PATIENT OUTCOMES: REBLOZYL SAFETY

REBLOZYL offers a
demonstrated safety profile for beta thalassemia patients¹

The majority of adverse reactions with REBLOZYL were Grade 1 or 2 (mild to moderate)

Serious adverse reactions occurred in 3.6% of patients on REBLOZYL
Serious adverse reactions reported in 1% of patients were cerebrovascular accident and deep vein thrombosis
A fatal adverse reaction occurred in 1 patient treated with REBLOZYL, who died due to an unconfirmed case of acute myeloid leukemia (AML)

Adverse reactions (>5%) in patients with beta-thalassemia receiving REBLOZYL with a difference between arms of 1% in the BELIEVE trial¹

Body system/ Adverse reaction	REBLOZYL (n=223)		Placebo (n=109)
Body system/ Adverse reaction	All Grades n(%)	Grade 3^a n (%)	All Grades n (%)	Grade ≥3 n (%)
Musculoskeletal and connective tissue disorders Bone pain Arthralgia	44 (20) 43 (19)	3 (1) 0 (0)	9 (8) 13 (12)	0 (0) 0 (0)
Infections and infestations Influenza Viral upper respiratory infection	19 (9) 14 (6)	0 (0) 1 (0.4)	6 (6) 2 (2)	0 (0) 0 (0)
Nervous system disorders Headache Dizziness	58 (26) 25 (11)	1 (<1) 0 (0)	26 (24) 5 (5)	1 (1) 0 (0)
General disorders and administration-site conditions Fatigue	30 (14)	0 (0)	14 (13)	0 (0)
Gastrointestinal discorders Abdominal pain^b Diarrhea Nausea	31 (14) 27 (12) 20 (9)	0 (0) 1 (<1) 0 (0)	13 (12) 11 (10) 6 (6)	0 (0) 0 (0) 0 (0)
Vascular disorders Hypertension^c	18 (8)	4 (2)	3 (3)	0 (0)
Metabolism and nutrition disorders Hyperuricemia	16 (7)	6 (3)	0 (0)	0 (0)
Respiratory, thoracic, and mediastinal disorders Cough	32 (14)	0 (0)	12 (11)	0 (0)

^aLimited to Grade 3 reactions with the exception of 4 events of Grade 4 hyperuricemia. ^bGrouped term includes: Abdominal pain and abdominal pain upper. ^cGrouped term includes: Essential hypertension, hypertension, and hypertensive crisis.

Important considerations while treating patients with REBLOZYL

Liver function abnormalities¹

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Liver function laboratory abnormalities in the BELIEVE trial¹

	REBLOZYL (n=223) n (%)	Placebo (n=109) n (%)
ALT ≥3 x ULN	26 (12)	13 (12)
AST ≥3 x ULN	25 (11)	5 (5)
ALP ≥2 x ULN	17 (8)	1 (<1)
Total bilirubin ≥2 x ULN	143 (64)	51 (47)
Direct bilirubin ≥2 x ULN	13 (6)	4 (4)

Immunogenicity¹

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Extramedullary hematopoietic (EMH) masses

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Lactation¹

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REBLOZYL discontinuations and dose modifications due to adverse reactions in BELIEVE¹

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Additional analyses of adverse events (AEs) by REBLOZYL treatment cycle²:

Newly experienced AEs

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Proportion of patients with newly experienced AEs that occurred in ≥10% of patients and had a ≥5% higher incidence in the REBLOYZL arm vs placebo by treatment cycle*

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Scatter plot depicting the percentage of patients experiencing arthralgia, bone pain, and dizziness over 40 doses of REBLOZYL, showing rates of new cases decreasing over time.

This additional analysis examined the AEs that occurred in ≥10% of patients and had a ≥5% higher incidence in the REBLOZYL arm vs placebo. The AEs that met these requirements included bone pain, arthralgia, and dizziness. The incidence of adverse reactions in the REBLOZYL and placebo arms can be seen in the table above³

Analysis limitations

All patients in both arms were eligible to receive BSC as needed: RBC transfusions; iron-chelating agents; use of antibiotic, antiviral, and antifungal therapy; and nutritional support¹
AEs were analyzed in terms of treatment-emergent adverse events (TEAEs), which were defined as any AEs that occurred or worsened on or after the start of study drug through 63 days after the last dose of the study drug. In addition, any AE with an onset date beyond this time frame and that was assessed by the investigator as related to the study drug was considered a TEAE. If a subject experienced multiple TEAEs under the same system organ class (SOC) or preferred term (PT), then the subject was counted only once for that SOC or PT³

Additional analysis information

The BELIEVE trial captured all TEAEs, including all AEs independent of attribution of treatment or disease³
Patients who crossed over from the placebo arm to the REBLOZYL arm had similar rates of incidence and discontinuation due to these AEs, compared with patients who were initially randomized to the REBLOZYL arm²
“Newly experienced” is defined as first occurrence of indicated TEAE at the given treatment cycle

Bone pain, arthralgia, and dizziness

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Overall incidence and median duration of bone pain, arthralgia, and dizziness^1,4

The incidence of all-grade adverse reactions occurring in ≥10% of patients and ≥5% higher in REBLOZYL vs placebo were bone pain (20% vs 8%, respectively), arthralgia (19% vs 12%), and dizziness (11% vs 5%).^1,4

	Grade 1/2 ADR	Grade ≥3 ADR	Median duration of TEAE
Bone pain	18% (41/223)	1% (3/223)	22.0 days (min, max: 1, 413; n=45/223)
Arthralgia	19% (43/223)	0% (0/223)	15.0 days (min, max: 1, 524; n=47/223)
Dizziness	11% (25/223)	0% (0/223)	6.0 days (min, max: 1, 387; n=27/223)

ADR=adverse drug reaction; ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; BSC=best supportive care; RBC=red blood cell; ULN=upper limit of normal.

Review how to dose REBLOZYL to optimize response

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References: 1. REBLOZYL [US Prescribing Information]. Summit, NJ: Celgene Corporation; 2023. 2. Viprakasit V, Taher AT, Hermine O, et al. Evaluating luspatercept responders in the phase 3, randomized, double-blind, placebo-controlled BELIEVE trial of luspatercept in adult β-thalassemia patients who require regular red blood cell transfusions. Poster presented at: The 61st Annual Meeting of the American Society of Hematology (ASH); December 7-10, 2019. Orlando, FL, USA. 3. Data on file. Celgene Corporation. Summit, New Jersey. 4. Cappellini MD, Viprakasit V, Taher AT, et al. A phase 3 trial of luspatercept in patients with transfusion-dependent β-thalassemia. N Engl J Med. 2020;382(13):1219-1231.

INDICATIONS

REBLOZYL offers a
demonstrated safety profile for beta thalassemia patients¹

Adverse reactions (>5%) in patients with beta-thalassemia receiving REBLOZYL with a difference between arms of 1% in the BELIEVE trial¹

Body system/
Adverse
reaction

REBLOZYL

Placebo

Important considerations while treating patients with REBLOZYL

Liver function abnormalities¹

REBLOZYL
(n=223)
n (%)

Placebo
(n=109)
n (%)

Immunogenicity¹

Extramedullary hematopoietic (EMH) masses

Lactation¹

REBLOZYL discontinuations and dose modifications due to adverse reactions in BELIEVE¹

Permanent discontinuations due to an adverse reaction (Grade 1-4)

Dose reductions due to adverse reaction

Dose interruptions due to an adverse reaction

Additional analyses of adverse events (AEs) by REBLOZYL treatment cycle²:

Newly experienced AEs

Bone pain, arthralgia, and dizziness

Grade 1/2 ADR

Grade ≥3 ADR

Median duration of TEAE

Review how to dose REBLOZYL to optimize response

IMPORTANT SAFETY
INFORMATION

WARNINGS AND PRECAUTIONS

INDICATIONS

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

ADVERSE REACTIONS

LACTATION

DRUG ABUSE POTENTIAL

INDICATIONS

REBLOZYL offers a demonstrated safety profile for beta thalassemia patients1

Adverse reactions (>5%) in patients with beta-thalassemia receiving REBLOZYL with a difference between arms of 1% in the BELIEVE trial1

Body system/ Adverse reaction

REBLOZYL

Placebo

Important considerations while treating patients with REBLOZYL

Liver function abnormalities1

Immunogenicity1

Extramedullary hematopoietic (EMH) masses

Lactation1

REBLOZYL discontinuations and dose modifications due to adverse reactions in BELIEVE1

Additional analyses of adverse events (AEs) by REBLOZYL treatment cycle2:

Newly experienced AEs

Bone pain, arthralgia, and dizziness

Review how to dose REBLOZYL to optimize response

REBLOZYL offers a
demonstrated safety profile for beta thalassemia patients¹

Adverse reactions (>5%) in patients with beta-thalassemia receiving REBLOZYL with a difference between arms of 1% in the BELIEVE trial¹

Body system/
Adverse
reaction

Liver function abnormalities¹

Immunogenicity¹

Lactation¹

REBLOZYL discontinuations and dose modifications due to adverse reactions in BELIEVE¹

Additional analyses of adverse events (AEs) by REBLOZYL treatment cycle²: