FDA Approves Luspatercept to Treat Beta Thalassemia–Associated Anemia

The FDA approved luspatercept-aamt (Reblozyl) to treat anemia in adult patients with beta thalassemia who require regular red blood cell transfusions.^1-2

Moreover, luspatercept is the first and only FDA-approved erythroid maturation agent.

“There are very limited options for patients living with anemia due to beta thalassemia who are dependent on long term red blood cell transfusions. We are pleased to make Reblozyl available as a new therapy for these patients to help address their anemia, a significant clinical complication of beta thalassemia” Nadim Ahmed, president of global hematology and oncology for Celgene, said in a press release.

The agency’s approval was based on results from the pivotal, phase 3, randomized, double-blind, placebo-controlled, multicenter BELIEVE trial – designed to evaluate the safety and efficacy of luspatercept, which works by regulating late-stage red blood cell maturation to help patients reduce their red blood cell transfusion burden, for the treatment of anemia in adult patients with beta thalassemia who require regular red blood cell transfusions.

Patients were randomized 2:1 to receive either luspatercept (n = 224), administered subcutaneously once every 3 weeks as long as a reduction in transfusion requirement was observed or until unacceptable toxicity, or placebo (n = 112).

Regular red blood cell transfusions were defined as 6-20 red blood cell units per 24 weeks, with no transfusion-free period greater than 35 days during that time period.

Reduction from baseline in red blood cell transfusion burden served as the primary endpoint of the study, while secondary endpoints included a transfusion burden reduction of at least 33% (with a reduction of at least 2 units), during weeks 37-48; and a transfusion burden reduction of ≥50% (with a reduction of at least 2 units) during weeks 13-24 and weeks 37-48.

Patients treated with luspatercept experienced a meaningful and statistically significant improvement in the reduction of red blood cell transfusion burden. Overall, 21.4% of patients (n = 48) achieved a ≥33% reduction during weeks 13-24 after randomization of treatment, compared to 4.5% (n = 5) of patients in the placebo arm (risk difference, 17.0; 95% CI, 10.4-23.6; P < .0001).

In addition, 19.6% (n = 44) of patients in the luspatercept arm and 3.6% (n = 4) in the placebo arm experienced a transfusion burden reduction of at least 33% during weeks 37-48 (risk difference, 16.1; 95% CI, 9.8-22.4; P < .0001).

The researchers also observed a ≥50% reduction in transfusion burden in 7.6% of patients (n = 17) who received luspatercept, compared with 1.8% of patients (n = 2) in the placebo arm at weeks 13-24 (risk difference, 5.8; 95% CI, 1.6-10.1; P =.0303); and 10.3% of patients (n = 23), compared with 0.9% of patients (n = 1), respectively, at weeks 37-48 (risk difference, 9.4; 95% CI, 5-13.7; P =.0017).

Thromboembolic events, which occurred in 3.6% of patients treated with luspatercept, included deep vein thromboses, pulmonary embolus, portal vein thrombosis, and ischemic stroke. Serious adverse events (AEs) occurred in 3.6% of patients. One patient died due to an unconfirmed case of acute myeloid leukemia. 

The most common AEs in the luspatercept  and placebo arms were headache (26% vs 24%, respectively), 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 AE occurred in 5.4% of patients who received luspatercept, which included arthralgia (1%), back pain (1%), bone pain (<1%), and headache (<1%), and dose reductions occurred in 2.7% of patients. 

Lastly, Celgene noted that the agent is not indicated for use as a substitute for red blood cell transfusions in patients who require immediate correction of anemia.

The FDA recommended a starting dose of 1 mg/kg once every 3 weeks by subcutaneous injection.

Reference:

1. Celgene. FDA Approves REBLOZYL® (luspatercept-aamt) for the Treatment of Anemia in Adults With Beta Thalassemia Who Require Regular Red Blood Cell Transfusions. Available at: https://ir.celgene.com/press-releases/press-release-details/2019/FDA-Approves-REBLOZYL-luspatercept-aamt-for-the-Treatment-of-Anemia-in-Adults-With-Beta-Thalassemia-Who-Require-Regular-Red-Blood-Cell-Transfusions/default.aspx. Accessed: November 8, 2019.

2. Food and Drug Administration. FDA approves luspatercept-aamt for anemia in patients with beta thalassemia. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-luspatercept-aamt-anemia-patients-beta-thalassemia. Accessed: November 8, 2019.