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The use of luspatercept for thalassemia in adults.

ABSTRACT: Luspatercept is an activin receptor ligand trap that has been shown to enhance late-stage erythropoiesis in animal models of ?-thalassemia. A multicenter, international, phase 2 dose-finding study was initiated in adult patients with ?-thalassemia, either non-transfusion-dependent thalassemia (NTDT) or transfusion-dependent thalassemia (TDT). Positive results of the phase 2 study paved the way to a randomized phase 3 clinical trial (BELIEVE) to assess the efficacy and safety of luspatercept. The BELIEVE trial is a randomized, double-blind, placebo-controlled phase 3 trial. Three hundred thirty-six patients aged ?18 years with TDT (regularly transfused, 6-20 red blood cell units within 24 weeks before randomization) were included in the trial. Patients received luspatercept or placebo subcutaneously every 21 days for ?48 weeks and best supportive care. Forty-eight of 224 patients (21.4%) in the luspatercept group achieved the primary end points (?33% reduction in transfusion burden) compared with those in the placebo group (4.5%; P < .001). Moreover, more patients had a ?33% reduction in transfusion burden during any rolling 12-week interval (70.5% vs 29.5%) or any 24-week interval (41.1% vs 2.7%) with luspatercept than with the placebo. Transfusion independence was achieved by 11% of patients in the luspatercept group. Transient adverse events were more frequent with luspatercept than with placebo, but were manageable. Luspatercept was approved by the US Food and Drug Administration in 2019 and by the European Medicines Agency in 2020. The luspatercept trial is registered on www.clinicaltrials.gov at #NCT01749540 and the BELIEVE trial at #NCT02604433.

SUBMITTER: Cappellini MD

PROVIDER: S-EPMC7805339 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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The use of luspatercept for thalassemia in adults.

Cappellini Maria Domenica MD Taher Ali T AT

Blood advances 20210101 1

Luspatercept is an activin receptor ligand trap that has been shown to enhance late-stage erythropoiesis in animal models of β-thalassemia. A multicenter, international, phase 2 dose-finding study was initiated in adult patients with β-thalassemia, either non-transfusion-dependent thalassemia (NTDT) or transfusion-dependent thalassemia (TDT). Positive results of the phase 2 study paved the way to a randomized phase 3 clinical trial (BELIEVE) to assess the efficacy and safety of luspatercept. The ...[more]

PMID: 33570654

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Project description:Hemoglobinopathies, including thalassemias and sickle cell disease, are the most common monogenic diseases worldwide, with estimated annual births of more than 330,000 affected infants. Hemoglobin disorders account for about 3.4% of deaths in children under 5 years of age. The distribution of these diseases is historically linked to current or previously malaria-endemic regions; however, immigration has led to a worldwide distribution of these diseases, making them a global health problem. During the last decade, new treatment approaches and novel therapies have been proposed, some of which have the potential to change the natural history of these disorders. Indeed, the first erythroid maturation agent, luspatercept, and gene therapy have been approved for beta-thalassemia adult patients. For sickle cell disease, molecules targeting vaso-occlusion and hemoglobin S polymerization include crizanlizumab, which has been approved for patients ≥ 16 years, voxelotor approved for patients ≥ 12 years, and L-glutamine for patients older than 5 years. Conclusion: We herein present the most recent advances and future perspectives in thalassemia and sickle cell disease treatment, including new drugs, gene therapy, and gene editing, and the current clinical trial status in the pediatric populations. What is Known: • Red blood cell transfusions, iron chelation therapy and hematopoietic stem cell transplantation have been the mainstay of treatment of thalassemia patients for decades. • For sickle cell disease, until 2005, treatment strategies were mostly the same as those for thalassemia, with the option of simple transfusion or exchange transfusion. In 2007, hydroxyurea was approved for patients ≥ 2 years old. What is New: • In 2019, gene therapy with betibeglogene autotemcel (LentiGlobin BB305) was approved for TDT patients ≥ 12 years old non β0/β0 without matched sibling donor. • Starting from 2017 several new drugs, such as L-glutamine (approved only by FDA), crizanlizumab (approved by FDA and EMA for patients ≥ 16 years), and lastly voxelotor (approved by FDA and EMA for patients ≥ 12 years old).

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The use of luspatercept for thalassemia in adults.

Publications

The use of luspatercept for thalassemia in adults.

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