FDA Approves Zanubrutinib for Chronic Lymphocytic Leukaemia or Small Lymphocytic Lymphoma

On 19 January 2023, the US Food and Drug Administration (FDA) approved zanubrutinib (Brukinsa, BeiGene USA, Inc.) for chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL).

Full prescribing information for Brukinsa is available here.

Efficacy in patients with treatment-naïve CLL/SLL was evaluated in SEQUOIA (NCT03336333). In the randomised cohort including patients without 17p deletion, a total of 479 patients were randomised 1:1 to receive either zanubrutinib until disease progression or unacceptable toxicity or bendamustine plus rituximab for 6 cycles. The main efficacy outcome measure was progression-free survival (PFS) as determined by an independent review committee (IRC). The median PFS was not reached (95% confidence interval [CI] NE, NE) in the zanubrutinib arm and was 33.7 months (95% CI 28.1, NE) in the bendamustine plus rituximab arm (hazard ratio 0.42, 95% CI 0.28, 0.63; p ≤ 0.0001). Estimated median follow-up for PFS was 25.0 months. In a separate non-randomised cohort of SEQUOIA, zanubrutinib was evaluated in 110 patients with previously untreated CLL/SLL with 17p deletion. Overall response rate (ORR) per IRC was 88% (95% CI 81, 94). The median duration of response (DoR) was not reached after a median follow-up of 25.1 months.

Efficacy in patients with relapsed or refractory CLL/SLL was evaluated in ALPINE (NCT03734016). A total of 652 patients were randomised 1:1 to receive either zanubrutinib or ibrutinib. The median number of prior lines of treatment was 1 (range 1-8). The main efficacy outcome measures at this time of response analysis were ORR and DoR as determined by an IRC. The ORR was 80% (95% CI 76, 85) in the zanubrutinib arm and 73% (95% CI 68, 78) in the ibrutinib arm (response rate ratio 1.10, 95% CI 1.01, 1.20; p = 0.0264). The median DoR was not reached in either arm, after a median follow-up of 14.1 months.

Across clinical trials of zanubrutinib, the most common adverse reactions (≥30%) were neutrophil count decreased (42%), upper respiratory tract infection (39%), platelet count decreased (34%), haemorrhage (30%), and musculoskeletal pain (30%). Second primary malignancies, including non-skin carcinomas, developed in 13% of patients. Atrial fibrillation or flutter were reported in 3.7% of patients, and Grade 3 or higher ventricular arrhythmias in 0.2% of patients.

The recommended zanubrutinib dosage is 160 mg taken orally twice daily or 320 mg taken orally once daily until disease progression or unacceptable toxicity.

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

This application was granted orphan drug designation.

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.

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