Thrombosis/Thromboembolism

In adult patients with beta thalassemia, thromboembolic events (TEE) were reported in 8/223 (3.6%) REBLOZYL-treated patients. TEEs included deep vein thrombosis, pulmonary embolus, portal vein thrombosis, and ischemic stroke. Patients with known risk factors for thromboembolism (splenectomy or concomitant use of hormone replacement therapy) may be at further increased risk of thromboembolic conditions. Consider thromboprophylaxis in patients at increased risk of TEE. Monitor patients for signs and symptoms of thromboembolic events and institute treatment promptly.

Hypertension

Hypertension was reported in 10.7% (61/571) of REBLOZYL-treated patients. Across clinical studies, the incidence of Grade 3 to 4 hypertension ranged from 1.8% to 8.6%. In adult patients with MDS with normal baseline blood pressure, 26 (29.9%) patients developed SBP ≥130 mm Hg and 23 (16.4%) patients developed DBP ≥80 mm Hg. Monitor blood pressure prior to each administration. Manage new or exacerbations of preexisting hypertension using anti-hypertensive agents.

Embryo-Fetal Toxicity

REBLOZYL may cause fetal harm when administered to a pregnant woman. REBLOZYL caused increased post-implantation loss, decreased litter size, and an increased incidence of skeletal variations in pregnant rat and rabbit studies. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 3 months after the final dose.

• The median time on treatment with REBLOZYL was 50.4 weeks (range, 3–221 weeks)¹
• 67% of patients were exposed for 6 months or longer and 49% were exposed for >1 year¹
• Among the 242 patients treated with REBLOZYL, 5 (2.1%) had a fatal adverse reaction¹
• Selected laboratory abnormalities that changed from Grade 0 to 1 at baseline to Grade ≥2 at any time during the studies in at least 10% of patients included creatinine clearance decreased, total bilirubin increased, and alanine aminotransferase increased¹
• Other clinically relevant adverse reactions reported in <5% of patients included bronchitis, urinary tract infection, and hypertension¹

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

Adverse reactions (≥5%) in patients receiving REBLOZYL with a difference between arms of >2% in MEDALIST trial through cycle 8¹

Selected Grades 2 to 4 treatment-emergent laboratory abnormalities through cycle 8 in the MEDALIST trial¹

Immunogenicity¹

• Of 260 patients with MDS who were treated with REBLOZYL and evaluable for the presence of anti-luspatercept-aamt antibodies, 23 patients (8.9%) tested positive for treatment-emergent anti-luspatercept-aamt antibodies, including 9 patients (3.5%) who had neutralizing antibodies
• Luspatercept-aamt serum concentration tended to decrease in the presence of neutralizing antibodies
• There were no severe acute systemic hypersensitivity reactions reported for patients with anti-luspatercept-aamt antibodies in REBLOZYL clinical trials, and there was no association between hypersensitivity type reaction or injection site reaction and presence of anti‑luspatercept‑aamt antibodies

Additional analysis of treatment-emergent adverse events (TEAEs) by REBLOZYL treatment cycle²

TEAEs ≥5% incidence by treatment cycle

Analysis limitations

• All patients in both arms were eligible to receive BSC, which included RBC transfusions as needed¹
• Adverse events (AEs) with a duration overlapping multiple cycles were only counted in the first overlapped cycle. If an AE occurred multiple times in different cycles, it was counted once in each cycle. If an AE occurred multiple times within the same cycle, it was counted only once. If a patient experienced multiple events under the same MedDRA 20.0 preferred term, then the patient was counted only once for the preferred term²
• Patients who met the criteria and remained on double-blind treatment after completion of week 25 assessment may have continued dosing in the extension phase of the treatment period until the subject experienced unacceptable toxicities, disease progression, withdrew consent, or met any other discontinuation criteria^1,2
• Fatigue TEAE does not include broader asthenic conditions adverse drug reactions (ADRs)

Additional analysis information

• Analysis is based on data through week 48³
• The chart displays TEAEs independent of attribution of treatment or disease. The percentage shown in this graph does not match the Adverse Reactions table above
• TEAEs are undesirable events not present prior to medical treatment, or an already present event that worsens either in intensity or frequency following the treatment