The European Commission has granted a full marketing authorization to luspatercept-aamt for use in adult patients with anemia associated with non–transfusion-dependent β-thalassemia.
The European Commission has granted a full marketing authorization to luspatercept-aamt (Reblozyl) for use in adult patients with anemia associated with non–transfusion-dependent (NTD) β-thalassemia.1
The approval was based on findings from the phase 2 BEYOND trial (NCT03342404), which demonstrated that 77.1% of patients treated with luspatercept (n = 74/96) experienced a mean hemoglobin (Hb) increase of 1.0 g/dL or higher from baseline over a continuous 12-week interval from week 13 to week 24 of treatment in the absence of red blood cell (RBC) transfusions compared with 0% of patients (n = 0/49) treated with placebo (P < .0001), meeting the primary end point of the trial.
“β-thalassemia is an inherited blood disorder that puts patients at significant risk for long-term clinical complications due to anemia, leaving a substantial need for treatment options, regardless of a patient’s dependence on blood transfusions. This announcement is welcome news for patients with non-transfusion-dependent beta thalassemia associated anemia across the EU who are seeking newer treatment options to reduce these burdens,” Noah Berkowitz, MD, PhD, senior vice president of Hematology Development at Bristol Myers Squibb, stated in a news release. “Today’s approval represents the third indication for [luspatercept] in Europe, and we look forward to continuing to evaluate this first-in-class therapeutic option across multiple diseases impacted by the burden of anemia in a broad clinical development program.”
Previously, in November 2019, the FDA approved luspatercept for the treatment of anemia in adult patients with β-thalassemia who require regular RBC transfusions.2 In April 2020, the agent was also greenlit in the United States for the treatment of anemia failing an erythropoiesis-stimulating agent and requiring 2 or more RBC units over 8 weeks in adult patients with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis.3
In December 2021, the FDA granted priority review to the supplemental biologics license application (sBLA) seeking the approval of luspatercept for the treatment of anemia in adults with NTD β-thalassemia.4 However, in June 2022, Bristol Myers Squibb withdrew the sBLA after the regulatory agency extended the review period, with the company saying it could not adequately address questions that had been posed by the FDA related to the benefit-risk profile of luspatercept in this population based on the dataset currently available from BEYOND.5,6
The double-blind, randomized, placebo-controlled, multicenter BEYOND study evaluated the safety and efficacy of luspatercept vs placebo in adult patients with NTD β-thalassemia.
Patients were randomly assigned 2:1 to receive luspatercept starting at 1.0 mg/kg that could be escalated up to 1.25 mg/kg once every 3 weeks, or subcutaneous placebo every 3 weeks.7 Patients were eligible to receive best supportive care, including RBC transfusions and iron-chelating agents.1
Key secondary end points included proportion of patients who remained free of transfusion over weeks 1 through 24, those who achieved a mean Hb increase of 1.5 g/dL or higher from baseline to weeks 13 through 24, and a mean change in non–transfusion dependent β-thalassemia patient-reported outcome tiredness and weakness (NTDT-PRO T/W) domain scores.
Additional data showed that 49.0% of patients treated with luspatercept achieved a mean Hb increase of 1.5 g/dL or higher compared with baseline from week 37 to week 48 in the absence of transfusions vs no patients in the placebo arm (P < .0001). Furthermore, 89.6% of patients in the luspatercept arm remained transfusion free at weeks 1 to 24 vs 67.3% of those in the placebo arm (P = .0013).
NTDT-PRO data showed that quality-of-life outcomes regarding tiredness and weakness were also observed to correlate with Hb increases.
Regarding safety, serious adverse effects occurred in 11.5% of patients who received luspatercept. The most common AEs reported in at least 10% of patients in the luspatercept arm included bone pain (36%), headache (30%), arthralgia (29%), back pain (28%), prehypertension (23%), hypertension (20%), cough (18%), diarrhea (17%), influenza-like illness (17%), asthenia (13%), influenza (13%), insomnia (11%), and nausea (10%).