THE SAFETY
OF BRUKINSA

OVERALL INCIDENCE OF ADVERSE REACTIONS (ARs)1,2

Adverse
Reactions1,2		 ARs in ≥10% of patients with WM (Cohort 1) Pooled data: ARs in
patients with hematologic
malignancies
BRUKINSA (n=101) Ibrutinib (n=98) BRUKINSA (N=1550)*
All Grades (%) Grades 3 or 4 (%) All Grades (%) Grades 3 or 4 (%) All Grades (%) Grade ≥3 (%)
Upper respiratory tract infection 44 0 40 2 39 2
Pneumonia 12 4 26 10 20 11
Urinary tract infection 11 0 13 2 13 2
Diarrhea 22 3 34 2 19 2
Nausea 18 0 13 1 11 0.2
Constipation 16 0 7 0 13 0.3
Vomiting 12 0 14 1 7 0.3
Fatigue 31 1 25 1 17 1
Pyrexia 16 4 13 2 10 0.8
Edema peripheral 12 0 20 0 4 0.2
Bruising 20 0 34 0 23 0.1
Rash 29 0 32 0 28 0.9
Pruritus 11 1 6 0 7 0.1
Musculoskeletal pain 45 9 39 1 30 2
Muscle spasms 10 0 28 1 5 0.1
Headache 18 1 14 1 11 0.4
Dizziness 13 1 12 0 11 0.3
Cough 16 0 18 0 19 0.1
Dyspnea 14 0 7 0 8 0.5
Hemorrhage 42 4 43 9 30 4
Hypertension 14 9 19 14 14 7

Safety in WM consistent with established BRUKINSA profile across B-cell malignancies1,2

The median follow-up time for Cohort 1 was 19.4 months.3

BRUKINSA had lower rates of:

Hypertension3

  • Ibrutinib patients experienced nearly 2-fold higher incidence rate of hypertension on an exposure-adjusted basis (BRUKINSA vs ibrutinib: 0.7% vs 1.2%, respectively)

Major hemorrhage3

  • Ibrutinib patients experienced nearly 2-fold higher incidence rate of major hemorrhage on an exposure-adjusted basis (BRUKINSA vs ibrutinib: 0.3% vs 0.6%, respectively)

*Chronic lymphocytic leukemia, Waldenström’s macroglobulinemia, mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma, hairy cell leukemia, diffuse large B-cell lymphoma, and Richter’s transformation.3

WM=Waldenström’s macroglobulinemia.

INCIDENCE OF LABORATORY ABNORMALITIES

Select laboratory abnormalities† (≥20%) that worsened from baseline in Cohort 1

Laboratory Abnormality1 BRUKINSA‡ Ibrutinib‡
All Grades (%) Grades 3 or 4 (%) All Grades (%) Grades 3 or 4 (%)
Hematologic abnormalities
Neutrophils decreased 50 24 34 9
Platelets decreased 35 8 39 5
Hemoglobin decreased 20 7 20 7
Chemistry abnormalities
Bilirubin increased 12 1.0 33 1.0
Calcium decreased 27 2.0 26 0
Creatinine increased 31 1.0 21 1.0
Glucose increased§ 45 2.3 33 2.3
Potassium increased 24 2.0 12 0
Urate increased 16 3.2 34 6
Phosphate decreased 20 3.1 18 0
BRUKINSA had a higher rate of neutropenia (BRUKINSA=29.7% vs ibrutinib=13.3%), not associated with increased infection (BRUKINSA=66.3% vs ibrutinib=67.3%)3

†Based on laboratory measurements.

‡The denominator used to calculate the rate varied from 86 to 101 based on the number of patients with a baseline value and at least 1 post-treatment value.

§Patients on study were not required to fast for lab tests.

INCIDENCE OF ATRIAL FIBRILLATION/FLUTTER

Adverse
Event3		 All Grades
n (%)		 Grade ≥3
n (%)
BRUKINSA
(n=101)		 Ibrutinib
(n=98)		 BRUKINSA
(n=101)		 Ibrutinib
(n=98)
Atrial fibrillation/flutter 2 (2) 15 (15) 0 (0) 4 (4)

BRUKINSA HAD LOWER RATES OF:

Atrial fibrillation/flutter2,3

  • Ibrutinib patients experienced nearly 10-fold higher incidence of atrial fibrillation/flutter on an exposure-adjusted basis (BRUKINSA vs ibrutinib: 0.1% vs 1.0%, respectively)
  • No incidences of Grade ≥3 atrial fibrillation or flutter in patients who received BRUKINSA

LOW RATE OF ATRIAL FIBRILLATION/FLUTTER
AND HYPERTENSION WITH BRUKINSA

Initial analysis (19 months)3

Rates of atrial fibrillation/flutter and hypertension with BRUKINSA® (zanubrutinib)
Adverse event trends
Incidence of atrial fibrillation/flutter and hypertension were lower in patients receiving BRUKINSA than in patients taking ibrutinib.4
In a ~4-year follow-up consistent with the primary analysis, BRUKINSA continued to demonstrate lower rates of atrial fibrillation/flutter and hypertension4

The median follow-up time was 19.4 months for Cohort 1.

ADVERSE REACTIONS OF INTEREST AND THEIR PREVALENCE OVER TIME4

Long-term analysis (44 months)4

Data for adverse reactions of interest in WM

DOSE REDUCTIONS AND DISCONTINUATION RATE
DUE TO ADVERSE EVENTS (AEs) IN ASPEN (STUDY 302)3

Initial analysis (19 months)3

Dose reductions due to AEs

BRUKINSA

Cohort 1 (n=101)

14

of patients

Ibrutinib

(n=98)

23

of patients

Discontinuation rate due to AEs

BRUKINSA

Cohort 1 (n=101)

4

of patients

Ibrutinib

(n=98)

9

of patients

Median duration of treatment: 25 months2

In a ~4-year follow-up consistent with the primary analysis, fewer AEs leading to treatment discontinuation and dose reductions occurred with BRUKINSA4

Dr Anthony Nguyen discusses the safety profile of BRUKINSA vs ibrutinib in WM

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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. BeiGene USA, Inc.; 2025. 2. Data on file. BeiGene USA, Inc. 3. Tam CS, Opat S, D’Sa S, et al. A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: the ASPEN study. Blood. 2020;136(18):2038-2050. 4. Tam CS, Garcia-Sanz R, Opat S, et al. ASPEN: long-term follow-up results of a phase 3 randomized trial of zanubrutinib versus ibrutinib in patients with Waldenström macroglobulinemia. Poster presented at: American Society of Clinical Oncology (ASCO) 2022 Annual Meeting; June 3-7, 2022. Abstract 7521.