Zanubrutinib, sold under the brand name Brukinsa, is a

medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...

used for the treatment of

mantle cell lymphoma Mantle cell lymphoma (MCL) is a type of non-Hodgkin's lymphoma (NHL), comprising about 6% of NHL cases. There are only about 15,000 patients presently in the United States with mantle cell lymphoma. It is named for the mantle zone of the lymph n ...

(MCL), Waldenström's macroglobulinemia (WM),

marginal zone lymphoma Marginal zone B-cell lymphomas, also known as marginal zone lymphomas (MZLs), are a heterogeneous group of lymphomas that derive from the malignant transformation of marginal zone B-cells. Marginal zone B cells are innate lymphoid cells that norma ...

(MZL), and

chronic lymphocytic leukemia Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). Early on, there are typically no symptoms. Later, non-painful lymph node swelling, feeling tired, fever, nigh ...

(CLL). Zanubrutinib is classified as a

Bruton's tyrosine kinase Bruton's tyrosine kinase (abbreviated Btk or BTK), also known as tyrosine-protein kinase BTK, is a tyrosine kinase that is encoded by the ''BTK'' gene in humans. BTK plays a crucial role in B cell development. Structure BTK contains five differ ...

(BTK) inhibitor. It is given

by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

. It was approved for medical use in the United States in November 2019.

Medical uses

Zanubrutinib is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

for the treatment of adults with

(MCL) who have received at least one prior therapy, and for the treatment of Waldenström's macroglobulinemia. It is also indicated for the treatment of adults with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen.

History

Efficacy was evaluated in BGB-3111-206 (NCT03206970), a phase II open-label, multicenter, single-arm trial of 86 participants with mantle cell lymphoma (MCL) who received at least one prior therapy. Zanubrutinib was given orally at 160 mg twice daily until disease progression or unacceptable toxicity. Efficacy was also assessed in BGB-3111-AU-003 (NCT02343120), a phase I/II, open-label, dose-escalation, global, multicenter, single-arm trial of B‑cell malignancies, including 32 previously treated MCL participants treated with zanubrutinib administered orally at 160 mg twice daily or 320 mg once daily. The primary efficacy outcome measure in both trials was overall response rate (ORR), as assessed by an independent review committee. In trial BGB-3111-206, FDG-PET scans were required and the ORR was 84% (95% CI: 74, 91), with a complete response rate of 59% (95% CI 48, 70) and a median response duration of 19.5 months (95% CI: 16.6, not estimable). In trial BGB-3111-AU-003, FDG-PET scans were not required and the ORR was 84% (95% CI: 67, 95), with a complete response rate of 22% (95% CI: 9, 40) and a median response duration of 18.5 months (95% CI: 12.6, not estimable). Trial 1 was conducted at 13 sites in China, and Trial 2 was conducted at 25 sites in the United States, United Kingdom, Australia, New Zealand, Italy, and South Korea. The U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) granted zanubrutinib

priority review Priority review is a program of the United States Food and Drug Administration (FDA) to expedite the review process for drugs that are expected to have a particularly great impact on the treatment of a disease. The priority review voucher program ...

accelerated approval The United States Food and Drug Administration (FDA) initiated the FDA Accelerated Approval Program in 1992 to allow faster approval of drugs for serious conditions that fill an unmet medical need. The faster approval relies on use of surrogate endp ...

breakthrough therapy Breakthrough therapy is a United States Food and Drug Administration designation that expedites drug development that was created by Congress under Section 902 of the 9 July 2012 Food and Drug Administration Safety and Innovation Act. The FDA's "br ...

designation, and

orphan drug An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of ...

designation. The FDA approved zanubrutinib in November 2019, and granted the application for Brukinsa to BeiGene USA Inc. In August 2021, the FDA approved zanubrutinib for the treatment of Waldenström's macroglobulinemia and in September 2021, for marginal zone lymphoma (MZL). Zanubrutinib was investigated in ASPEN (NCT03053440), a randomized, active control, open-label trial, comparing zanubrutinib and ibrutinib in participants with MYD88 L265P mutation (MYD88MUT) WM. Participants in Cohort 1 (n=201) were randomized 1:1 to receive zanubrutinib 160 mg twice daily or ibrutinib 420 mg once daily until disease progression or unacceptable toxicity. Cohort 2 enrolled participants with MYD88 wildtype (MYD88WT) or MYD88 mutation unknown WM (n=26 and 2, respectively) and received zanubrutinib 160 mg twice daily. Approval of zanubrutinib for marginal zone lymphoma is based on two open-label, multicenter, single-arm trials: BGB-3111-214 (NCT03846427), which evaluated 66 participants with MZL who received at least one prior anti-CD20-based therapy, and BGB-3111-AU-003 (NCT02343120), which included 20 participants with previously treated MZL.

Society and culture

Legal status

On 16 September 2021, the

Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regarding ...

(CHMP) of the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

(EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Brukinsa, intended for the treatment of Waldenström's macroglobulinaemia (WM). Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged. The applicant for this medicinal product is BeiGene Ireland Ltd. Zanubrutinib was approved for medical use in the European Union in November 2021.

References

External links

* * * * * * * * {{Portal bar , Medicine Breakthrough therapy Carboxamides CYP3A4 inducers Diphenyl ethers Kinase inhibitors Orphan drugs Piperidines Vinyl compounds