SUPERIOR EFFICACY ACROSS LINES OF THERAPY

Sustained efficacy at ~3.5-year and ~5-year milestone analyses

1L: SEQUOIA

SUPERIOR PFS vs BR IN PATIENTS WITHOUT DEL(17p); SUSTAINED RESULTS AT THE ~5-YEAR MILESTONE1-4

58% relative risk reduction in disease progression or death with BRUKINSA vs BR at the superiority analysis
(Cohort 1; primary endpoint; HR=0.42; 95% CI: 0.28, 0.63; p<0.0001; median follow-up: 26.2 months)*†

71% relative risk reduction in disease progression or death with BRUKINSA vs BR at ~5 years‡

Cohort 1: patients without del(17p)

KM curve showing superior PFS data vs BR for SEQUOIA

*Median PFS was not reached in either arm at the initial analysis.1,2

†Prespecified analysis assessed by IRC.2

‡Analysis is exploratory and descriptive in nature.

CONSISTENT PFS IN PATIENTS WITH DEL(17p) +/-TP53 AND ulgHV3-9

In the largest prospective study of 1L CLL patients with del(17p), BRUKINSA
delivered an unmatched PFS rate*† 4-9

Cohort 2: patients with del(17p) +/-TP53

KM curve showing superior PFS data vs BR for SEQUOIA
KM curve showing superior PFS data vs BR for SEQUOIA

79% relative risk reduction in
disease progression or death with
BRUKINSA vs BR in patients with uIgHV at ~5 years*3

Cohort 1: patients without del(17p)

KM curve showing PFS data for patients with del(17p) in the SEQUOIA BRUKINSA® (zanubrutinib)-only arm

*Analyses are exploratory and descriptive in nature.

†Data are presented in patients with del(17p), confirmed by central laboratory (n=110).4

IN PATIENTS WITHOUT DEL(17p):
PFS GENERALLY FAVORED BRUKINSA AT ~5 YEARS, REGARDLESS OF MUTATION STATUS*†3

PFS data from SEQUOIA for patients without del(17p)/TP53 taking BRUKINSA® (zanubrutinib)
PFS data from SEQUOIA for patients without del(17p)/TP53 taking BRUKINSA® (zanubrutinib)
PFS data from SEQUOIA for patients without del(17p)/TP53 taking BRUKINSA® (zanubrutinib)

*Assessed by investigator.3

†Median follow-up at the long-term analysis: 61.2 months.3

‡The hazard ratio and 95% CI were assessed using a stratified (for all patients) or unstratified (for subgroup) Cox regression model with the BR arm as the reference arm.3

§Cytopenia: anemia (hemoglobin ≤110 g/L), thrombocytopenia (platelet count ≤100 x 109/L), or neutropenia (absolute neutrophil count ≤1.5 x 109/L).3

On the basis of monosomy 13q mutation results.3

HIGH ORR IN PATIENTS WITHOUT DEL(17p) AND WITH DEL(17p) IN THE INITIAL ANALYSIS1,2

Cohort 1: without del(17p)

secondary endpoint*

93% ORR

with BRUKINSA (n=241) at ~2 years

(95% CI: 89.0, 96.0) vs 85%

with BR (n=238) (95% CI: 80.0, 90.0)

Cohort 2: with del(17p)

secondary endpoint†

88% ORR

with BRUKINSA (n=110)
(95% CI: 81.0, 94.0)

*Prespecified analysis assessed by IRC; median follow-up of 26.2 months.2

†Prespecified analysis assessed by IRC; median follow-up of 30.5 months.2

1L=first line; BR=bendamustine+rituximab; CI=confidence interval; HR=hazard ratio; IRC=independent review committee; LDi=longest diameter; ORR=overall response rate; PFS=progression-free survival; VAF=variant allele frequency.

READ THE SEQUOIA (1L) PUBLICATION READ THE SEQUOIA ~5-YEAR MILESTONE ANALYSIS
2L: ALPINE

THE ONLY BTKi WITH SUPERIOR EFFICACY vs IBRUTINIB; SUSTAINED RESULTS AT THE ~3.5-YEAR MILESTONE1,10,11

35% relative risk reduction in disease progression or death with BRUKINSA vs ibrutinib in all-comers at the superiority analysis
(secondary endpoint; HR=0.65; 95% CI: 0.49, 0.86; p=0.0024; median follow-up: 31 months)*

32% relative risk reduction in disease progression or death with BRUKINSA vs ibrutinib at ~3.5 years†

all-comer population

KM curve showing PFS data for the all-comer population in ALPINE

49% relative risk reduction in disease progression or death vs ibrutinib†

patients with del(17p) +/-TP53

KM curve showing PFS data for patients with del(17p)/TP53 in ALPINE

*Prespecified analysis assessed by both IRC and investigator with similar results. Median PFS has not yet been reached with BRUKINSA vs 34 months with ibrutinib.10

†Analyses are exploratory and descriptive in nature.

CONSISTENT PFS vs IBRUTINIB AT INITIAL ANALYSIS, REGARDLESS OF MUTATION STATUS*†10

Consistent PFS across subgroups in ALPINE
Consistent PFS across subgroups in ALPINE
Consistent PFS across subgroups in ALPINE

All subgroup analyses are exploratory and descriptive in nature.

*Assessed by both IRC and investigator with similar results.10

†Median follow-up at the initial analysis: 31 months.1

‡Hazard ratio and 95% CI were unstratified for subgroups.10

THE ONLY BTKi TO ACHIEVE SUPERIOR ORR vs IBRUTINIB1

Initial analysis (25 months for ORR)

Bar chart showing ORR data from ALPINE

Median follow-up: 24.7 months12

With BRUKINSA, 92% of patients sustained a response vs 86% with ibrutinib at 1 year1

Statistical analysis for ORR was conducted for noninferiority. When noninferiority was met, superiority was tested.10

*Assessed by both IRC and investigator with similar results.1,10

BRUKINSA DEMONSTRATED MORE COMPLETE RESPONSES OVER TIME vs IBRUTINIB11

Bar chart showing complete responses over time (PR+PR-L+nPR and CR+CRi) for BRUKINSA (zanubrutinib) vs ibrutinib from ALPINE
Bar chart showing complete responses over time (PR+PR-L+nPR and CR+CRi) for BRUKINSA (zanubrutinib) vs ibrutinib from ALPINE
Bar chart showing complete responses over time (PR+PR-L+nPR and CR+CRi) for BRUKINSA (zanubrutinib) vs ibrutinib from ALPINE

Exploratory analyses.

CONSISTENT ORR vs IBRUTINIB AT INITIAL ANALYSIS, REGARDLESS OF MUTATION STATUS10

Consistent ORR across subgroups in ALPINE
Consistent ORR across subgroups in ALPINE
Consistent ORR across subgroups in ALPINE

All subgroup analyses are exploratory and descriptive in nature.

Assessed by both IRC and investigator with similar results. Median follow-up of 24.7 months.1,10,12

2L=second line; BTKi=Bruton’s tyrosine kinase inhibitor; CI=confidence interval; CR=complete response; CRi=complete response with absolute neutrophil count <1000/µL; ECOG PS=Eastern Cooperative Oncology Group performance status; HR=hazard ratio; IRC=independent review committee; nPR=nodular partial response; ORR=overall response rate; PFS=progression-free survival; PR=partial response; PR–L=partial response with lymphocytosis.

READ THE ALPINE (2L) PUBLICATION READ THE ALPINE ~3.5-YEAR MILESTONE ANALYSIS

Dr Anthony Nguyen discusses efficacy data across mutations in CLL

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IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage

Fatal and serious hemorrhage has occurred in patients with hematological malignancies treated with BRUKINSA. Grade 3 or higher hemorrhage including intracranial and gastrointestinal hemorrhage, hematuria, and hemothorax was reported in 3.8% of patients treated with BRUKINSA in clinical trials, with fatalities occurring in 0.2% of patients. Bleeding of any grade, excluding purpura and petechiae, occurred in 32% of patients.

Bleeding has occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Coadministration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.

Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days before and after surgery depending upon the type of surgery and the risk of bleeding.

Infections

Fatal and serious infections (including bacterial, viral, or fungal infections) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA. Grade 3 or higher infections occurred in 26% of patients, most commonly pneumonia (7.9%), with fatal infections occurring in 3.2% of patients. Infections due to hepatitis B virus (HBV) reactivation have occurred.

Consider prophylaxis for herpes simplex virus, pneumocystis jirovecii pneumonia, and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (21%), thrombocytopenia (8%) and anemia (8%) based on laboratory measurements, developed in patients treated with BRUKINSA. Grade 4 neutropenia occurred in 10% of patients, and Grade 4 thrombocytopenia occurred in 2.5% of patients.

Monitor complete blood counts regularly during treatment and interrupt treatment, reduce the dose, or discontinue treatment as warranted. Treat using growth factor or transfusions, as needed.

Second Primary Malignancies

Second primary malignancies, including non-skin carcinoma, have occurred in 14% of patients treated with BRUKINSA. The most frequent second primary malignancy was non-melanoma skin cancers (8%), followed by other solid tumors in 7% of the patients (including melanoma in 1% of patients) and hematologic malignancies (0.7%). Advise patients to use sun protection and monitor patients for the development of second primary malignancies.

Cardiac Arrhythmias

Serious cardiac arrhythmias have occurred in patients treated with BRUKINSA. Atrial fibrillation and atrial flutter were reported in 4.4% of patients treated with BRUKINSA, including Grade 3 or higher cases in 1.9% of patients. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher ventricular arrhythmias were reported in 0.3% of patients.

Monitor for signs and symptoms of cardiac arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea, chest discomfort), manage appropriately, and consider the risks and benefits of continued BRUKINSA treatment.

Hepatotoxicity, Including Drug-Induced Liver Injury

Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of drug-induced liver injury (DILI), has occurred in patients treated with Bruton tyrosine kinase inhibitors, including BRUKINSA.

Evaluate bilirubin and transaminases at baseline and throughout treatment with BRUKINSA. For patients who develop abnormal liver tests after BRUKINSA, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold BRUKINSA. Upon confirmation of DILI, discontinue BRUKINSA.

Embryo-Fetal Toxicity

Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity, including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for 1 week after the last dose. Advise men to avoid fathering a child during treatment and for 1 week after the last dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

ADVERSE REACTIONS

The most common adverse reactions (≥30%), including laboratory abnormalities, in patients who received BRUKINSA (N=1729) are decreased neutrophil count (51%), decreased platelet count (41%), upper respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain (31%).

DRUG INTERACTIONS

CYP3A Inhibitors: When BRUKINSA is coadministered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For coadministration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.

CYP3A Inducers: Avoid coadministration with strong or moderate CYP3A inducers. Dose adjustment may be recommended with moderate CYP3A inducers.

SPECIFIC POPULATIONS

Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily.

INDICATIONS

BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with:

  • Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)
  • Waldenström’s macroglobulinemia (WM)
  • Mantle cell lymphoma (MCL) who have received at least one prior therapy
  • Relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen
  • Relapsed or refractory follicular lymphoma (FL), in combination with obinutuzumab, after two or more lines of systemic therapy

The MCL, MZL and FL indications are approved under accelerated approval based on overall response rate and durability of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

Please see full Prescribing Information.

References: 1. BRUKINSA. Package insert. BeOne Medicines USA, Inc.; 2025. 2. Tam CS, Brown JR, Kahl BS, et al. Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Lancet Oncol. 2022;23(8):1031-1043. 3. Shadman M, Munir T, Robak T, et al. Zanubrutinib versus bendamustine and rituximab in patients with treatment-naïve chronic lymphocytic leukemia/small lymphocytic lymphoma: median 5-year follow-up of SEQUOIA. J Clin Oncol. 2025;43(7):780-787. 4. Tam CS, Ghia P, Shadman M, et al. SEQUOIA 5-year follow-up in arm C: frontline zanubrutinib monotherapy in patients with del(17p) and treatment-naive CLL/SLL [oral presentation]. Presented at: American Society of Clinical Oncology (ASCO) 2025 Annual Meeting; May 30-June 3, 2025. 5. Shadman M, Munir T, Ma S, et al. Combination of zanubrutinib + venetoclax for treatment-naive CLL/SLL: results in SEQUOIA Arm D. Presented at: American Society of Clinical Oncology (ASCO) 2025 Annual Meeting; May 30-June 3, 2025. 6. Davids MS, Ryan CE, Lampson BL, et al. Phase II study of acalabrutinib, venetoclax, and obinutuzumab in a treatment-naïve chronic lymphocytic leukemia population enriched for high-risk disease. J Clin Oncol. 2025;43(7):788-799. 7. Clinical Care Options (CCO). ELEVATE-TN: 5-yr update of acalabrutinib ± obinutuzumab vs obinutuzumab + chlorambucil in treatment-naive CLL. Presented at: American Society of Clinical Oncology (ASCO) 2022 Annual Meeting; June 3-7, 2022. 8. Al-Sawaf O, Robrecht S, Zhang C, et al. Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized phase 3 CLL14 study. Blood. 2024;144(18):1924-1935. 9. Wierda WG, Jacobs R, Barr PM, et al. Outcomes in high-risk subgroups after fixed-duration ibrutinib + venetoclax for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): up to 5.5 years of follow-up in the phase 2 CAPTIVATE study. J Clin Oncol. 2024;42(16[suppl]). Abstract 7009. 10. Brown JR, Eichhorst B, Hillmen P, et al. Zanubrutinib or ibrutinib in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2023;388(4):319-332. 11. Brown JR, Eichhorst B, Lamanna N, et al. Sustained benefit of zanubrutinib vs ibrutinib in patients with R/R CLL/SLL: final comparative analysis of ALPINE. Blood. 2024;144(26):2706-2717. 12. Data on file. BeiGene USA, Inc.