Diez T, Granström O, De Hert M. Medication adherence in schizophrenia: factors influencing adherence and consequences of nonadherence, a systematic literature review. Ther Adv Psychopharmacol. 2013 Aug;3(4):200-18. doi: 10.1177/2045125312474019. PMID: 24167693; PMCID: PMC3805432.
- Zipursky RB, Menezes NM, Streiner DL. Risk of symptom recurrence with medication discontinuation in first-episode psychosis: a systematic review. Schizophr Res. 2014 Feb;152(2-3):408-14. doi: 10.1016/j.schres.2013.08.001. Epub 2013 Aug 21. PMID: 23972821.
- Tanskanen A, Tiihonen J, Taipale H. Mortality in schizophrenia: 30-year nationwide follow-up study. Acta Psychiatr Scand. 2018 Dec;138(6):492-499. doi: 10.1111/acps.12913. Epub 2018 Jun 13. PMID: 29900527.
- Crump C, Winkleby MA, Sundquist K, Sundquist J. Comorbidities and mortality in persons with schizophrenia: a Swedish national cohort study. Am J Psychiatry. 2013 Mar;170(3):324-33. doi: 10.1176/appi.ajp.2012.12050599. PMID: 23318474.
- World Health Organization. Schizophrenia. https://www.who.int/news-room/fact-sheets/detail/schizophrenia. Updated January 10, 2022. Accessed March 31, 2022.
- Krystal, John H, et al. Emraclidine, a novel positive allosteric modulator of cholinergic M4 receptors, for the treatment of schizophrenia: a two-part, randomised, double-blind, placebo-controlled, phase 1b trial. The Lancet. 2022; 400(10369): 2210 – 2220. doi: 10.1016/S0140-6736(22)01990-0.
View original content:https://www.prnewswire.com/news-releases/abbvie-provides-update-on-phase-2-results-for-emraclidine-in-schizophrenia-302301190.html
SOURCE AbbVie
FAQ
What were the results of AbbVie's (ABBV) Phase 2 EMPOWER trials for emraclidine?
What were the main side effects reported in AbbVie's (ABBV) emraclidine trials?
What is AbbVie's (ABBV) next step following the emraclidine trial results?
