Romiplostim

Amgen's AMG 531, a thrombopoietin-mimetic peptibody that raises platelet counts by activating the TPO receptor, FDA approved as Nplate since August 22, 2008 for immune thrombocytopenia and since 2021 for the hematopoietic syndrome of acute radiation syndrome.

Also referenced as: AMG 531, AMG-531, Nplate, Romiplate

Also appears in: Immune

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What is Romiplostim?

Romiplostim, developed by Amgen as AMG 531 and marketed as Nplate, is a peptibody rather than a peptide in the ordinary sense. The US label describes it as an Fc-peptide fusion protein made of two identical single-chain subunits, each a human IgG1 Fc domain covalently linked at its C-terminus to a peptide carrying two thrombopoietin (TPO) receptor-binding domains, so one molecule presents four receptor-binding motifs. It is produced by recombinant DNA technology in Escherichia coli and has no amino acid sequence homology to endogenous TPO. The peptide portion descends from a 14-residue sequence, Ile-Glu-Gly-Pro-Thr-Leu-Arg-Gln-Trp-Leu-Ala-Ala-Arg-Ala, selected from recombinant peptide libraries for binding to the human TPO receptor; the monomer bound with a dissociation constant of about 2 nM, and a dimer reached an EC50 of 100 pM, equipotent with the natural cytokine in cell assays (Cwirla et al., Science, 1997;276(5319):1696–1699). The Fc scaffold gave a long half-life and sidestepped the failure of first-generation recombinant TPO, against which some patients raised antibodies that neutralized their own TPO (Mytych et al., British Journal of Haematology, 2020;190(6):923–932).

Romiplostim is a hospital and hematology-clinic biologic approved in the US for immune thrombocytopenia (ITP) and for survival after acute radiation exposure. It has no research-peptide-market footprint.

How it works

• Agonist at the TPO receptor (Mpl). AMG 531 competes with radiolabeled TPO for binding to Mpl on BaF3-Mpl cells and normal platelets, and triggers rapid tyrosine phosphorylation of Mpl, JAK2 and STAT5, the cascade TPO itself uses (Broudy and Lin, Cytokine, 2004;25(2):52–60). The US label describes the mechanism as analogous to endogenous TPO.
• Drives megakaryocyte growth and maturation. In vitro, AMG 531 stimulates colony-forming unit-megakaryocyte growth dose-dependently, acts in concert with erythropoietin, stem cell factor, interleukin-3 and interleukin-6, and supports mature polyploid megakaryocytes identical to those in TPO-stimulated cultures (Broudy and Lin, Cytokine, 2004;25(2):52–60).
• Dose-dependent, delayed platelet rise in humans. In the first-in-human study, 48 healthy adults received single intravenous (0.3 to 10 µg/kg) or subcutaneous (0.1 to 2 µg/kg) injections; platelet counts rose dose-dependently, peaked on days 12 to 16, reached a mean of 1,380 × 10^9/L after the highest intravenous dose, and were near baseline by day 28 (Wang et al., Clinical Pharmacology and Therapeutics, 2004;76(6):628–638). The label reports a median half-life of 3.5 days (range 1 to 34 days) in adults with ITP, with elimination partly dependent on TPO receptors on platelets.
• Designed to limit immunogenicity. Across 13 adult ITP trials, 6.2% of 961 patients developed anti-romiplostim binding antibodies and 0.4% neutralizing antibodies, without effect on platelet counts; none developed TPO-neutralizing antibodies (Mytych et al., British Journal of Haematology, 2020;190(6):923–932).

Research status

Phase 1–2 in chronic ITP (NCT00111475). Twenty-four previously treated adults received two doses of AMG 531 from 0.2 to 10 µg/kg, and 21 were randomized to six weekly injections of 1, 3 or 6 µg/kg or placebo. Platelet counts rose dose-dependently, 10 of 16 patients on 1 or 3 µg/kg reached the target range, no major adverse events were attributed to the drug, and 4 of 41 patients had transient post-treatment worsening of thrombocytopenia (Bussel et al., New England Journal of Medicine, 2006;355(16):1672–1681).

Pivotal phase 3 trials (NCT00102323, NCT00102336). Two parallel 24-week, double-blind trials randomized 63 splenectomized and 62 non-splenectomized adults with chronic ITP 2:1 to weekly romiplostim or placebo. A durable platelet response (at least 50 × 10^9/L in 6 or more of the last 8 weeks) was achieved by 16 of 42 splenectomized patients versus 0 of 21 on placebo (p=0.0013) and by 25 of 41 non-splenectomized patients versus 1 of 21 (p<0.0001); overall response rates were 79% and 88% against 0% and 14%, and 87% of romiplostim patients reduced or stopped concurrent ITP therapy versus 38% on placebo (Kuter et al., Lancet, 2008;371(9610):395–403). These trials supported the approval of BLA 125268 on August 22, 2008.

Romiplostim versus standard of care (NCT00415532). An open-label 52-week trial randomized 234 non-splenectomized adults 2:1 to weekly romiplostim or standard care. Treatment failure occurred in 11% versus 30% (odds ratio 0.31), splenectomy in 9% versus 36% (odds ratio 0.17), and the platelet response rate was 2.3 times higher, with less bleeding and fewer transfusions (Kuter et al., New England Journal of Medicine, 2010;363(20):1889–1899). In a single-arm extension of 292 adults with 614 patient-years of exposure, 95% responded at least once and thrombotic events occurred in 6.5% without relation to platelet count (Kuter et al., British Journal of Haematology, 2013;161(3):411–423). In a phase 2 study of adults with ITP of 6 months or less (NCT01143038), more than 90% responded over 12 months and 24 patients (32%) reached treatment-free remission of at least 24 weeks after romiplostim was stopped (Newland et al., British Journal of Haematology, 2016;172(2):262–273).

Pediatric ITP. The first randomized pediatric trial (NCT00515203) treated 22 children for 12 weeks; 15 of 17 (88%) on romiplostim versus 0 of 5 on placebo held a count of at least 50 × 10^9/L for 2 consecutive weeks (p=0.0008) (Bussel et al., Blood, 2011;118(1):28–36). The phase 3 trial (NCT01444417) randomized 62 children in the US, Canada and Australia to 24 weeks of romiplostim or placebo; durable platelet response occurred in 22 of 42 (52%) versus 2 of 20 (10%) (odds ratio 9.1; p=0.002), serious adverse events in 24% versus 5%, and no patient withdrew for adverse events (Tarantino et al., Lancet, 2016;388(10039):45–54). A single-arm phase 3b study (NCT02279173) followed 203 children for a median of about 3 years: 11 patients (5.4%) achieved sustained treatment-free responses and 8 of 63 evaluable patients (12.7%) had grade 2 reticulin at year 2 (Grainger et al., Blood Advances, 2023;7(3):396–405). Drugs@FDA records the pediatric efficacy supplement as approved on December 14, 2018.

Hematopoietic syndrome of acute radiation syndrome. A single dose of romiplostim produced 100% 30-day survival in mice exposed to a lethal 7 Gy dose of gamma rays, with near-normal recovery of blood, marrow and progenitor cells (Yamaguchi et al., Scientific Reports, 2018;8(1):10659). The approval rests on a blinded study described in the label: 80 rhesus monkeys received 6.8 Gy total-body irradiation and a single subcutaneous dose of saline or romiplostim 5 mg/kg 24 hours later, and 60-day survival was 72.5% (29 of 40) with romiplostim versus 32.5% (13 of 40) with control. The efficacy supplement was approved on January 28, 2021 under the animal rule, and the indication covers adults and children, including term neonates.

Myelodysplastic syndromes: a halted trial. A randomized phase 2 trial (NCT00614523) assigned 250 patients with lower-risk MDS 2:1 to 58 weeks of romiplostim or placebo. The primary endpoint, clinically significant bleeding events, missed significance (hazard ratio 0.83; p=0.13), and a data monitoring committee halted study drug over an interim acute myeloid leukemia hazard ratio of 2.51 (Giagounidis et al., Cancer, 2014;120(12):1838–1846). Five-year follow-up found AML in 12% versus 11% and death in 56% versus 54% (Kantarjian et al., Lancet Haematology, 2018;5(3):e117–e126). Romiplostim is not approved for MDS, and the US label carries a warning on progression to acute myeloid leukemia.

Chemotherapy-induced thrombocytopenia (CIT). RECITE (NCT03362177) randomized 165 patients with persistent CIT on oxaliplatin-based chemotherapy for gastrointestinal cancers 2:1 to romiplostim or placebo for three cycles. The proportion with no CIT-induced chemotherapy modifications in cycles 2 and 3 was 84% versus 36% (odds ratio 10.16; p<0.001); grade 3 or higher adverse events occurred in 37% versus 22%, mainly chemotherapy effects, and thromboembolic events in 2% versus none (Al-Samkari et al., New England Journal of Medicine, 2026;394(11):1061–1073). PROCLAIM (NCT03937154), in 145 patients with lung, ovarian or breast cancer, reached primary completion on March 10, 2026, with study completion estimated for February 23, 2027. As of November 2026, no CIT indication appears in the US label.

Aplastic anemia and other regions. A Korean phase 2 study (NCT02094417) in 35 adults with aplastic anemia refractory to immunosuppression found platelet responses at week 9 in 30% of evaluable patients overall and 70% of the 10 µg/kg cohort (Lee et al., Lancet Haematology, 2019;6(11):e562–e572). In Japan, where Kyowa Kirin markets the molecule as Romiplate for chronic ITP, an additional aplastic anemia indication was approved on June 18, 2019. The European Commission granted Nplate a marketing authorization on February 4, 2009 for chronic ITP in adults, and the EU indication now extends to patients from 1 year of age with chronic ITP.

Safety themes. Romiplostim produced dose-dependent, reversible marrow fibrosis in rats, 10 of 271 ITP trial patients were reported with reticulin deposition, and grades often fell after discontinuation (Kuter et al., Blood, 2009;114(18):3748–3756). The US label reports deep vein thrombosis (1.4%), pulmonary embolism (1.2%) and myocardial infarction (0.8%) in the ITP population, occurring regardless of platelet count. In children, 8 of 280 trial patients (2.9%) developed neutralizing antibodies, most while still responding (Bowers et al., Blood Advances, 2021;5(23):4969–4979).

Common dosage forms

• Nplate for injection, single-dose vials. A sterile, preservative-free white lyophilized powder for subcutaneous injection, supplied in single-dose vials of 125 mcg, 250 mcg and 500 mcg of romiplostim, given in a clinical setting.
• Romiplate (Japan). The Kyowa Kirin presentation is a 250 mcg vial for subcutaneous injection.
• No other presentation. No oral, pen or compounded romiplostim product exists.

Key considerations

• Regulatory status. The FDA Approved status reflects the August 22, 2008 approval of Nplate (romiplostim) under BLA 125268 for thrombocytopenia in patients with chronic immune thrombocytopenic purpura who have had an insufficient response to corticosteroids, immunoglobulins or splenectomy. Later supplements added children aged 1 year and older with ITP for at least 6 months (December 14, 2018), a broader adult ITP population (October 17, 2019) and survival after acute myelosuppressive radiation exposure (January 28, 2021), the latter approved on animal data alone.
• A peptibody, not a peptide. Each molecule is two IgG1 Fc chains carrying four TPO receptor-binding peptide motifs, expressed in Escherichia coli and given by subcutaneous injection; the Fc scaffold gives it a multi-day half-life, and the peptide shares no sequence with TPO.
• Benefit is on-treatment, with remission the exception. Platelet counts depend on continued weekly dosing, treatment-free remission is uncommon outside early-stage adult disease, and counts can transiently fall below baseline after withdrawal.
• Thrombosis and marrow reticulin are the labeled trade-offs. Thromboembolic events occur regardless of platelet count, so a normal count is not protective, and reticulin deposition is usually modest and reversible on stopping but argues for marrow surveillance in long-term users.
• Naming. AMG 531, romiplostim, Nplate and Romiplate denote the same peptibody; eltrombopag and avatrombopag are oral small-molecule TPO receptor agonists, not aliases.