An Expert Report on Recombinant Human Thrombopoietin (DB16364)

Executive Summary

Recombinant Human Thrombopoietin (rhTPO), identified by DrugBank accession number DB16364, is a full-length, glycosylated recombinant protein that is structurally and functionally analogous to the endogenous cytokine thrombopoietin, the principal physiological regulator of platelet production.[1] Produced in a mammalian Chinese hamster ovary (CHO) cell expression system, rhTPO represents a direct replacement therapy designed to address conditions of thrombocytopenia arising from insufficient platelet production or excessive destruction.[1]

The primary mechanism of action involves the binding and activation of the thrombopoietin receptor (c-Mpl) on the surface of hematopoietic stem cells and megakaryocyte progenitor cells. This interaction initiates a cascade of intracellular signaling pathways, most notably the Janus kinase/signal transducer and activator of transcription (JAK/STAT) and mitogen-activated protein kinase (MAPK) pathways. These signals collectively promote the survival, proliferation, differentiation, and maturation of megakaryocytes, culminating in a rapid and effective increase in the number of circulating platelets.[1]

Extensive clinical investigation, predominantly conducted in China, has substantiated the efficacy of rhTPO in various clinical settings. It has demonstrated significant therapeutic benefit in raising platelet counts and mitigating bleeding risk in patients with Primary Immune Thrombocytopenia (ITP), with established efficacy in adult, pediatric, and pregnant populations.[1] Furthermore, rhTPO is effective in the management of Chemotherapy-Induced Thrombocytopenia (CIT).[7] Clinical evidence suggests that dose optimization, particularly the use of higher doses such as 30,000 U/day, can elicit faster and more robust responses in ITP compared to conventional dosing regimens.[4]