Romiplostim (Nplate): Thrombopoietin mimetic peptibody approved for the treatment of chronic ITP

Romiplostim is a thrombopoietin (TPO) mimetic peptibody that increases platelet production by binding and activating the TPO receptor. This agent was approved on August 22, 2008, for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who have experienced an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

Efficacy. The efficacy of romiplostim was assessed in 2 double-blind, placebo-controlled clinical trials (Studies 1 and 2) and in an open-label extension trial. In Studies 1 and 2, patients with chronic ITP who had undergone ≥1 prior treatment and who had a platelet count ≤30×10⁹/L were randomized to treatment with subcutaneous (SC) romiplostim 1 mcg/kg per week or placebo for 24 weeks. Individual dose adjustments were allowed to maintain platelet counts between 50×10⁹/L and 200×10⁹/L. Patients in Study 1 had not undergone a splenectomy; patients in Study 2 had undergone a splenectomy. Patients were assessed for durable platelet response, defined as the achievement of a weekly platelet count ≥50×10⁹/L for any 6 of the last 8 weeks of the treatment period in the absence of rescue medications at any time. In Study 1, 61% of romiplostim-treated patients demonstrated a durable platelet response versus 5% of placebo-treated patients; in Study 2, 38% of romiplostim-treated patients demonstrated a durable platelet response versus 0 placebo-treated patients. Patients were then withdrawn from study medications, and if platelet counts decreased to ≤50×10⁹/L, patients were permitted to receive romiplostim in an open-label extension study. In these patients, platelet counts were increased and maintained regardless of whether patients had received romiplostim or placebo in the previous study. The majority of patients achieved a median platelet count of 50×10⁹/L after receiving 1 to 3 doses of romiplostim.

Safety. This agent is available only through a restricted distribution program (Nplate Network of Experts Understanding and Supporting Nplate and Patients [NEXUS] Program). Treatment with romiplostim increases the risk for deposition of reticulin fiber in the bone marrow. Once a stable romiplostim dose has been identified, blood smears and complete blood counts (CBCs) should be examined monthly for new or worsening morphologic abnormalities or cytopenias. Excessive increases in platelet counts during romiplostim treatment can lead to thrombotic/thromboembolic complications. Stimulation of the TPO receptor on hematopoietic cells may increase the risk for hematologic malignancies. The most common adverse events associated with romiplostim treatment include arthralgia, dizziness, insomnia, myalgia, pain in extremity, and abdominal pain.