A Review of Romiplostim Mechanism of Action and Clinical Applicability

Abstract

Thrombocytopenia results from a variety of conditions, including radiation, chemotherapy, autoimmune disease, bone marrow disorders, pathologic conditions associated with surgical procedures, hematopoietic stem cell transplant (HSCT), and hematologic disorders associated with severe aplastic anemia. Immune thrombocytopenia (ITP) is caused by immune reactions that accelerate destruction and reduce production of platelets. Thrombopoietin (TPO) is a critical component of platelet production pathways, and TPO receptor agonists (TPO-RAs) are important for the management of ITP by increasing platelet production and reducing the need for other treatments. Romiplostim is a TPO-RA approved for use in patients with ITP in the United States, European Union, Australia, and several countries in Africa and Asia, as well as for use in patients with refractory aplastic anemia in Japan and Korea. Romiplostim binds to and activates the TPO receptor on megakaryocyte precursors, thus promoting cell proliferation and viability, resulting in increased platelet production. Through this mechanism, romiplostim reduces the need for other treatments and decreases bleeding events in patients with thrombocytopenia. In addition to its efficacy in ITP, studies have shown that romiplostim is effective in improving platelet counts in various settings, thereby highlighting the versatility of romiplostim. The efficacy of romiplostim in such disorders is currently under investigation. Here, we review the structure, mechanism, pharmacokinetics, and pharmacodynamics of romiplostim. We also summarize the clinical evidence supporting its use in ITP and other disorders that involve thrombocytopenia, including chemotherapy-induced thrombocytopenia, aplastic anemia, acute radiation syndrome, perisurgical thrombocytopenia, post-HSCT thrombocytopenia, and liver disease.

Keywords:

• immune thrombocytopenia
• pharmacokinetics
• pharmacodynamics
• structure
• thrombopoietin receptor agonist

Acknowledgments

This work was supported by Amgen Inc., Thousand Oaks, CA, USA. Miranda Tradewell, PhD, and Maryann Travaglini, PharmD, ICON (North Wales, PA, USA), provided medical writing support with funding from Amgen Inc.

Abbreviations

ANKRD26, ankyrin repeat domain-containing protein 26; CIT, chemotherapy-induced thrombocytopenia; Fc, fragment crystallizable; HSCT, hematopoietic stem cell transplant; IFN-γ, interferon-γ; IL, interleukin; IQR, interquartile range; ITGB3, integrin beta-3; ITP, immune thrombocytopenia; MDS, myelodysplastic syndrome; MHCII, major histocompatibility complex class II; MPL, myeloproliferative leukemia virus; MYH9-RD, myosin heavy chain 9-related disease; Th1, type 1 T-helper; Th17, type 17 T-helper; TPO, thrombopoietin; TPO-R, thrombopoietin receptor; TPO-RA, thrombopoietin receptor agonist; Treg, regulatory T-cell.

Disclosure

James B Bussel has participated in advisory boards and received consultancy fees from Amgen Inc., Argenx, CSL-Behring, Dova Pharmaceuticals, Kezar, Momenta-J & J, Novartis, Principia, Regeneron, Rigel, and UCB; has participated in speakers bureaus with Novartis and 3S Bio; and has received honoraria from Up to Date. Gerald Soff has received research support from Amgen, Dova Pharmaceuticals, and Janssen Scientific Affairs; has participated in advisory boards and received consultancy fees from Amgen, Anthos Therapeutics, Bayer Pharmaceuticals, Bristol Myers Squibb, Dova Pharmaceuticals, Hengrui (USA) Ltd, Janssen Scientific Affairs, Novartis, and Pfizer; and has received honoraria from Amgen and Bayer Pharmaceuticals. Nichola Cooper has received honoraria for speaking engagements and participated in advisory boards with Amgen, Novartis, Principia, and Rigel; and has received support for clinical trials from Amgen, Novartis, Rigel, Principia, and UCB. Tatiana Lawrence is an employee and stockholder of Amgen. Adriana Balduzzi has received honoraria, advisory board, lectures, speakers bureaus, and/or meeting/travel assistance from Amgen, Novartis, Medac, and Neovii, outside the submitted work. The authors report no other conflicts of interest in this work.