According to the results of a study published in Lancet Haematology, luspatercept appears to be safe and efficacious in patients with non-transfusion-dependent beta-thalassemia, representing a potential treatment for this high-risk patient population with few available options.
“No drugs are specifically approved for anaemia management in patients with non-transfusion-dependent [beta]-thalassaemia, other than transfusion therapy administered infrequently in accordance with patients’ needs,” the investigators of the BEYOND study wrote in their report (ClinicalTrials.gov Identifier: NCT03342404).
The team conducted a phase 2 randomized, double-blind, multicenter, placebo-controlled trial at 12 centers across 6 countries to evaluate the efficacy and safety of luspatercept compared with placebo in adult patients with non-transfusion-dependent beta-thalassemia.
Patients (≥18 years of age), all of whom were non-transfusion-dependent, were required to have a confirmed diagnosis of beta-thalassemia or hemoglobin E/β-thalassemia, and a baseline hemoglobin concentration of 10.0 g/dL or lower. They were randomly assigned (2:1) to receive luspatercept (up to 1.25 mg/kg, once subcutaneously every 3 weeks, for 48 weeks) or placebo and stratified according to baseline hemoglobin concentration (≥8.5 g/dL vs <8.5 g/dL) and baseline Non-Transfusion-Dependent Beta-thalassaemia-Patient-Reported Outcome Tiredness/Weakness domain score (≥3 vs <3).
The primary endpoint of BEYOND was achievement of an increase from baseline of 1.0 g/dL or higher in mean hemoglobin concentration over a continuous 12-week interval in the absence of transfusions. The reported efficacy and safety analyses were conducted in the intention-to-treat population, and the study remains ongoing.
A total of 145 patients (female, 57%; male, 43%) participated in the study, with 96 in the luspatercept arm and 49 in the placebo arm. Most (60%) patients were White, while the remaining patients identified as Asian (30%) or another race (10%).
The investigators reported that BEYOND met its primary endpoint, with 77% of patients in the luspatercept arm and 0% of those in the placebo arm achieving an increase of at least 1.0 g/dL in hemoglobin concentration (common risk difference, 77.1; 95% confidence interval, 68.7-85.5; P <.0001).
The team also reported that the proportion of patients experiencing serious adverse events was lower in the luspatercept arm than in the placebo arm (12% vs 25%). The most commonly reported treatment-emergent adverse events with luspatercept were bone pain (37%), headache (30%), and arthralgia (29%).
“[T]o our knowledge, this is the first time that the efficacy and safety of luspatercept have been evaluated in a randomized, placebo-controlled trial of patients with non-transfusion-dependent β-thalassemia,” concluded the researchers. “[The] findings might lead to the incorporation of luspatercept in clinical treatment algorithms to guide the management of patients with anemia due to non-transfusion-dependent [beta]-thalassemia.”
Limitations of the study included failure of 1 site to recruit patients and limited ability to make definitive statements of effect from the phase 2 trial.
Disclosure: This research was supported by Celgene and Acceleron Pharma. Please see the original reference for a full list of disclosures.
Taher AT, Cappellini MD, Kattamis A, et al. Luspatercept for the treatment of anaemia in non-transfusion-dependent β-thalassaemia (BEYOND): a phase 2, randomised, double-blind, multicentre, placebo-controlled trial. Lancet Haematol. Published online August 22, 2022. doi:10.1016/S2352-3026(22)00208-3