A Review of Romiplostim Mechanism of Action and Clinical Applicability

James B Bussel,1 Gerald Soff,2 Adriana Balduzzi,3 Nichola Cooper,4 Tatiana Lawrence,5 John W Semple6,7 1Department of Pediatrics, Division of Hematology, Weill Cornell Medicine, New York, NY, USA; 2Department of Medicine, Hematology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; 3Clinica Pediatrica Università degli Studi di Milano Bicocca, Ospedale San Gerardo, Monza, Italy; 4Hammersmith Hospital, Imperial College, London, UK; 5Amgen Inc., Thousand Oaks, CA, USA; 6Division of Hematology and Transfusion Medicine, Lund University, Lund, Sweden; 7Department of Pharmacology, University of Toronto, Toronto, ON, CanadaCorrespondence: James B BusselDepartment of Pediatrics, Division of Hematology, Weill Cornell Medicine, 525 East 68th St, P695, New York, NY, 10065, USATel +1 917 291 5091Fax +1 212 746 8609Email jbussel@med.cornell.eduAbstract: 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