Overview
Ibrutinib is a small molecule that acts as an irreversible potent inhibitor of Burton's tyrosine kinase. It is designated as a targeted covalent drug and presented as a promising activity in B-cell malignancies in clinical trials. Ibrutinib was developed by Pharmacyclics Inc and was first approved by the FDA in November 2013 for the treatment of mantle cell lymphoma (MCL) under accelerated approval; however, in April 2023, the drug manufacturer withdrew the accelerated approvals for ibrutinib in the US. Ibrutinib was approved by the EMA in October 2014 and by Health Canada in November 2014. It is currently approved for the treatment of various conditions, such as chronic lymphocytic leukemia (CLL), Waldenström's Macroglobulinemia, and chronic graft versus host disease (cGVHD) in August 2017. Notably, ibrutinib became the first FDA-approved cGVHD treatment for children in August 2017.
Indication
Ibrutinib is indicated for the treatment of the following conditions. Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) Waldenström's macroglobulinemia Chronic graft-versus-host disease (cGVHD) Mantle cell lymphoma (MCL) Marginal zone lymphoma (MZL)
Associated Conditions
- Chronic Graft-Versus-Host Disease
- Chronic Lymphocytic Leukemia
- Marginal Zone Lymphoma (MZL)
- Refractory Mantle Cell Lymphoma
- Relapsed Mantle Cell Lymphoma
- Small Lymphocytic Lymphoma
- Steroid-dependent chronic graft-versus-host disease
- Waldenström's Macroglobulinemia (WM)
- Steroid refractory Chronic graft versus host disease
Research Report
Ibrutinib (Imbruvica®): A Comprehensive Clinical Monograph on the First-in-Class BTK Inhibitor
Executive Summary
Ibrutinib (Imbruvica®) is a first-in-class, orally administered small molecule that has fundamentally transformed the therapeutic landscape for B-cell malignancies. As a potent and irreversible inhibitor of Bruton's tyrosine kinase (BTK), Ibrutinib targets a critical enzyme in the B-cell receptor (BCR) signaling pathway, which is frequently dysregulated and constitutively active in cancers such as chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and Waldenström's macroglobulinemia (WM). The mechanism of action involves the formation of a covalent bond with a cysteine residue (Cys481) in the BTK active site, leading to sustained inhibition of kinase activity. This blockade disrupts downstream pro-survival signals, ultimately inducing apoptosis in malignant B-cells and inhibiting their proliferation and trafficking to protective microenvironments.
The clinical development of Ibrutinib is anchored by a robust body of evidence from pivotal clinical trials, most notably the RESONATE and RESONATE-2 studies in CLL. These trials demonstrated unprecedented and durable efficacy, establishing Ibrutinib as a superior treatment option to traditional chemoimmunotherapy, particularly in the first-line setting for older patients and in those with high-risk genomic features. The long-term follow-up from the RESONATE-2 trial, extending up to a decade, has shown a median progression-free survival of nearly nine years and an overall survival rate that approaches that of an age-matched general population, underscoring the profound and lasting benefit of continuous therapy. Ibrutinib has also secured landmark approvals for other B-cell cancers and was the first therapy ever approved by the U.S. Food and Drug Administration (FDA) for the treatment of chronic graft-versus-host disease (cGVHD) in both adult and pediatric populations.
Clinical Trials
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Title | Posted | Study ID | Phase | Status | Sponsor |
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2021/03/17 | Phase 2 | Recruiting | The Lymphoma Academic Research Organisation | ||
2021/03/04 | Phase 1 | Withdrawn | |||
2021/02/25 | Phase 1 | Recruiting | Jeanette Lundin | ||
2021/02/17 | Phase 2 | Recruiting | Paolo Ghia | ||
2021/02/15 | Phase 2 | Active, not recruiting | Paolo Ghia | ||
2021/02/05 | Phase 1 | Recruiting | |||
2020/12/28 | Phase 2 | Withdrawn | Inhye Ahn | ||
2020/12/11 | Phase 2 | Withdrawn | Academic and Community Cancer Research United | ||
2020/12/10 | Phase 3 | Active, not recruiting | |||
2020/10/29 | Phase 1 | Suspended |
FDA Drug Approvals
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EMA Drug Approvals
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HSA Drug Approvals
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NMPA Drug Approvals
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PPB Drug Approvals
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TGA Drug Approvals
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Health Canada Drug Approvals
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CIMA AEMPS Drug Approvals
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Philippines FDA Drug Approvals
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Saudi SFDA Drug Approvals
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Malaysia NPRA Drug Approvals
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UK EMC Drug Information
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