Safety data for BRUKINSA® (zanubrutinib) for CLL/SLL

BRUKINSA patients can call the myBeiGene^® patient support program to talk to a dedicated nurse: 1-833-BEIGENE (1-833-234-4363)

CONSISTENT SAFETY ACROSS LINES OF THERAPY

FIRST LINE

SEQUOIA (STUDY 304)
COHORT 1: OVERALL INCIDENCE OF ADVERSE REACTIONS (ARs)^1,2

Adverse Reactions	ARs in ≥10% of Patients Without Del(17p)				Pooled Safety Population*
	BRUKINSA (n=240)		BR (n=227)		BRUKINSA (N=1550)
	All Grades (%)	Grade ≥3 (%)	All Grades (%)	Grade ≥3 (%)	All Grades (%)	Grade ≥3 (%)
Musculoskeletal pain	33	2	17	0.4	30	2
Upper respiratory tract infection	28	1	15	0.9	39	2
Pneumonia	13^†	5	8^‡	4	20	11
Hemorrhage	27^†	4	4	0.4	30	4
Hypertension	14	7	5	3	14	7
Rash	24	1	30	5	28	0.9
Bruising	24	0	3	0	23	0.1
Cough	15	0	10	0	19	0.1
Diarrhea	14	0.8	12^‡	0.9	19	2
Constipation	10	0.4	18	0	13	0.3
Nausea	10	0	33	1	11	0.2
Fatigue	14	1	21	2	17	1
Second primary malignancy	13^†	6	1	0.4	13	6
Headache	12	0	8	0	11	0.4
Dizziness	11	0.8	5	0	11	0.3

*Includes 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.²

^†Includes 3 fatal outcomes.¹

^‡Includes 2 fatal outcomes.¹

SEQUOIA (STUDY 304)
COHORT 2: OVERALL INCIDENCE OF ARs^1,2

Adverse Reactions	ARs in ≥10% of Patients With Del(17p)		Pooled Safety Population*
	BRUKINSA (n=111)		BRUKINSA (N=1550)
	All Grades (%)	Grade ≥3 (%)	All Grades (%)	Grade ≥3 (%)
Upper respiratory tract infection	38	0	39	2
Pneumonia	20^†	8	20	11
Musculoskeletal pain	38	3	30	2
Rash	28	0	28	0.9
Bruising	26	0.9	23	0.1
Hemorrhage	28	5	30	4
Hypertension	11	5	14	7
Second primary malignancy	22^‡	6	13	6
Diarrhea	18	0.9	19	2
Nausea	16	0	11	0.2
Constipation	15	0	13	0.3
Abdominal pain	12	2	10	0.6
Cough	18	0	19	0.1
Dyspnea	13	0	8	0.5
Fatigue	14	0.9	17	1
Headache	11	2	11	0.4

^†Includes 1 fatal outcome.¹

^‡Includes non-melanoma skin cancer in 13%.¹

SEQUOIA (STUDY 304): INCIDENCE OF LABORATORY ABNORMALITIES¹Select Lab Abnormalities (≥20%) That Worsened From Baseline in Cohorts 1 and 2

Laboratory Abnormality	Cohort 1: Patients Without Del(17p)				Cohort 2: Patients With Del(17p)
	BRUKINSA (n=239)*		BR (n=227)		BRUKINSA (n=111)^†
	All Grades (%)	Grade ≥3 (%)	All Grades (%)	Grade ≥3 (%)	All Grades (%)	Grade ≥3 (%)
Neutrophils decreased	37	15	80	53	42	19^‡
Hemoglobin decreased	29	3	66	8	26	4
Platelets decreased	27	2	61	11	23	0.9
Leukocytes increased	21^§	21	0.4	0.4	NR	NR
Glucose increased^¶	55	7	67	10	52	6
Creatinine increased	22	0.8	18	0.4	27	0.9
Magnesium increased	22	0	14	0.4	31	0
Alanine aminotransferase increased	21	2	23	2	NR	NR

*In Cohort 1, the denominator used to calculate the rate varied from 239 to 227 based on the number of patients with a baseline value and at least 1 post-treatment value. Grading is based on NCI CTCAE criteria.

^†In Cohort 2, the denominator used to calculate the rate varied from 110 to 111 based on the number of patients with a baseline value and at least 1 post-treatment value. Grading is based on NCI CTCAE criteria.

^‡Grade 4, 9%.

^§Lymphocytes increased in 15%.

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

SEQUOIA (STUDY 304): SELECT ADVERSE EVENTS (AEs) OF SPECIAL INTEREST^1-3

Adverse Events	SEQUOIA				Pooled Safety Population*
	BRUKINSA (n=240)		BR (n=227)		BRUKINSA (N=1550)
	All Grades (%)	Grade ≥3 (%)	All Grades (%)	Grade ≥3 (%)	All Grades (%)	Grade ≥3 (%)
Fatigue	12	1	15	0.9	17	1
Headache	11	0	7	0	11	0.4
Myalgia	4	0	1	0	4	0.4
Arthralgia	13	0.8	9	0.4	14	0.7
Atrial fibrillation/flutter^†	3	0.4	3	1	4	2
Hypertension	14	6	11	5	14	7
Major bleeding^‡	5	4	2	2	5	4

^†Includes rates of atrial fibrillation only; does not include flutter.²

^‡Major bleeding includes subdural hematoma or subdural hemorrhage.

SEQUOIA (STUDY 304):
LOWER RATES OF DOSE REDUCTIONS AND DISCONTINUATION DUE TO AEs³

AE=adverse event; AR=adverse reaction; BR=bendamustine+rituximab; NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events; NR=not reported.

SECOND LINE

ALPINE (STUDY 305): OVERALL INCIDENCE OF ADVERSE REACTIONS (ARs)^1,2

Adverse Reactions	ARs in ≥10% of Patients				Pooled Safety Population*
	BRUKINSA (n=324)		Ibrutinib (n=324)		BRUKINSA (N=1550)
	All Grades (%)	Grade ≥3 (%)	All Grades (%)	Grade ≥3 (%)	All Grades (%)	Grade ≥3 (%)
Upper respiratory tract infection	27	1	22	1	39	2
Pneumonia	18^†	9	19^‡	11	20	11
COVID-19	14^†	7	10^‡	5	5	3
Musculoskeletal pain	26	0.6	28	0.6	30	2
Hemorrhage	24^†	3	26^‡	4	30	4
Hypertension	19	13	20	13	14	7
Rash	20	1	21	0.9	28	0.9
Bruising	16	0	14	0	23	0.1
Diarrhea	14	2	22	0.9	19	2
Fatigue	13	0.9	14	0.9	17	1
Cough	11	0.3	11	0	19	0.1
Dizziness	10	0	7	0	11	0.3

Rates of hypertension were comparable between BRUKINSA and ibrutinib¹

A medical history of hypertension was reported in more than half of these patient events for both BRUKINSA and ibrutinib²

^†Includes fatal outcomes: pneumonia (9 patients), COVID-19 (8 patients), and hemorrhage (1 patient).¹

^‡Includes fatal outcomes: pneumonia (10 patients), COVID-19 (9 patients), and hemorrhage (2 patients).¹

ALPINE (STUDY 305): INCIDENCE OF LAB ABNORMALITIES¹Select Lab Abnormalities (≥20%) That Worsened From Baseline

Laboratory Abnormality	BRUKINSA (n=321)		Ibrutinib (n=321)*
Laboratory Abnormality	All Grades (%)	Grade ≥3 (%)	All Grades (%)	Grade ≥3 (%)
Neutrophils decreased	43	15	33	16
Hemoglobin decreased	28	4	32	4
Lymphocytes increased	24	19	26	19
Platelets decreased	22	4	24	3
Glucose increased^†	52	5	29	3
Creatinine increased	26	0	23	0
Phosphate decreased	21	3	13	2
Calcium decreased	21	0.6	29	0

*The denominator used to calculate rates of lab abnormalities varied from 320 to 321 in the ibrutinib arm based on the number of patients with a baseline value and at least 1 post-treatment value. Grading is based on NCI CTCAE criteria.

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

LOWER RATES OF CARDIAC DISORDERS, INCLUDING AFIB/FLUTTER, AND NO CARDIAC DEATHS vs IBRUTINIB*^4,5

*Assessed by both IRC and investigator with similar results. Median duration of treatment: 28.4 months for BRUKINSA and 24.3 months for ibrutinib.⁴

^†Cardiac disorders is a grouped term that includes atrial fibrillation and atrial flutter.⁴

	BRUKINSA (n=324)	Ibrutinib (n=324)
Cardiac adverse events	69 (21.3%)	96 (29.6%)
Serious cardiac adverse events	6 (1.9%)	25 (7.7%)
Cardiac adverse events leading to treatment discontinuation*	1 (0.3%)	14 (4.3%)
Fatal cardiac events	0 (0%)	6 (1.9%)

*BRUKINSA cardiac-related discontinuation in 1 patient was for ventricular extrasystoles. Ibrutinib cardiac-related discontinuations were for atrial fibrillation (5), cardiac arrest (2), cardiac failure (2), cardiac failure acute (1), congestive cardiomyopathy (1), myocardial infarction (1), palpitations (1), and ventricular fibrillation (1).⁴

There were 6 fatal cardiac events in patients treated with ibrutinib and none with BRUKINSA⁴

Assessed by both IRC and investigator with similar results. Median duration of treatment: 28.4 months for BRUKINSA and 24.3 months for ibrutinib.⁴

SELECT ADVERSE REACTIONS OF SPECIAL INTEREST IN ALPINE (STUDY 305)^1,2,4

Adverse Reactions	ALPINE				Pooled Safety Population*
	BRUKINSA (n=324)		Ibrutinib (n=324)		BRUKINSA (N=1550)
	All Grades (%)	Grade ≥3 (%)	All Grades (%)	Grade ≥3 (%)	All Grades (%)	Grade ≥3 (%)
Fatigue	13	0.9	14	0.9	17	1
Headache	8	0	9	0	11	0.4
Myalgia	3	0	4	0	4	0.4
Arthralgia	14	0	15	0.3	14	0.7
Atrial ﬁbrillation and ﬂutter	5	3	13	4	4	2
Hypertension	19	13	20	13	14	7
Major hemorrhage^†	4	3	4	4	5	4

^†Hematuria was the most common major hemorrhage.²

ALPINE (STUDY 305): LOWER RATES OF DOSE REDUCTIONS AND DISCONTINUATION DUE TO ADVERSE EVENTS (AEs)⁴

1 patient in the BRUKINSA arm discontinued treatment due to a cardiac AE vs 14 patients in the ibrutinib arm*

AE=adverse event; afib=atrial fibrillation; AR=adverse reaction; IRC=independent review committee; NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events.

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

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LONG-TERM DATA*

STUDY 003:

A global supportive Phase 1/2, open-label, single-arm trial that included patients with treatment-naïve or relapsed/refractory CLL/SLL and evaluated ~4 years of safety and ~3 years of efficacy data.⁶

ADVERSE EVENTS OF SPECIAL INTEREST DECREASED OVER TIME⁶Incidence of Treatment-Emergent Adverse Events (TEAEs) Over Time (Grade ≥3)

Atrial fibrillation remained consistently low
No new safety signals
Low discontinuation rate of 10% over 4 years (N=123)

TEAEs were consistent with the overall safety profile of BRUKINSA

Overall median duration of treatment: 43 months.

Exploratory long-term analysis; all data are descriptive in nature.

Study 003 was a global supportive Phase 1/2 trial for 1L and 2L CLL.

*Assessed by IRC.

1L=first line; 2L=second line; CLL=chronic lymphocytic leukemia; IRC=independent review committee; SLL=small lymphocytic lymphoma.

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IMPORTANT SAFETY INFORMATION

What should I tell my healthcare provider before taking BRUKINSA?

Before taking BRUKINSA, tell your healthcare provider about all of your medical conditions, including if you:

have bleeding problems.
have had recent surgery or plan to have surgery. Your healthcare provider may stop BRUKINSA for any planned medical, surgical, or dental procedure.
have an infection.
have or had heart rhythm problems.
have high blood pressure.
have liver problems, including a history of hepatitis B virus (HBV) infection.
are pregnant or plan to become pregnant. BRUKINSA can harm your unborn baby. If you are able to become pregnant, your healthcare provider may do a pregnancy test before starting treatment with BRUKINSA.

Females should avoid getting pregnant during treatment and for 1 week after the last dose of BRUKINSA. You should use effective birth control (contraception) during treatment and for 1 week after the last dose of BRUKINSA.
Males should avoid getting female partners pregnant during treatment and for 1 week after the last dose of BRUKINSA. You should use effective birth control (contraception) during treatment and for 1 week after the last dose of BRUKINSA.

are breastfeeding or plan to breastfeed. It is not known if BRUKINSA passes into your breast milk. Do not breastfeed during treatment with BRUKINSA and for 2 weeks after the last dose of BRUKINSA.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking BRUKINSA with certain other medications may affect how BRUKINSA works and can cause side effects.

What are the possible side effects of BRUKINSA?

BRUKINSA may cause serious side effects, including:

Bleeding problems (hemorrhage). Bleeding problems are common with BRUKINSA, and can be serious and may lead to death. Your risk of bleeding may increase if you are also taking a blood thinner medicine. Tell your healthcare provider if you have any signs or symptoms of bleeding, including:

blood in your stools or black stools (looks like tar)
pink or brown urine
unexpected bleeding, or bleeding that is severe or you cannot control
vomit blood or vomit that looks like coffee grounds
cough up blood or blood clots
increased bruising
dizziness
weakness
confusion
change in speech
headache that lasts a long time

Infections that can be serious and may lead to death. Tell your healthcare provider right away if you have fever, chills, or flu-like symptoms.
Decrease in blood cell counts (white blood cells, platelets, and red blood cells). Your healthcare provider should do blood tests during treatment with BRUKINSA to check your blood counts.
Second primary cancers. New cancers have happened in people during treatment with BRUKINSA, including cancers of the skin or other organs. Your healthcare provider will check you for other cancers during treatment with BRUKINSA. Use sun protection when you are outside in sunlight.
Heart rhythm problems (atrial fibrillation, atrial flutter, and ventricular arrhythmias) that can be serious and may lead to death. Tell your healthcare provider if you have any of the following signs or symptoms:

your heartbeat is fast or irregular
feel lightheaded or dizzy
pass out (faint)
shortness of breath
chest discomfort

The most common side effects of BRUKINSA include:

decreased white blood cell count
decreased platelet count
upper respiratory tract infection
bleeding
muscle, bone, or joint pain

These are not all the possible side effects of BRUKINSA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is BRUKINSA?

BRUKINSA is a prescription medicine used to treat adults 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 treatment for their cancer.
Marginal zone lymphoma (MZL) when the disease has come back or did not respond to treatment and who have received at least one certain type of treatment.
Follicular lymphoma (FL), in combination with the medicine obinutuzumab, when the disease has come back or did not respond to treatment and who have received at least two prior treatments.

It is not known if BRUKINSA is safe and effective in children.

Please see full Prescribing Information including Patient Information.

References: 1. BRUKINSA. Package insert. BeiGene USA, Inc.; 2023. 2. Data on file. BeiGene USA, Inc. 3. 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. 4. 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. 5. Brown JR, Eichhorst B, Hillmen P, et al. Zanubrutinib demonstrates superior progression-free survival compared with ibrutinib for treatment of relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma: results from final analysis of ALPINE randomized phase 3 study. Presented at: American Society of Hematology (ASH) Annual Meeting and Exposition; December 10-13, 2022. 6. Cull G, Burger JA, Opat S, et al. Zanubrutinib for treatment-naïve and relapsed/refractory chronic lymphocytic leukaemia: long-term follow-up of the phase I/II AU-003 study. Br J Haematol. 2022;196(5):1209-1218.

Want to learn about a different indication?

WM MCL MZL

BRUKINSA for CLL The BRUKINSA Difference

Study Design Efficacy Safety

Rates of hypertension were comparable between BRUKINSA and ibrutinib1