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FDA Actions & Updates

The latest approvals, designations, and new indications from the U.S. Food and Drug Administration for oncology drugs.

Monday, January 23, 2023

Approval of Zanubrutinib for Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

On January 19, 2023, the FDA approved zanubrutinib for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Efficacy in patients with treatment-naïve CLL/SLL was evaluated in SEQUOIA (NCT03336333).

In the randomized cohort including patients without 17p deletion, a total of 479 patients were randomized 1:1 to receive either zanubrutinib until disease progression or unacceptable toxicity or bendamustine plus rituximab (BR) 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% CI: NE, NE) in the zanubrutinib arm and was 33.7 months (95% CI: 28.1, NE) in the BR arm (HR= 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-randomized 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 percent (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 randomized 1:1 to receive either zanubrutinib or ibrutinib. The median number of prior lines of therapy was one (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 percent (95% CI: 76, 85) in the zanubrutinib arm and 73 percent (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%), hemorrhage (30%), and musculoskeletal pain (30%). Second primary malignancies, including non-skin carcinomas, developed in 13 percent of patients. Atrial fibrillation or flutter was reported in 3.7 percent of patients, and Grade 3 or higher ventricular arrhythmias in 0.2 percent 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.​