FDA Approves REBLOZYL® (luspatercept-aamt) for the Treatment of Anemia in Adults With Beta Thalassemia Who Require Regular Red Blood Cell Transfusions
REBLOZYL is the first and only
Approval of REBLOZYL marks the first
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“Today’s approval is an important milestone and underscores our continued commitment to patients with hematology disorders,” said
“We’re thrilled that Acceleron’s first approved medicine is one with the potential to help patients with beta thalassemia, who have been in need of new treatments for this lifelong disease,” said
Beta thalassemia is a rare, 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 more severe complications for patients – as well as other serious health issues.2,3 Treatment options for anemia associated with beta thalassemia are limited, consisting mainly of
The approval of REBLOZYL for beta thalassemia, which received a Priority Review designation from the
The study also met key secondary endpoints, including transfusion burden reduction of at least 33% (with a reduction of at least 2 units), during weeks 37 to week 48, which was achieved in 19.6% (n=44) of patients in the REBLOZYL arm and 3.6% (n=4) in the placebo arm (risk difference [95% CI]: 16.1 [9.8, 22.4], P<0.0001).1
Other efficacy endpoints included transfusion burden reduction of ≥50% (with a reduction of at least 2 units) during weeks 13-24 and weeks 37-48.1 A ≥50% reduction in transfusion burden was observed in 7.6% of patients (n=17) receiving REBLOZYL vs. 1.8% of patients (n=2) in the placebo arm at weeks 13-24 (risk difference [95% CI]: 5.8 [1.6, 10.1], P=0.0303), and 10.3% of patients (n=23) vs. 0.9% of patients (n=1) at weeks 37-48 (risk difference [95% CI]: 9.4 [5, 13.7], P=0.0017), respectively.1
In the BELIEVE trial, thromboembolic events, including deep vein thromboses, pulmonary embolus, portal vein thrombosis, and ischemic stroke, were experienced in 3.6% (8/223) of REBLOZYL treated patients.1 Hypertension was reported in 10.7% (61/571) of REBLOZYL-treated patients across the clinical development program.1 REBLOZYL may cause fetal harm when administered to a pregnant woman. Serious adverse reactions occurred in 3.6% of patients receiving REBLOZYL.1 Serious adverse reactions reported in 1% of patients were cerebrovascular accident and deep vein thrombosis.1 One patient died due to an unconfirmed case of AML.1 The 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%).1
Permanent discontinuation due to an adverse reaction (Grades 1-4) occurred in 5.4% of patients who received REBLOZYL.1 The most frequent adverse reactions requiring permanent discontinuation in patients who received REBLOZYL included arthralgia (1%), back pain (1%), bone pain (<1%), and headache (<1%).1 Dosage reductions due to an adverse reaction occurred in 2.7% of patients who received REBLOZYL.1 The most frequent adverse reactions requiring a dosage reduction in >0.5% of patients who received REBLOZYL included hypertension and headache.1 Dosage interruptions due to an adverse reaction occurred in 15.2% of patients who received REBLOZYL.1 The most frequent adverse reactions requiring a dosage interruption in >1% of patients who received REBLOZYL included upper respiratory tract infection, ALT increase, and cough.1
REBLOZYL is anticipated to be available 1 week following the
BELIEVE is a Phase 3, randomized, double-blind, placebo-controlled multicenter study comparing REBLOZYL + best supportive care (BSC) versus placebo + BSC in adults who require regular
REBLOZYL is a first-in-class erythroid maturation agent that promotes late-stage red blood cell maturation in animal models.1
Additional Clinical Investigation
A Phase 2 trial (BEYOND) in adult patients with non-transfusion-dependent beta thalassemia5; a Phase 3 trial (COMMANDS) in ESA-naïve, lower-risk MDS patients6; and a Phase 2 trial in myelofibrosis patients are ongoing.7 For more information, please visit www.clinicaltrials.gov.
REBLOZYL has not been approved as safe and effective for use in patients with MDS or myelofibrosis in any country.
REBLOZYL is indicated for the treatment of anemia in adult patients with beta thalassemia who require regular red blood cell (
REBLOZYL is not indicated for use as a substitute for
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 3-4 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 occurring in 1% of patients included cerebrovascular accident and deep vein thrombosis. A fatal adverse reaction occurred in one patient treated with REBLOZYL who died due to an unconfirmed case of 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%).1
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 for REBLOZYL
Acceleron is a biopharmaceutical company dedicated to the discovery, development, and commercialization of therapeutics to treat serious and rare diseases. The Company'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, neuromuscular, and pulmonary diseases. In hematology, the Company and its global collaboration partner,
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the potential benefits of, and plans relating to the collaboration between Acceleron and
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1 REBLOZYL U.S. Prescribing Information. Accessed
4 Galanello R and Origa R. Beta-thalassemia. Orphanet J Rare Dis. 2010 May 21;5:11. Available at: https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-11. Accessed
5 ClinicalTrials.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
6 ClinicalTrials.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
7 ClinicalTrials.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
Acceleron Pharma Inc.
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