Sotatercept, a soluble activin receptor type 2A IgG-Fc fusion protein for the treatment of anemia and bone loss

Noopur Raje, Sonia Vallet

Research output: Journal article (peer-reviewed)Review article

84 Citations (Scopus)

Abstract

Sotatercept (ACE-011), under development by Acceleron Pharma Inc in collaboration with Celgene Corp, is a chimeric protein containing the extracellular domain of the activin receptor 2A (ACVR2A) fused to the Fc domain of human IgG1. Sotatercept contains the binding site of ACVR2A and interferes with downstream signaling cascades, in particular the SMAD pathway, by sequestering activin. The murine counterpart of sotatercept, referred to as RAP-011, has been extensively evaluated in preclinical studies, in particular in models of cancer- and osteoporosis-related bone loss, and the developing companies envisage that sotatercept may also have potential for the treatment of cancer and cancer-related bone loss. In a phase I clinical trial in postmenopausal females, sotatercept increased hematocrit levels, and, in a phase II trial in patients with multiple myeloma, a trend toward improvement in osteolytic lesions as well as antitumor activity was observed. At the time of publication, phase II trials in patients with anemia were ongoing. Future clinical development will rely on an evaluation of the benefits and complications of sotatercept administration, focusing in particular on suppression of ovarian function and increases in hematocrit levels without a consequent risk of hypertension and thrombosis.

Original languageEnglish
Pages (from-to)586-597
Number of pages12
JournalCurrent opinion in molecular therapeutics
Volume12
Issue number5
Publication statusPublished - Oct 2010
Externally publishedYes

Keywords

  • Activin Receptors, Type II/genetics
  • Anemia/drug therapy
  • Animals
  • Bone Diseases, Metabolic/drug therapy
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Disease Models, Animal
  • Female
  • Humans
  • Immunoglobulin Fc Fragments/genetics
  • Male
  • Mice
  • Randomized Controlled Trials as Topic
  • Recombinant Fusion Proteins/genetics

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery
  • Genetics (clinical)

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