New England Journal of Medicine Publishes Results from Pivotal Phase 3 BELIEVE Trial of Reblozyl (luspatercept-aamt) in Adult Patients With Beta Thalassemia
Results demonstrate that treatment with Reblozyl provides significant reduction in transfusion burden for patients with beta thalassemia-associated anemia compared to placebo
“These results published in the
In the BELIEVE trial, a significantly higher proportion of patients achieved a >33% reduction in RBC transfusion burden from baseline (with a reduction of at least two units) during weeks 13-24 when treated with Reblozyl compared to placebo, meeting the study’s primary endpoint. The study also met all key secondary endpoints with a significantly greater proportion of patients receiving Reblozyl compared to placebo achieving a >33% reduction in RBC transfusion burden during weeks 37-48 and a >50% reduction during weeks 13-24 or weeks 37-48.2
The most common adverse events (AEs) of any grade in greater than 5% of the Reblozyl treatment group compared to placebo were bone pain (19.7% vs. 8.3%), arthralgia (19.3% vs. 11.9%), dizziness (11.2% vs. 4.6%), hypertension (8.1% vs. 2.8%) and hyperuricemia (7.2% vs 0%). Grade >3 treatment emergent AEs were reported in a greater proportion of patients receiving Reblozyl compared to placebo (29.1% vs. 15.6%). The most common Grade >3 AEs reported with Reblozyl were anemia (3.1% vs. 0%), increased liver iron concentration (2.7% vs. 0.9%) and hyperuricemia (2.7% vs. 0%) compared to placebo, respectively. Serious adverse events were reported in 15.2% of patients receiving Reblozyl and 5.5% of patients receiving placebo.2
“We could not be more proud that the
Results from BELIEVE supported the
Reblozyl is not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia.
BELIEVE is a Phase 3, randomized, double-blind, placebo-controlled multicenter study comparing REBLOZYL plus best supportive care (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.2 Best supportive care included RBC transfusions; iron-chelating agents; use of antibiotic, antiviral, and antifungal therapy; and/or nutritional support as needed.2
Building upon our transformative work and legacy in hematology and Immuno-Oncology that has changed survival expectations for many cancers, our researchers are advancing a deep and diverse pipeline across multiple modalities. In the field of immune cell therapy, this includes registrational chimeric antigen receptor (CAR) T-cell agents for numerous diseases, and a growing early-stage pipeline that expands cell and gene therapy targets, and technologies. We are developing cancer treatments directed at key biological pathways using our protein homeostasis platform, a research capability that has been the basis of our approved therapies for multiple myeloma and several promising compounds in early to mid-stage development. Our scientists are targeting different immune system pathways to address interactions between tumors, the microenvironment and the immune system to further expand upon the progress we have made and help more patients respond to treatment. Combining these approaches is key to delivering new options for the treatment of cancer and addressing the growing issue of resistance to immunotherapy. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines a reality for patients.
About Reblozyl® (luspatercept-aamt)
Reblozyl is an erythroid maturation agent that promoted late-stage red blood cell maturation in animal models.3
A Biologics License Application for Reblozyl for the treatment of anemia in adults with very low- to intermediate-risk myelodysplastic syndromes (MDS) who have ring sideroblasts (MDS-RS) and who require regular red blood cell transfusions is currently under FDA review with a Prescription Drug User Fee Act (PDUFA), or target action, date of
Additional Clinical Investigation
A Phase 2 trial (BEYOND) in adult patients with non-transfusion-dependent beta thalassemia4; a Phase 2 trial in pediatric patients with transfusion-dependent beta thalassemia5; a Phase 3 trial (COMMANDS) in erythropoiesis-stimulating agent-naïve, lower-risk MDS patients6; and a Phase 2 trial in myelofibrosis patients are ongoing.7 The companies are also planning a Phase 3 trial known as INDEPENDENCE in myelofibrosis in 2020. For more information, please visit www.clinicaltrials.gov.
REBLOZYL is indicated for the treatment of anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions.
REBLOZYL is not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia.
Important Safety Information
WARNINGS AND PRECAUTIONS
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. 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 last 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%).
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 full Prescribing Information for REBLOZYL.
Acceleron is a biopharmaceutical company dedicated to the discovery, development, and commercialization of therapeutics to treat serious and rare diseases. Acceleron’s leadership in the understanding of TGF-beta superfamily biology and protein engineering generates innovative compounds that engage the body's ability to regulate cellular growth and repair.
Acceleron focuses its research and development efforts in hematologic and pulmonary diseases. In hematology, Acceleron and its global collaboration partner,
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1 Galanello R, Origa R. Beta thalassemia.
2 Cappellini, M.D., Phase 3 Study of Luspatercept for B-Thalassemia Requiring Transfusion.
4ClinicalTrials.gov. A Study to Determine the Efficacy and Safety of Luspatercept in Adults With Non Transfusion Dependent Beta (β)-Thalassemia (BEYOND). Available at: https://www.clinicaltrials.gov/ct2/show/NCT03342404?term=BEYOND&cond=Beta-Thalassemia&rank=2. Accessed
5ClinicalTrials.gov. Study of Safety & PK of Luspatercept (ACE-536) in Pediatric Subjects Who Require Regular RBC Transfusions Due to Beta (β)-Thalassemia. Available at: https://clinicaltrials.gov/ct2/show/NCT04143724?term=luspatercept%2C+beta+thalassemia%2C+pediatric&draw=2&rank=1. Accessed
6ClinicalTrials.gov. Efficacy and Safety Study of Luspatercept (ACE-536) Versus Epoetin Alfa for the Treatment of Anemia Due to IPSS-R Very Low, Low or Intermediate Risk Myelodysplastic Syndromes (MDS) in ESA Naïve Subjects Who Require Red Blood Cell Transfusions (COMMANDS). Available at: https://www.clinicaltrials.gov/ct2/show/NCT03682536?term=COMMANDS+luspatercept&rank=1. Accessed
7ClinicalTrials.gov. A Safety and Efficacy Study to Evaluate Luspatercept in Subjects With Myeloproliferative Neoplasm-associated Myelofibrosis Who Have Anemia With and Without Red Blood Cell-transfusion Dependence. Available at: https://www.clinicaltrials.gov/ct2/show/NCT03194542?term=luspatercept&cond=Myelofibrosis&rank=1. Accessed
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