Celgene Corporation and Acceleron Pharma Inc. announced the U.S. Food and Drug Administration (FDA) has approved REBLOZYL® (luspatercept-aamt) 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. REBLOZYL is the first and only FDA-approved erythroid maturation agent, representing a new class of therapy which works by regulating late-stage red blood cell maturation to help patients reduce their RBC transfusion burden.

The approval of REBLOZYL for beta thalassemia, which received a Priority Review designation from the FDA, is based on results from the pivotal, Phase 3, randomized, double-blind, placebo-controlled, multicenter BELIEVE trial evaluating the safety and efficacy of REBLOZYL for the treatment of anemia in adult patients with beta thalassemia who require regular RBC transfusions (defined as 6-20 RBC units per 24 weeks, with no transfusion-free period greater than 35 days during that period).1 All patients were eligible to receive best supportive care, which included RBC transfusions; iron-chelating agents; use of antibiotic, antiviral, and antifungal therapy; and/or nutritional support, as needed. The trial achieved a clinically meaningful and statistically significant improvement in the primary endpoint. In the REBLOZYL arm, 21.4% of patients (n=48) achieved a =33% reduction from baseline in RBC transfusion burden (with a reduction of at least 2 units) during weeks 13–24 after randomization, compared to 4.5% (n=5) in the placebo arm (risk difference [95% CI]: 17.0 [10.4, 23.6], P<0.0001).

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). 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. 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. Hypertension was reported in 10.7% (61/571) of REBLOZYL-treated patients across the clinical development program.

REBLOZYL may cause fetal harm when administered to a pregnant woman. Serious adverse reactions occurred in 3.6% of patients receiving REBLOZYL. 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.

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%). Permanent discontinuation due to an adverse reaction (Grades 1-4) occurred in 5.4% of patients who received REBLOZYL. 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%).

Dosage reductions due to an adverse reaction occurred in 2.7% of patients who received REBLOZYL. The most frequent adverse reactions requiring a dosage reduction in >0.5% of patients who received REBLOZYL included hypertension and headache. Dosage interruptions due to an adverse reaction occurred in 15.2% of patients who received REBLOZYL.

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. REBLOZYL is anticipated to be available 1 week following the FDA approval.