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 (%) | Grades ≥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
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 1.3
ADVERSE REACTIONS OF INTEREST AND THEIR PREVALENCE OVER TIME4
Long-term analysis (44 months)4
Dose reductions and discontinuation rate
DUE TO ADVERSE EVENTS (AEs) in ASPEN (Study 302)3
Initial analysis (19 months)3
due to AEs
due to AEs
In a ~4-year follow-up consistent with the primary analysis, fewer AEs leading to treatment discontinuation and dose reductions occurred with BRUKINSA4
