The European Medicines Agency Review of Luspatercept for the Treatment of Adult Patients With Transfusion‐dependent Anemia Caused by Low‐risk Myelodysplastic Syndromes With Ring Sideroblasts or Beta‐thalassemia

• Published in: HemaSphere 2021-08, Vol.5 (8), p.e616-n/a
• Main Authors: Delgado, Julio, Voltz, Caroline, Stain, Milena, Balkowiec‐Iskra, Ewa, Mueller, Brigitte, Wernsperger, Johanna, Malinowska, Iwona, Gisselbrecht, Christian, Enzmann, Harald, Pignatti, Francesco
• Format: Article
• Language: English
• Subjects: Review
• ISSN: 2572-9241; 2572-9241
• DOI: 10.1097/HS9.0000000000000616

Luspatercept is a recombinant fusion protein that selectively binds to ligands belonging to the transforming growth factor‐beta superfamily, resulting in erythroid maturation and differentiation. On June 25, 2020, a marketing authorization valid through the European Union (EU) was issued for luspatercept for the treatment of adult patients with transfusion‐dependent anemia caused by very low‐, low‐, and intermediate‐risk myelodysplastic syndromes (MDS) with ring sideroblasts, or those with transfusion‐dependent beta thalassemia (BT). Luspatercept was evaluated in 2 separate phase 3, double‐blind, placebo‐controlled multicentre trials. The primary endpoints of these trials were the percentage of patients achieving transfusion independence over ≥8 weeks or longer for patients with MDS, and the percentage of patients achieving a ≥33% reduction in transfusion burden from baseline to week 13–24 for patients with BT. In the MDS trial, the percentage of responders was 37.91% versus 13.16%, P < 0.0001, for patients receiving luspatercept versus placebo, respectively. In the BT trial, the percentage of responders was 21.4% versus 4.5% (P < 0.0001) for luspatercept versus placebo, respectively. Treatment with luspatercept led to similar incidences of adverse events (AEs), but higher incidences of grade ≥3 AEs and serious AEs compared to placebo. The most frequently reported treatment‐emergent AEs (≥15%) in the pooled luspatercept group were headache; back pain, bone pain, and arthralgia; diarrhea; fatigue; pyrexia; and cough. The aim of this article is to summarize the scientific review of the application, which led to the regulatory approval in the EU.