Most frequently reported adverse drug reactions in at least 15% of patients receiving Reblozyl¹

Headache

Bone pain

Arthralgia

The most commonly reported Grade 3 or higher adverse drug reaction was hyperuricemia The most serious adverse reactions reported included thromboembolic events of deep vein thrombosis, ischemic stroke, portal vein thrombosis, and pulmonary embolism.¹

ADVERSE DRUG REACTIONS OBSERVED/REPORTED IN PATIENTS TREATED WITH REBLOZYL1
SYSTEM ORGAN CLASS PREFERRED TERM	FREQUENCY (ALL GRADES)a
Infections and infestations
Bronchitis	Common
Urinary tract infection	Common
Upper respiratory tract infection	Very common
Influenza	Common
Immune system disorders
Hypersensitivityb	Common
Metabolism and nutrition disorders
Hyperuricemia	Common
Nervous system disorders
Dizziness	Very common
Headache	Very common
Syncope/presyncope	Common
Ear and labyrinth disorders
Vertigo/vertigo positional	Common
Vascular disorders
Hypertensionc	Common
Thromboembolic eventsd	Common
Respiratory, thoracic and mediastinal disorders
Dyspnea	Common
Gastrointestinal disorders
Diarrhea	Very common
Nausea	Common
Musculoskeletal and connective tissue disorders
Back pain	Very common
Arthralgia	Very common
Bone pain	Very common
General disorders and administration site conditions
Fatigue	Very common
Asthenia	Common
Injection site reactionse	Common

^a Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000) and very rare (<1/10,000).¹

^bHypersensitivity includes eyelid edema, drug hypersensitivity, swelling face, periorbital edema, face edema, angioedema, lip swelling, and drug eruption.¹

^cHypertension reaction includes essential hypertension, hypertension, and hypertensive crisis.¹

^d Thromboembolic events include deep vein thrombosis, portal vein thrombosis, ischemic stroke, and pulmonary embolism.¹

^eInjection site reactions include injection site erythema, injection site pruritus, injection site swelling, and injection site rash.¹

Selected adverse reactions across MEDALIST and BELIEVE trials¹

Bone Pain

19.7% Reblozyl

8.3% Placebo

Bone pain: Bone pain was reported in 19.7% of patients with β-thalassemia treated with Reblozyl (placebo 8.3%) and in 2.6% of patients with MDS treated with Reblozyl (placebo 3.9%). In patients with β-thalassemia treated with Reblozyl, bone pain was most common in the first 3 months (16.6%) compared to months 4-6 (3.7%). Most events (41/44 events) were Grade 1-2, with 3 events Grade 3. One of the 44 events was serious, and 1 event led to treatment discontinuation.¹

Arthralgia

19.3% Reblozyl

11.9% Placebo

Arthralgia: Arthralgia was reported in 19.3% of patients with ß-thalassemia treated with Reblozyl (placebo 11.9%) and in 5.2% of patients with MDS treated with Reblozyl (placebo 11.8%). In the patients with β-thalassemia treated with Reblozyl, arthralgia led to treatment discontinuation in 2 patients (0.9%).¹

Hypertension

8.1% Reblozyl

2.8% Placebo

Hypertension: Patients treated with Reblozyl had an average increase in systolic and diastolic blood pressure of 5 mm Hg from baseline not observed in patients receiving placebo. Hypertension was reported in 8.5% of patients with MDS (placebo 9.2%) and in 8.1% of patients with β-thalassemia (placebo 2.8%).¹

• In patients with MDS, Grade 3 events were reported for 5 patients (3.3%) treated with Reblozyl and in 3 patients (3.9%) receiving placebo. No patient discontinued due to hypertension.¹

• In patients with β-thalassemia, Grade 3 events were reported in 4 patients (1.8%) treated with Reblozyl (0.0% placebo). No patient discontinued due to hypertension¹

Hypersensitivity

4.5% Reblozyl

1.8% Placebo

Hypersensitivity: Hypersensitivity-type reactions (including eyelid edema, drug hypersensitivity, swelling face, periorbital edema, face edema, angioedema, lip swelling, drug eruption) were reported in 4.6% of patients with MDS (2.6% placebo) and 4.5% of patients with β-thalassemia treated with Reblozyl (1.8% placebo). In clinical studies, all events were Grade 1/2. In patients with β-thalassemia treated with Reblozyl, hypersensitivity led to treatment discontinuation in 1 patient (0.4%).¹

Thromboembolic events (TEEs)

3.6% Reblozyl

0.9% Placebo

Thromboembolic events (including deep vein thrombosis, portal vein thrombosis, ischemic stroke, and pulmonary embolism) occurred in 3.6% of patients with β-thalassemia receiving Reblozyl (placebo 0.9%). All events were reported in patients who had undergone splenectomy and had at least 1 other risk factor. No difference in TEEs was observed between Reblozyl and placebo arms in MDS patients.¹

Injection site reactions

2.2% Reblozyl

1.8% Placebo

Injection site reactions: Injection site reactions (including injection site erythema, injection site pruritus, injection site swelling, and injection site rash) were reported in 3.9% of patients with MDS (placebo 0.0%) and in 2.2% of patients with β-thalassemia receiving Reblozyl (placebo 1.8%). In clinical studies, all events were Grade 1 and none led to discontinuation.¹

Immunogenicity

1.4% of Reblozyl patients
tested positive for
treatment-emergent
anti-luspatercept antibodies

In clinical studies of MDS, an analysis of 260 patients who were treated with Reblozyl and who were evaluable for the presence of anti-luspatercept antibodies, 23 (8.8%) patients tested positive for treatment‑emergent anti-luspatercept antibodies, including 9 (3.5%) patients who had neutralizing antibodies against Reblozyl.¹

In clinical studies of β-thalassemia, an analysis of 284 patients who were treated with Reblozyl and who were evaluable for the presence of anti-luspatercept antibodies, 4 (1.4%) of patients tested positive for treatment-emergent anti-luspatercept antibodies, including 2 (0.7%) of patients who had neutralizing antibodies against Reblozyl.¹

• Luspatercept serum concentration tended to decrease in the presence of neutralizing antibodies. There were no severe systemic hypersensitivity reactions reported for patients with anti-luspatercept antibodies. There was no association between hypersensitivity type reactions or injection site reactions and presence of anti-luspatercept antibodies.¹

of β-thalassemia patients treated with Reblozyl discontinued treatment due to an adverse reaction¹

Adverse reactions leading to study drug discontinuation in the Reblozyl treatment arm were arthralgia, back pain, bone pain, and headache.¹