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

Zanubrutinib was investigated in ASPEN (NCT03053440), a randomised, active control, open-label trial, comparing zanubrutinib and ibrutinib in patients with MYD88 L265P mutation (MYD88MUT) WM. Patients in Cohort 1 (n=201) were randomised 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, haemorrhage, musculoskeletal pain, haemoglobin decreased, bruising, diarrhoea, pneumonia, and cough.

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

View full prescribing information here.

Source: FDA