European Commission to Review Luspatercept for Anemia-Associated, Non-Transfusion Dependent Beta Thalassemia

Noah Berkowitz, MD, PhD

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of luspatercept-aamt (Reblozyl) for the treatment of patients with anemia associated with non–transfusion dependent beta thalassemia.¹

The recommendation will now be reviewed by the European Commission, which is expected to announce its final decision within 67 days of receiving the recommendation from CHMP. If approved, this would represent the third approval for luspatercept in the European Union (EU).

The recommendation is based on findings from the pivotal phase 2 BEYOND trial (NCT03342404), which evaluated the efficacy and safety of luspatercept vs placebo in patients with non-transfusion dependent beta thalassemia (n = 145). Results demonstrated 77.1% (n = 74/96) of patients who received luspatercept achieved at least 1.0 g/dL mean hemoglobin (Hb) increase from baseline compared with 0% (n = 0/49) of patients in the placebo arm (P < .0001).²

“Beta thalassemia is an inherited blood disorder that puts patients at significant risk for long-term clinical complications that can impair their quality of life, regardless of whether they require regular blood transfusions,” Noah Berkowitz, ​MD, PhD, senior vice president, Hematology Development, Bristol Myers Squibb, said in a press release.

“Results from the BEYOND study showed [luspatercept] improved anemia associated with non–transfusion dependent beta thalassemia by sustaining hemoglobin increases in 77% of patients regardless of their baseline hemoglobin status. The potential approval of [luspatercept] for patients with non-transfusion-dependent beta thalassemia represents an important development in the EU where several countries present with a high prevalence and where more people are impacted by the disease.”

Luspatercept is an erythroid maturation agent with approved indications in the EU, the United States, China and Canada for anemia-associated, transfusion-dependent beta thalassemia and transfusion-dependent lower-risk myelodysplastic syndromes.

BEYOND was a double-blind, randomized, placebo-controlled, multicenter study that was divided into the screening period, double-blind treatment period (DBTP), open-label phase (OLP), and post-treatment follow-up period (PTFP). Patients were randomly assigned 2:1 to receive luspatercept vs placebo.

All patients were eligible to receive best supportive care, which included red blood cell transfusions; iron-chelating agents; use of antibiotic, antiviral, and antifungal therapy; and/or nutritional support, as needed.

The primary end point of the study was the proportion of patients with an improvement from baseline of at least 1.0 g/dL in their mean hemoglobin values over a continuous 12-week interval from week 13 to week 24 of treatment in the absence of transfusions. Key secondary end points included the mean change in non–transfusion dependent beta thalassemia–patient-reported outcome Tiredness/Weakness domain score and baseline Hb.

In a key secondary end point of the study, 49.0% (n = 47/96) of patients who received luspatercept experienced a mean Hb increase of at least 1.5 g/dL compared with baseline from week 37 to 48 in the absence of transfusions vs 0 patients in the placebo arm. Additionally, 89.6% of patients in the luspatercept arm remained transfusion free at weeks 1 to 24 compared with 67.3% of patients in the placebo arm. Improvements in patient-reported, quality-of-life outcomes were also associated with Hb increases.

Regarding safety, serious adverse effects (AEs) were reported in 11.5% of patients (n = 11) in the luspatercept arm and 25% of patients (n = 24) who received placebo. The most frequent AEs occurring in at least 10% of patients who received luspatercept were 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%).

References

1. Bristol Myers Squibb receives positive CHMP opinion for Reblozyl® (luspatercept) for adult patients with anemia-associated, non-transfusion-dependent (NTD) beta thalassemia. News release. Bristol Myers Squibb. January 27, 2023. Accessed January 27, 2023. https://bit.ly/3XJaMw6
2. 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 Hematol. 2022;9(10):e733-e744. doi:10.1016/S2352-3026(22)00208