European Commission Approves Reblozyl (luspatercept) for the Treatment of Transfusion-Dependent Anemia in Adult Patients with Myelodysplastic Syndromes or Beta Thalassemia
Reblozyl regulates late-stage red blood cell (RBC) maturation to potentially reduce or eliminate the need for regular RBC transfusions
Reblozyl is the first and only erythroid maturation agent to be approved in the
- Adult patients with transfusion-dependent anemia due to very low-, low- and intermediate-risk myelodysplastic syndromes (MDS) with ring sideroblasts, who had an unsatisfactory response or are ineligible for erythropoietin-based therapy.
- Adult patients with transfusion-dependent anemia associated with beta thalassemia.
"Dependence on blood transfusions caused by anemia in hematologic malignancies like MDS can often mean frequent and lengthy hospital visits, which can pose additional health risks and affect patients’ quality of life,” said
“While beta thalassemia remains an orphan disease, the lifelong blood transfusions often needed by patients can have a significant impact on the limited blood supply in their communities, and there are few treatment alternatives,” said
Reblozyl is the first and only erythroid maturation agent approved in the
“Across the EU, 25 million blood transfusions occur every year, some of which are needed by patients with anemia due to hematologic diseases like MDS and beta thalassemia,” said
MEDALIST is a Phase 3, randomized, double-blind, placebo-controlled, multi-center study evaluating the safety and efficacy of Reblozyl plus best supportive care (BSC) versus placebo plus BSC in adults with IPSS-R-defined very low-, low- or intermediate-risk non-del(5q) MDS. All patients were RBC transfusion-dependent and were either refractory or intolerant to prior erythropoiesis stimulating agent (ESA) therapy, or were
The trial showed a statistically significant improvement in RBC transfusion burden with Reblozyl, the study’s primary endpoint, with 37.9% of patients treated with Reblozyl achieving independence from RBC transfusions for at least eight weeks during the first 24 weeks of the trial compared to 13.2% of patients on placebo. The trial also met the secondary endpoint of transfusion independence for at least 12 weeks within the first 24 and 48 weeks of the study, which was achieved in a significantly greater proportion of patients receiving Reblozyl versus placebo.
The majority of treatment-emergent adverse events (TEAEs) were Grade 1-2. Grade 3 or 4 TEAEs were reported in 42.5% of patients who received Reblozyl and 44.7% of patients who received placebo. Discontinuation due to an adverse reaction (Grades 1-4) occurred in 4.5% of patients who received Reblozyl. The most common (>10%) all-grade adverse reactions included fatigue, musculoskeletal pain, dizziness, diarrhea, nausea, hypersensitivity reactions, hypertension, headache, upper respiratory tract infection, bronchitis and urinary tract infection.
Results of the MEDALIST trial were first presented during the Plenary Session of the
MDS are a group of hematologic malignancies characterized by ineffective production of healthy red blood cells, white blood cells and platelets, which can lead to anemia and frequent or severe infections, and can progress to Acute Myeloid Leukemia (AML). People with MDS who develop anemia often require regular blood transfusions to increase the number of healthy red blood cells in circulation. Frequent transfusions are associated with an increased risk of transfusion reactions, infections and iron overload. There are approximately 50,000 patients with MDS in the EU5 countries (
BELIEVE is a Phase 3, randomized, double-blind, placebo-controlled multi-center study comparing Reblozyl plus BSC versus placebo plus BSC in adults who require regular RBC transfusions (6-20 RBC units per 24 weeks with no transfusion-free period greater than 35 days during that period) due to beta thalassemia.
The trial showed a statistically significant improvement in RBC transfusion burden during weeks 13 to 24 compared to the baseline 12-week interval prior to randomization (21.4% Reblozyl versus 4.5% placebo), meeting the study’s primary endpoint. The trial also met the secondary endpoint of transfusion burden reduction of at least 33% (with a reduction of at least two units) during weeks 37 to 48, which was achieved in a significantly greater proportion of patients receiving Reblozyl versus placebo. The trial also met an exploratory endpoint, with 70.5% of patients treated with Reblozyl achieving at least a 33% reduction in RBC transfusion burden of at least two units for any 12 consecutive weeks compared to the 12-week interval prior to treatment, compared to 29.5% of patients on placebo.
The majority of TEAEs were Grade 1-2. Discontinuation due to an adverse reaction (Grades 1-4) occurred in 5.4% of patients who received Reblozyl. The most common adverse reactions (>10%) were headache, bone pain, arthralgia, fatigue, cough, abdominal pain, diarrhea and dizziness.
Results of the BELIEVE trial were first presented at the ASH Annual Meeting in
About Beta Thalassemia
Beta thalassemia is an inherited blood disorder caused by a genetic defect in hemoglobin. The disease is associated with ineffective erythropoiesis, which results in the production of fewer and less healthy RBCs, often leading to severe anemia—a condition that can be debilitating and can lead to other complications for patients—as well as other serious health issues. Treatment options for anemia associated with beta thalassemia are limited, consisting mainly of frequent RBC transfusions that have the potential to contribute to iron overload, which can cause serious complications such as organ damage. Across
Reblozyl (luspatercept-aamt), a first-in-class erythroid maturation agent, promotes late-stage red blood cell maturation in animal models.
- anemia in adult patients with beta thalassemia who require regular red blood cell transfusions, and
- anemia failing an erythropoiesis stimulating agent and requiring 2 or more red blood cell units over 8 weeks in adult patients with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T).
Reblozyl is not indicated for use as a substitute for red blood cell transfusions in patients who require immediate correction of anemia.
WARNINGS AND PRECAUTIONS
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 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 patients with beta thalassemia with normal baseline blood pressure, 13 (6.2%) patients developed systolic blood pressure (SBP) ≥130 mm Hg and 33 (16.6%) patients developed diastolic blood pressure (DBP) ≥80 mm Hg. 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.
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.
- Serious adverse reactions occurred in 3.6% of patients on REBLOZYL. Serious adverse reactions occurring in 1% of patients included 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)
- Most common adverse reactions (at least 10% for REBLOZYL and 1% more than placebo) were headache (26% vs 24%), bone pain (20% vs 8%), arthralgia (19% vs 12%), fatigue (14% vs 13%), cough (14% vs 11%), abdominal pain (14% vs 12%), diarrhea (12% vs 10%) and dizziness (11% vs 5%)
- Grade >3 (≥2%) adverse reactions included fatigue, hypertension, syncope and musculoskeletal pain. A fatal adverse reaction occurred in 5 (2.1%) patients
- The most common (≥10%) adverse reactions included fatigue, musculoskeletal pain, dizziness, diarrhea, nausea, hypersensitivity reactions, hypertension, headache, upper respiratory tract infection, bronchitis, and urinary tract infection
It is not known whether REBLOZYL is excreted into human milk or absorbed systemically after ingestion by a nursing infant. REBLOZYL was detected in milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because many drugs are excreted in human milk, and because of the unknown effects of REBLOZYL in infants, a decision should be made whether to discontinue nursing or to discontinue treatment. Because of the potential for serious adverse reactions in the breastfed child, breastfeeding is not recommended during treatment and for 3 months after the last dose.
Please see full Prescribing Information and Summary of Product Characteristics for REBLOZYL
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