Novel thrombopoietic agents: a new era for management of patients with thrombocytopenia.

fter many decades of an orphan existence, immune thrombocytopenic purpura (ITP) is a central focus for the clinical development of multiple , novel thrombopoietic agents. These agents have the potential to transform the management of ITP and possibly other thrombocytopenic disorders. Now, with the approval of the first agents for clinical use, their role in patient care will become established and their potential risks may be more clearly revealed. The availability of novel thrombopoietic agents for the treatment of patients with thrombocytopenia is remarkable both as a scientific achievement and also as an immediate benefit for patient care. The history of the isolation and characterization of thrombopoietin (TPO) in 1994 and the development of therapeutic throm-bopoietic agents have been recently reviewed. 1 This year the first two agents, romiplostim (previously known as AMG 531) and eltrombopag, will be approved by the US Food and Drug Administration (FDA) for treatment of patients with ITP. The success of these thrombopoietic agents in clinical trials for treatment of ITP 2-4 has stimulated the development of multiple other compounds to enhance platelet production, including the novel small non-peptidyl molecule described in this issue of the journal by Nogami et al. 5 The molecular diversity of these agents, their therapeutic effectiveness, and their potential risks are an important story for hematologists. In this Perspective, we will describe [1] the evolution of understanding of the pathogenesis of ITP, that provided the insight for treatment with thrombopoietic agents; [2] the experience of individual patients with ITP who have received thrombopoietic agents; [3] the molecular spectrum of thrombopoietic agents that are currently in development; [4] the clinical spectrum of targeted thrombocytopenic disorders; and [5] the potential harm from these agents. The clinical development of thrombopoietic agents has been intimately associated with ITP. The low prevalence of ITP, estimated at 9 patients per 10 5 population, 6 is a challenge for clinical trial accrual but also an opportunity for accelerated regulatory approval. ITP is classified by the US FDA as an orphan disease, defined as a condition that affects fewer than 200,000 persons in the United States. An advantage of ITP as a target for clinical trials is that patients are typically healthy, other than for thrombocytopenia, and platelet counts provide objective , accessible outcome measures. An important consideration for development of thrombopoietic agents was the unmet medical need for effective treatment for patients with chronic refractory ITP. To …