On August 31, the U.S. Food and Drug Administration (FDA) approved zanubrutinib (Brukinsa), a Bruton’s tyrosine kinase inhibitor, for adult patients with Waldenström’s macroglobulinemia.
Zanubrutinib was investigated in ASPEN (ClinicalTrials.gov identifier: NCT03053440), a randomized, active control, open-label trial comparing zanubrutinib and ibrutinib in patients with MYD88 L265P–mutated Waldenström’s macroglobulinemia. Patients in cohort 1 (n = 201) were randomly assigned 1:1 to receive zanubrutinib at 160 mg twice daily or ibrutinib at 420 mg once daily until disease progression or unacceptable toxicity. Cohort 2 enrolled patients with MYD88 wild-type or MYD88 mutation unknown Waldenström’s macroglobulinemia (n = 26 and n = 2, respectively); they received zanubrutinib at 160 mg twice daily.
The major efficacy outcome used to support approval was response rate defined as partial response 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.
Approval was based on a noncomparative assessment of response and duration of response from the zanubrutinib arms. The response rate (complete response + very good partial response + partial response) was 77.5% (95% confidence interval [CI] = 68.1%–85.1%) in the zanubrutinib arm. Event-free duration of response at 12 months was 94.4% (95% CI = 85.8%–97.9%) in the zanubrutinib arm. In Cohort 2, response as assessed by Independent Review Committee was seen in 50% (13 out of 26 response-evaluable patients; 95% CI = 29.9%–70.1%).
The most common adverse reactions (≥ 20%) including laboratory abnormalities reported with zanubrutinib were decreased neutrophil count, upper respiratory tract infection, decreased platelet count, rash, hemorrhage, musculoskeletal pain, decreased hemoglobin, bruising, diarrhea, pneumonia, and cough.
The recommended zanubrutinib dosage is 160 mg orally twice daily or 320 mg orally once daily.
This application was granted Fast Track designation and Orphan designation.