Orlando, Florida — December 8, 2025 — Leads & Copy — BeOne Medicines Ltd. presented data at the 67th ASH Annual Meeting and Exposition in Orlando, Florida, reinforcing its position in chronic lymphocytic leukemia (CLL) innovation. The data highlights the hematology portfolio, with BRUKINSA® (zanubrutinib) emerging as a foundational Bruton’s tyrosine kinase inhibitor (BTKi).
According to Amit Agarwal, M.D., Ph.D., Chief Medical Officer, Hematology, BeOne, the data presented highlights the strength of BRUKINSA and the potential of BGB-16673. Agarwal noted that long-term data are crucial in CLL, and BRUKINSA continues to provide high levels of durable progression-free and overall survival. He added that BGB-16673, a BTK degrader with over 800 patients dosed, represents the next wave of innovation in oncology.
BRUKINSA has demonstrated long-term efficacy and a favorable safety profile over six years of follow-up in treatment-naïve CLL/SLL.
The SEQUOIA (NCT03336333) Phase 3 trial showed BRUKINSA’s progression-free survival (PFS) superiority versus bendamustine plus rituximab (BR). Key findings from Arms A, B, and C included an estimated 74% PFS at six years for BRUKINSA compared to 32% for BR in treatment-naïve CLL or small lymphocytic lymphoma (SLL). COVID-19 adjusted PFS rates were 77% for BRUKINSA and 33% for BR. Overall survival (OS) at 72 months was 84% for BRUKINSA and 80% for BR, with COVID-19 adjusted rates of 88% and 82%, respectively. In patients with del(17p), the six-year PFS was 64% (65% after COVID-19 adjustment) and the 72-month OS was 83%. The safety profile remained consistent with prior studies, with no new safety signals identified.
Constantine Tam, M.B.B.S., M.D., Head of Lymphoma Service at Alfred Health and Professor of Haematology at Monash University, stated that the longer follow-up from SEQUOIA strengthens the continuous use of zanubrutinib. Tam noted that patients showed durable disease control and consistent safety, raising the bar for CLL patients, including those with harder-to-treat CLL.
Arm D of the trial examined BRUKINSA plus venetoclax in patients with or without del(17p) and/or TP53 mutations. In the overall patient population, where 58% had del(17p) and/or TP53 mutation, the median PFS was not reached, and the 36-month PFS rate was 87%. For patients with del(17p) and/or TP53 mutation, the 36-month PFS rate was 87%, while it was 89% for those without these mutations. Following the combination period, 42 patients continued BRUKINSA monotherapy. At 12 months, peripheral blood undetectable minimal residual disease (uMRD) was maintained in 100% of patients without del(17p) and TP53. At 18 months, uMRD was maintained in 92% of patients with del(17p) and/or TP53 mutation. The safety profile of the combination was generally tolerable, with no unexpected safety signals.
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) now recommend zanubrutinib plus venetoclax as a preferred first-line regimen for CLL/SLL.
New patient-reported outcomes data in R/R CLL suggest BRUKINSA may offer a more manageable side effect profile, with up to six years of follow-up data supporting its foundational role in CLL/SLL.
The ALPINE (NCT03734016) Phase 3 study of BRUKINSA versus ibrutinib in patients with R/R CLL/SLL who received ≥1 prior systemic therapy highlighted symptom-based progression-free survival as a clinically relevant and patient-centric endpoint. The study demonstrated a statistically and clinically meaningful association between longitudinal symptom deterioration and disease progression using joint modeling. Deterioration in patient-reported fatigue, insomnia, and nausea/vomiting emerged as strong symptomatic indicators of disease progression. Patients on BRUKINSA showed reduced risk of symptom deterioration and had lower odds of symptom worsening for nausea/vomiting, fatigue, pain, and insomnia compared to ibrutinib.
Up to 73.5 months of follow-up from the BRUKINSA arm of ALPINE (LTE-1) showed a median PFS for all patients of 52.5 months, and the 60-month PFS rate was 47.3% (50.4% adjusted for COVID-19). Among patients with del(17p), the median PFS was 49.9 months, and the 60-month PFS rate was 38.2% (40.5% adjusted for COVID-19). The prevalence of most adverse events of special interest remained stable year-over-year.
Clinical data from the CaDAnCe-101 (NCT05006716) Phase 1/2 study evaluating BGB-16673 monotherapy in patients with B-cell malignancies showed responses across R/R CLL/SLL patient types, including those previously treated with BTK inhibitors, BCL2 inhibitors, noncovalent BTK inhibitors, and those with BTK inhibitor resistance mutations. With a median follow-up of 19.8 months, 54.4% of patients remain on treatment. Across all doses, the ORR was 85.3% and the CR/CR with incomplete count recovery (CRi) rate was 2.9%, with responses deepening over time. In the group dosed at the RP2D (200 mg QD), ORR was 94.4%. For patients with prior covalent BTK inhibitor, BCL2i, and noncovalent BTK inhibitor treatment, ORR was 75.0%. The 12- and 18-month PFS rates were 73.5% and 65.9%, respectively. BGB-16673 was generally well tolerated in this heavily pretreated population, with no treatment-related deaths and no new toxicities identified and with a median treatment duration of 13.6 months.
Amit Agarwal, M.D., Ph.D. is Chief Medical Officer, Hematology, BeOne.
For more information about BeOne at the 2025 ASH Annual Meeting, visit congress.beonemedicines.com.
Chronic lymphocytic leukemia (CLL) is a life-threatening cancer of adults, with abnormal leukemic B lymphocytes arising from the bone marrow. CLL is the most common type of leukemia in adults, accounting for about one-third of new cases.
BGB-16673 is a potential first-in-class Bruton’s tyrosine kinase (BTK) protein degrader and is the most advanced protein degrader in the clinic, with nearly 800 patients dosed to date in an extensive global clinical development program. This program includes three randomized Phase 3 trials in R/R CLL, including the head-to-head Phase 3 trial versus pirtobrutinib, which began enrolling in Q4 2025. Originating from BeOne’s chimeric degradation activation compound (CDAC) platform, BGB-16673 is designed to promote the degradation, or breakdown, of both wildtype and mutant forms of BTK, including those that commonly result in resistance to BTK inhibitors in patients who experience progressive disease.
The U.S. Food and Drug Administration (FDA) granted Fast Track Designation to BGB-16673 for the treatment of adult patients with relapsed or refractory (R/R) chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL), and adult patients with R/R mantle cell lymphoma (MCL). Additionally, the European Medicines Agency (EMA) granted BGB-16673 PRIority MEdicines (PRIME) designation for the treatment of patients with Waldenstrom’s macroglobulinemia (WM) previously treated with a BTK inhibitor.
BRUKINSA is an orally available, small molecule inhibitor of Bruton’s tyrosine kinase (BTK) designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease-relevant tissues.
BRUKINSA has the broadest label globally of any BTK inhibitor and is the only BTK inhibitor to provide the flexibility of once or twice daily dosing and to demonstrate superiority to another BTK inhibitor in a Phase 3 study. The global BRUKINSA clinical development program includes about 7,100 patients enrolled in 30 countries and regions across more than 35 trials. BRUKINSA is approved in more than 75 markets, and more than 247,000 patients have been treated globally.
Serious adverse reactions, including fatal events, have occurred with BRUKINSA, including hemorrhage, infections, cytopenias, second primary malignancies, cardiac arrhythmias, and hepatotoxicity (including drug-induced liver injury). In the pooled safety population (N=1729), the most common adverse reactions (≥30%), including laboratory abnormalities, in patients who received BRUKINSA were neutrophil count decreased (51%), platelet count decreased (41%), upper respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain (31%).
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Source: BeOne Medicines
