The Food and Drug Administration (FDA) has approved Brukinsa® (zanubrutinib) for the treatment of adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
Zanubrutinib is a small molecule inhibitor of Bruton tyrosine kinase. The approval was based on efficacy and safety data from the phase 3 SEQUOIA (ClinicalTrials.gov Identifier: NCT03336333) and ALPINE (ClinicalTrials.gov Identifier: NCT03734016) studies, which evaluated zanubrutinib in patients with previously untreated CLL/SLL and relapsed or refractory CLL/SLL, respectively.
SEQUOIA included 479 patients who were randomly assigned to receive either zanubrutinib 160mg orally twice daily until disease progression or unacceptable toxicity (n=241), or bendamustine plus rituximab (BR) for 6 cycles (n=238). With an estimated median follow-up of 25 months, results showed median progression-free survival (primary endpoint) was not reached (95% CI, not estimable [NE]-NE) in the zanubrutinib arm and was 33.7 months (95% CI, 28.1-NE) in the BR arm (hazard ratio [HR], 0.42; 95% CI, 0.28-0.63; P <.0001).
Additionally, in a separate nonrandomized cohort of SEQUOIA, the overall response rate (ORR) was reported to be 88% (95% CI, 81-94) among 110 patients with previously untreated CLL/SLL with 17p deletion. At a median follow-up of 25.1 months, the median duration of response (DOR) was not reached.
The ALPINE trial included 652 patients who were randomly assigned to receive either zanubrutinib 160mg orally twice daily (n=327) or ibrutinib 420mg orally once daily (n=325) until disease progression or unacceptable toxicity. Findings showed an ORR (primary endpoint) of 80% (95% CI, 76-85) in the zanubrutinib arm vs 73% (95%, 68-78) in the ibrutinib arm (response rate ratio, 1.10; 95% CI, 1.01-1.20; P =.0264). At a median follow-up of 14.1 months, the median DOR was not reached in either arm.
“We have seen striking data from the Brukinsa development program demonstrating significant and consistent efficacy across CLL patient sub-types, including the high-risk del17p/TP53 mutated population, and regardless of treatment setting,” said Jennifer R. Brown, MD, PhD, Director of the CLL Center of the Division of Hematologic Malignancies at Dana-Farber Cancer Institute and investigator on the SEQUOIA and ALPINE trials. “With extensive follow-up across the CLL development program and the combined results from the SEQUOIA and ALPINE trials, Brukinsa is established as a new standard of care for CLL.”
Across all clinical trials with zanubrutinib, the most common adverse reactions reported were decreased neutrophil count (42%), upper respiratory tract infection (39%), decreased platelet count (34%), hemorrhage (30%), and musculoskeletal pain (30%). Thirteen percent of patients developed second primary malignancies, including non-skin carcinomas. Atrial fibrillation and grade 3 or higher ventricular arrhythmias were reported in 3.7% and 0.2% of patients, respectively.
Brukinsa is also indicated for the treatment of adults with mantle cell lymphoma (MCL) who have received at least 1 prior therapy; Waldenström’s macroglobulinemia; and relapsed or refractory marginal zone lymphoma in patients who have received at least 1 anti-CD20-based regimen.
The product is supplied as 80mg capsules in 120-count bottles.
- FDA approves zanubrutinib for chronic lymphocytic leukemia or small lymphocytic lymphoma. News release. BeiGene USA, Inc. Accessed January 20, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-zanubrutinib-chronic-lymphocytic-leukemia-or-small-lymphocytic-lymphoma.
- Brukinsa® approved in the US for chronic lymphocytic leukemia. News release. BeiGene. Accessed January 20, 2023. https://www.businesswire.com/news/home/20230119005888/en/BRUKINSA%C2%AE-Approved-in-the-U.S.-for-Chronic-Lymphocytic-Leukemia.
- Brukinsa. Package insert. BeiGene USA, Inc; 2022. Accessed January 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/213217s007lbl.pdf.