Overview
To date, acalabrutinib has been used in trials studying the treatment of B-All, myelofibrosis, ovarian cancer, multiple myeloma, and Hodgkin lymphoma, among others. As of October 31, 2017 the FDA approved Astra Zeneca's orally administered Calquence (acalabrutinib, capsules). This Bruton tyrosine kinase (BTK) inhibitor indicated for the treatment of chronic lymphocytic leukemia, small lymphocytic lymphoma, and in adult patients with Mantle cell lymphoma (MCL) who have already received at least one prior therapy. In August 2022, the FDA approved a new tablet formulation of Calquence, enabling the co-administration of this drug with proton pump inhibitors (PPIs). Unlike Calquence capsules, the co-administration of Calquence tablets and PPIs does not have an effect in the pharmacokinetics of acalabrutinib. Also known as ACP-196, acalabrutinib is also considered a second generation BTK inhibitor because it was rationally designed to be more potent and selective than ibrutinib, theoretically expected to demonstrate fewer adverse effects owing to minimized bystander effects on targets other than BTK. Nevertheless, acalabrutinib was approved under the FDA's accelerated approval pathway, which is based upon overall response rate and faciliates earlier approval of medicines that treat serious conditions or/and that fill an unmet medical need based on a surrogate endpoint. Continued approval for acalabrutinib's currently accepted indication may subsequently be contingent upon ongoing verification and description of clinical benefit in confimatory trials. Furthermore, the FDA granted this medication Priority Review and Breakthrough Therapy designations. It also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. At this time, more than 35 clinical trials across 40 countries with more than 2500 patients are underway or have been completed with regards to further research into better understanding and expanding the therapeutic uses of acalabrutinib .
Indication
Acalabrutinib is currently indicated for the treatment of adult patients with Mantle Cell Lymphoma (MCL) who have received at least one prior therapy. It has also been recently approved for chronic lymphocytic leukemia and small lymphocytic lymphoma.
Associated Conditions
- Chronic Lymphocytic Leukemia
- Mantle Cell Lymphoma (MCL)
- Small Lymphocytic Lymphoma
Research Report
Acalabrutinib (Calquence): A Comprehensive Monograph on a Second-Generation BTK Inhibitor in Hematologic Malignancies
1.0 Introduction and Overview
Acalabrutinib represents a significant advancement in the targeted therapy of B-cell malignancies, embodying the principles of rational drug design to enhance the therapeutic window of its class. Marketed by AstraZeneca under the brand name Calquence, acalabrutinib is a second-generation, highly selective, and potent irreversible inhibitor of Bruton's tyrosine kinase (BTK).[1] BTK is an indispensable enzyme within the B-cell receptor (BCR) signaling pathway, a cascade that is fundamental to the proliferation, trafficking, and survival of both normal and malignant B-lymphocytes.[4] The clinical validation of BTK as a therapeutic target was firmly established by the first-in-class inhibitor, ibrutinib. However, the clinical utility of ibrutinib, while transformative, was frequently constrained by off-target toxicities stemming from its inhibition of other structurally related kinases, such as those in the TEC and EGFR families.[2] These off-target effects are associated with notable adverse events, including bleeding, atrial fibrillation, severe diarrhea, and skin rash, which can lead to dose reductions or treatment discontinuation.[2]
In this context, acalabrutinib (also known as ACP-196) was deliberately engineered to overcome these limitations. Its molecular structure was optimized for high potency and specificity for BTK, with the explicit goal of minimizing interaction with other kinases to theoretically reduce off-target adverse effects and improve overall tolerability.[1] This design philosophy—improving safety without compromising efficacy—is the central tenet of acalabrutinib's clinical development and its primary differentiator in the therapeutic landscape.
Clinical Trials
Title | Posted | Study ID | Phase | Status | Sponsor |
---|---|---|---|---|---|
2025/07/06 | Not Applicable | Not yet recruiting | Inhye Ahn | ||
2025/06/17 | Phase 2 | Not yet recruiting | |||
2025/06/11 | Phase 2 | Not yet recruiting | Zulfa Omer | ||
2025/02/26 | Phase 2 | Recruiting | Sun Yat-sen University | ||
2025/02/21 | Phase 2 | Withdrawn | |||
2025/01/03 | Phase 2 | Recruiting | |||
2024/10/22 | Phase 4 | Recruiting | |||
2024/08/21 | Phase 1/2 | Recruiting | |||
2024/06/04 | Phase 2 | Not yet recruiting | |||
2024/05/24 | Phase 2/3 | Recruiting |
FDA Drug Approvals
Approved Product | Manufacturer | NDC Code | Route | Strength | Effective Date |
---|---|---|---|---|---|
AstraZeneca Pharmaceuticals LP | 0310-0512 | ORAL | 100 mg in 1 1 | 3/23/2022 | |
AstraZeneca Pharmaceuticals LP | 0310-3512 | ORAL | 100 mg in 1 1 | 8/4/2022 |
EMA Drug Approvals
Approved Product | Authorization Holder | Status | Issued Date |
---|---|---|---|
Authorised | 11/5/2020 | ||
Authorised | 11/5/2020 | ||
Authorised | 11/5/2020 | ||
Authorised | 11/5/2020 |
HSA Drug Approvals
Approved Product | Manufacturer | Approval Number | Dosage Form | Strength | Approval Date |
---|---|---|---|---|---|
CALQUENCE FILM-COATED TABLET 100MG | SIN16875P | TABLET, FILM COATED | 100mg | 9/29/2023 | |
CALQUENCE HARD CAPSULES 100MG | SIN15753P | CAPSULE | 100mg | 7/25/2019 |
NMPA Drug Approvals
Approved Product | Company | Approval Number | Drug Type | Dosage Form | Approval Date |
---|---|---|---|---|---|
No NMPA approvals found for this drug. |
PPB Drug Approvals
Approved Product | Registration No. | Company | Licence No. | Strength | Registration Date |
---|---|---|---|---|---|
No PPB approvals found for this drug. |
TGA Drug Approvals
Approved Product | ARTG ID | Sponsor | Registration Type | Status | Registration Date |
---|---|---|---|---|---|
CALQUENCE acalabrutinib 100 mg capsule blister pack | 321419 | Medicine | A | 11/21/2019 | |
CALQUENCE acalabrutinib (as maleate) 100 mg film-coated tablet blister pack | 377410 | Medicine | A | 10/13/2022 |
Health Canada Drug Approvals
Approved Product | Company | DIN | Dosage Form | Strength | Market Date |
---|---|---|---|---|---|
CALQUENCE | astrazeneca canada inc | 02491788 | Capsule - Oral | 100 MG | 10/2/2019 |
CIMA AEMPS Drug Approvals
Approved Product | Company | Registration Number | Pharmaceutical Form | Prescription Type | Status |
---|---|---|---|---|---|
CALQUENCE 100 MG CAPSULAS DURAS | 1201479002 | CÁPSULA DURA | Diagnóstico Hospitalario | Not Commercialized |
Philippines FDA Drug Approvals
Approved Product | Company | License Number | Dosage Form | Strength | Approval Date |
---|---|---|---|---|---|
No Philippines FDA approvals found for this drug. |
Saudi SFDA Drug Approvals
Approved Product | Company | License Number | Dosage Form | Strength | Approval Date |
---|---|---|---|---|---|
No Saudi SFDA approvals found for this drug. |
Malaysia NPRA Drug Approvals
Approved Product | Company | Registration Number | Dosage Form | Strength | Approval Date |
---|---|---|---|---|---|
No Malaysia NPRA approvals found for this drug. |
UK EMC Drug Information
Medicine Name | MA Holder | MA Number | Pharmaceutical Form | Active Ingredient | Authorization Date |
---|---|---|---|---|---|
No UK EMC drug information found for this drug. |
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