The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:

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

View full prescribing information for Brukinsa. 

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% (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 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%), hemorrhage (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 an 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 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.

For information on the COVID-19 pandemic, see the following resources:

• FDA: Coronavirus Disease 2019 (COVID-19)
• NCI: Coronavirus: What People With Cancer Should Know
• CDC: Coronavirus (COVID-19)

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Please visit the FDA Hematology/Oncology (Cancer) Approvals & Safety Notifications webpage for a list of current and past approvals.