Brukinsa demonstrated superior progression-free survival over Imbruvica in chronic lymphocytic leukemia in late-breaker at ASH

These data will be presented (Abstract #LBA-6) during the late-breaking session at the 64th American Society of Hematology (ASH) Annual Meeting in New Orleans and simultaneously published in The New England Journal of Medicine. The paper’s lead author Jennifer Brown, M.D., Ph.D., Director, CLL Center at Dana-Farber Cancer Institute will present these data.

Dr. Brown noted that “PFS is the gold standard for measuring efficacy in CLL clinical trials. The ALPINE data showing superior efficacy and consistent benefit across patient subgroups including patients with high-risk del(17p)/TP53, along with a favorable cardiovascular safety profile, provide compelling evidence for BRUKINSA as a practice-changing Bruton’s tyrosine kinase (BTK) inhibitor for patients with CLL.”

“Brukinsa was specifically designed to maximize BTK occupancy and minimize off-target effects. Our clinical development programs were intended to test for a differentiated efficacy and safety profile,” said Mehrdad Mobasher, M.D., M.P.H., Chief Medical Officer, Hematology at BeiGene. “We believe the ALPINE PFS data and cardiac safety results for BRUKINSA, including an absence of cardiac death, demonstrate a meaningful advance in outcomes for patients with CLL.”

In this final analysis, Brukinsa achieved superior PFS over ibrutinib (HR: 0.65 [95% CI, 0.49-0.86] p=0.0024, for both Independent Review Committee [IRC] and investigator). At 24 months, the investigator-assessed PFS rates were 78.4% for Brukinsa compared to 65.9% with ibrutinib. The PFS benefit was observed across all major subgroups, including high-risk del(17p)/TP53 (HR: 0.52; [95% CI, 0.30-0.88]), as assessed by IRC. Brukinsa also demonstrated higher overall response rate (ORR), with a response rate of 80.4% versus 72.9% (two-sided p=0.0264), as assessed by IRC.

Brukinsa was generally well-tolerated with fewer adverse events leading to treatment discontinuation compared with ibrutinib (15.4% vs. 22.2%). There was a lower rate of cardiac disorders for Brukinsa compared with ibrutinib (21.3% vs 29.6%), and cardiac disorders leading to treatment discontinuation occurred in one Brukinsa patient versus 14 ibrutinib patients (0.3% vs. 4.3%). No patient receiving Brukinsa died due to a cardiac adverse event; six patients receiving ibrutinib experienced a fatal cardiac adverse event (0% vs. 1.9%). The most commonly reported treatment emergent adverse events (?20%) with Brukina and ibrutinib were diarrhea (16.0% vs. 24.1%), hypertension (14.8% vs. 11.1%), neutropenia (22.8% vs. 18.2%), COVID-19 (23.1% vs. 17.9%), and upper respiratory tract infection (21.0% vs. 14.2%).

CLL is the most common type of leukemia in adults, accounting for about one-quarter of new cases of leukemia in the United States. The condition is characterized by consecutive relapses, with response to therapy ultimately determining clinical benefit, including survival. BeiGene’s sNDA for BRUKINSA in CLL is currently under review with the FDA and has a target action date of January 20, 2023.

See -"Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia"- Jennifer R. Brown, M.D., Ph.D., Barbara Eichhorst, M.D., Peter Hillmen, M.B., Ch.B., Ph.D., Wojciech Jurczak, M.D., Ph.D., et al.-December 13, 2022 DOI: 10.1056/NEJMoa2211582.