An Efficacy and Safety Study of Luspatercept (ACE-536) Versus Placebo in Subjects With Myeloproliferative Neoplasm-Associated Myelofibrosis on Concomitant JAK2 Inhibitor Therapy and Who Require Red Blood Cell Transfusions
Key claim: A Phase 3 study is evaluating whether luspatercept versus placebo improves anemia and reduces RBC transfusion need in MPN-associated myelofibrosis patients on concomitant JAK2 inhibitor therapy.
Abstract
The purpose of this Phase 3 study is to evaluate the efficacy and safety of Luspatercept compared with placebo in subjects with myeloproliferative neoplasm (MPN)-associated Myelofibrosis (MF) and anemia on concomitant Janus kinase 2 (JAK2) inhibitor therapy and who require red blood cell count (RBC) transfusions.
The study is divided into Screening Period, a Treatment Phase (consisting of a Blinded Core Treatment Period, a Day 169 Response Assessment, a Blinded Extension Treatment Period, and an Open-label Extension Treatment Period), and a Posttreatment Follow-up Period.
Following the Day 169 Response Assessment, subjects who did not show clinical benefit will have the option to unblind. Subjects who were on placebo during the Blinded Core Treatment Period will have the opportunity to crossover into the Open-Label Extension Treatment Period and receive Luspatercept.
Why this matters
Anemia is a dose-limiting toxicity of JAK inhibitor therapy in myelofibrosis and a major driver of transfusion dependence, yet no approved agent directly addresses this on-treatment anemia. A Phase 3 trial of luspatercept — already approved for MDS and β-thalassemia anemia — would establish the first ligand-trap therapy in the MF armamentarium if positive, and provides a late-stage benchmark against which competing agents (elritercept, sapablursen, nelfinavir, INCB000928) will be measured.