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Ibrutinib

Generic Name
Ibrutinib
Brand Names
Imbruvica
Drug Type
Small Molecule
Chemical Formula
C25H24N6O2
CAS Number
936563-96-1
Unique Ingredient Identifier
1X70OSD4VX

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

Published: Jul 14, 2025

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.

Continue reading the full research report

Clinical Trials

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Title
Posted
Study ID
Phase
Status
Sponsor
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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NMPA Drug Approvals

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Health Canada Drug Approvals

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Philippines FDA Drug Approvals

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UK EMC Drug Information

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