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=847)*
All Grades (%) Grades 3 or 4 (%) All Grades (%) Grades 3 or 4 (%) All Grades (%) Grades ≥3 (%)
Upper respiratory tract infection 44 0 40 2 47 3
Pneumonia 12 4 26 10 21 11
Urinay tract infection 11 0 13 2 16 3
Diarrhea 22 3 34 2 24 2
Nausea 18 0 13 1 12 0.4
Constipation 16 0 7 0 16 0.4
Vomiting 12 0 14 1 8 0.5
Fatigue 31 1 25 1 20 2
Pyrexia 16 4 13 2 13 2
Edema peripheral 12 0 20 0 9 0.4
Bruising 20 0 34 0 25 0.1
Rash 29 0 32 0 31 0.7
Pruritus 11 1 6 0 8 0.1
Musculoskeletal pain 45 9 39 1 30 3
Muscle spasms 10 0 28 1 6 0.0
Headache 18 1 14 1 13 0.6
Dizziness 13 1 12 0 11 0.4
Cough 16 0 18 0 23 0.1
Dyspnea 14 0 7 0 9 0.8
Hemorrhage 42 4 43 9 35 3
Hypertension 14 9 19 14 12 5

Safety in WM consistent with established BRUKINSA
profile across B-cell malignancies1,3

The median follow-up time for Cohort 1 was 19.4 months.4


BRUKINSA demonstrated lower rates of:

Hypertension4

  • Ibrutinib patients experienced nearly 2-fold higher incidence rate of hypertension on an exposure-adjusted basis

Major hemorrhage4

  • Ibrutinib patients experienced ~2-fold higher incidence rate of major hemorrhage on an exposure-adjusted basis

*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


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


Neutropenia in BRUKINSA patients was not associated
with an increased risk of infection.4

Growth factor support was allowed in
both treatment arms.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 one post-treatment value.

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



INCIDENCE OF ATRIAL FIBRILLATION/FLUTTER


Adverse Event4 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 DEMONSTRATED LOWER RATES OF:

Atrial fibrillation/flutter4


  • Ibrutinib patients experienced ~10-fold higher incidence of atrial fibrillation/flutter on an exposure-adjusted basis
  • No incidences of Grade ≥3 atrial fibrillation or flutter in patients who received BRUKINSA

Low rate of atrial fibrillation/flutter
and hypertension with BRUKINSA


Brukinsa

Adverse event trends

Among patients who received ibrutinib, incidence of atrial fibrillation/flutter and hypertension increased over time4

Dose reductions and discontinuation rates
DUE TO ADVERSE EVENTS (AEs) in ASPEN (Study 302)4


Dose reductions
due to AEs
BRUKINSACohort 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



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