Development of Romiplostim: A Novel Engineered Peptibody

Thrombopoietin (TPO) is a growth factor that stimulates megakaryocytes to increases platelet counts. Due to concerns around the development of autoantibodies in clinical studies of TPO, a novel peptide that bound the TPO receptor was used to develop a TPO mimetic. This peptide has no shared homology with TPO, and therefore avoids the risk of development of antibodies that cross-react with endogenous TPO. The ability of the artificial peptide to bind and stimulate the TPO receptor was improved by dimerization of the peptide, and the stability of the peptide was improved by linking the peptides to the Fc portion of an antibody. Romiplostim (Nplate, Amgen, Inc, Thousand Oaks, CA) is the first fully engineered fusion of a novel peptide and antibody or “peptibody” that can stimulate platelet production.