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  6. FDA approves zanubrutinib for Waldenström’s macroglobulinemia
  1. Resources for Information | Approved Drugs

FDA approves zanubrutinib for Waldenström’s macroglobulinemia


On August 31, 2021, the Food and Drug Administration approved zanubrutinib (Brukinsa, BeiGene) for adult patients with Waldenström’s macroglobulinemia (WM).

Zanubrutinib was investigated in ASPEN (NCT03053440), a randomized, active control, open-label trial, comparing zanubrutinib and ibrutinib in patients with MYD88 L265P mutation (MYD88MUT) WM. Patients 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 patients with MYD88 wildtype (MYD88WT) or MYD88 mutation unknown WM (n=26 and 2, respectively) and received zanubrutinib 160 mg twice daily.

The major efficacy outcome used to support approval was response rate defined as partial response (PR) or better as assessed by an independent review committee based on standard consensus response criteria from the International Workshop on Waldenström’s Macroglobulinemia-6. An additional efficacy outcome measure was duration of response (DOR).

Approval was based on a non-comparative assessment of response and DOR from the zanubrutinib arms. The response rate (CR+VGPR+PR) was 77.5% (95% CI: 68.1,85.1) in the zanubrutinib arm. Event-free DOR at 12 months was 94.4% (95% CI: 85.8, 97.9) in the zanubrutinib arm. In Cohort 2, response (CR+VGPR+PR) as assessed by IRC was seen in 50% (13 out of 26 response evaluable patients; 95% CI: 29.9, 70.1).

The most common adverse reactions, including laboratory abnormalities, (≥ 20%) reported with zanubrutinib are neutrophil count decreased, upper respiratory tract infection, platelet count decreased, rash, hemorrhage, musculoskeletal pain, hemoglobin decreased, bruising, diarrhea, pneumonia, and cough.

The recommended zanubrutinib dosage is 160 mg orally twice daily or 320 mg orally once daily.

View full prescribing information for Brukinsa.

This review used the Assessment Aid a voluntary submission from the applicant to facilitate the FDA’s assessment.

This application was granted  Fast Track  designation and Orphan Designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

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Follow the Oncology Center of Excellence on Twitter @FDAOncology.



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