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Yanfeng Liu, Ying Wang, Yongxing Gao, Jessica A Forbes, Rehan Qayyum, Lewis Becker, Linzhao Cheng, Zack Z Wang
Megakaryocytes (MKs) are rare hematopoietic cells in the adult bone marrow and produce platelets that are critical to vascular hemostasis and wound healing. Ex vivo generation of MKs from human induced pluripotent stem cells (hiPSCs) provides a renewable cell source of platelets for treating thrombocytopenic patients and allows a better understanding of MK/platelet biology. The key requirements in this approach include developing a robust and consistent method to produce functional progeny cells, such as MKs from hiPSCs, and minimizing the risk and variation from the animal-derived products in cell cultures...
April 2015: Stem Cells Translational Medicine
A Sarpatwari, J M Franklin, J Avorn, J D Seeger, J E Landon, A S Kesselheim
Using data from a large commercial health insurer, we studied prescribing of romiplostim (Nplate) and eltrombopag (Promacta), two drugs for primary immune thrombocytopenia (ITP) for which risk evaluation and mitigation strategies (REMS) with elements to assure safe use were initially imposed and then removed. We identified 103 and 117 new users of romiplostim and eltrombopag, respectively. Use was almost exclusively for FDA-approved indications ("on-label") while the REMS with elements to assure safe use were in place...
February 2015: Clinical Pharmacology and Therapeutics
Allen S Yang
Thrombopoietin (TPO) is a growth factor that stimulates megakaryocytes to increases platelet counts. Due to concerns around the development of autoantibodies in clinical studies of TPO, a novel peptide that bound the TPO receptor was used to develop a TPO mimetic. This peptide has no shared homology with TPO, and therefore avoids the risk of development of antibodies that cross-react with endogenous TPO. The ability of the artificial peptide to bind and stimulate the TPO receptor was improved by dimerization of the peptide, and the stability of the peptide was improved by linking the peptides to the Fc portion of an antibody...
January 2015: Seminars in Hematology
M Imran Aslam, Anthony P Cardile, George E Crawford
Thrombocytopenia is frequently encountered in HIV-infected patients, and the predominant cause is primary HIV-associated thrombocytopenia (PHAT). Standard treatment regimens include optimization of antiretroviral therapy, intravenous immunoglobulin, anti-D, and corticosteroids. Retreatment due to the inability to sustain remission or inferior responses is common, and investigation into the safety and efficacy of alternative therapies is warranted. We describe novel and effective treatment of PHAT with the peptide thrombopoietin receptor agonist romiplostim in a patient with a minimal response to conventional therapy...
January 2014: Journal of the International Association of Providers of AIDS Care
Martine Pettigrew, Kirsten Garces, Robert Deuson, Jeannine Kassis, Vincent Laroche
OBJECTIVES: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by platelet destruction, sub-optimal platelet production, and mild-to-severe bleeding. Nplate® (romiplostim), a thrombopoietin receptor agonist, and intravenous immunoglobulin (IVIg), an expensive and occasionally scarce blood product, are used in the treatment of ITP. The objective of this study was to compare the total cost of treating patients with romiplostim vs IVIg in Québec, Canada. METHODS: A net cost impact model was developed to calculate the annual cost of romiplostim compared with IVIg based on actual practice observations in all patients (n = 95) treated for chronic ITP with IVIg from April 2010 to March 2011 in two participating hospitals...
2013: Journal of Medical Economics
Grant Shimamoto, Colin Gegg, Tom Boone, Christophe Quéva
Peptibodies or peptide-Fc fusions are an attractive alternative therapeutic format to monoclonal antibodies. They consist of biologically active peptides grafted onto an Fc domain. This approach retains certain desirable features of antibodies, notably an increased apparent affinity through the avidity conferred by the dimerization of two Fcs and a long plasma residency time. Peptibodies can be made in E. coli using recombinant technology. The manufacturing process involves fermentation and downstream processing, including refolding and multiple column chromatographic steps, that result in overall yields and quality suitable for commercial development...
September 2012: MAbs
Amit Agarwal
Drug developers are grappling with the impact of personalized medicine on their portfolios. The combination of molecular diagnostics with targeted biologic therapies has been hailed as a recent innovation with few historical analogs to guide behavior. However, if the definition of companion diagnostics is broadened to include any drug whose FDA approved label requires diagnostic testing before prescription then over 50 drugs across multiple therapeutic areas arise. Most importantly for current drug developers, these drugs represent a wide variety of market situations and with sufficient historical data to evaluate different commercialization strategies for the combination...
September 15, 2012: New Biotechnology
Gillian M Keating
Romiplostim (Nplate®) is an Fc-peptide fusion protein (peptibody) that acts as a thrombopoietin receptor agonist; it has no amino acid sequence homology with endogenous thrombopoietin. This article reviews the clinical efficacy and tolerability of subcutaneous romiplostim in adults with immune thrombocytopenia (ITP), as well as summarizing its pharmacological properties. The efficacy of 12 or 24 weeks' therapy with subcutaneous romiplostim was compared with that of placebo in patients with ITP in three randomized, double-blind, multicentre, phase III trials...
February 12, 2012: Drugs
Susan C Nicholson, Janet Peterson, Behin Yektashenas
The US FDA Amendments Act of 2007 was signed into law on 27 September 2007. A provision of this law granted the FDA new powers to enhance drug safety by requiring the pharmaceutical industry to develop Risk Evaluation and Mitigation Strategies (REMS). REMS are deemed necessary when a question exists as to whether the benefits of a drug outweigh its risks. REMS constitute a safety plan with several potential components, including a medication guide, a communication plan, elements to ensure safe use and an implementation system to help guide the prescribers, pharmacists and patients...
February 1, 2012: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
Graham Molineux
Comprised of peptide and carrier components in an overall structure superficially resembling an antibody, romiplostim is the prototype of a new class of protein therapeutics called peptibodies. Romiplostim (AMG 531, Nplate) was designed to evade the immune response to recombinant thrombopoietin and offer a new method of treatment for patients with immune thrombocytopenia (ITP), an "orphan" disease. In contrast with agents designed to suppress immune function or hinder the processes of platelet destruction, romiplostim works by stimulating the production of new platelets...
March 2011: Annals of the New York Academy of Sciences
M E Mingot Castellano
Primary Immune thrombocytopenia or idiopathic thrombocytopenic purpura (ITP) is an acquired immune disorder presenting with abnormal hemorrhagic symptoms resulting from a decrease in the number of platelets. The disorder used to be attributed to increased destruction of platelets mediated by antibodies. In the past few years, the description of its etiopathology has changed. A deficiency in the marrow production of thrombocytes has been demonstrated; because it is associated with increased peripheral platelet destruction, the deficiency cannot be compensated...
December 2010: Methods and Findings in Experimental and Clinical Pharmacology
Oliver Meyer, Abdulgabar Salama
BACKGROUND: The new thrombopoietin mimetics (TM) romiplostim (Nplate®) and eltrombopag (Revolade®) have been demonstrated to increase platelet counts in the majority of patients with chronic autoimmune thrombocytopenia (ITP). Platelet counts in chronic ITP may fluctuate significantly due to infections, but it is unknown if this holds true in patients being treated with TM. PATIENTS AND METHODS: 13 adult patients with refractory chronic ITP were treated with the new TM...
2011: Onkologie
Ping Wei
Megakaryopoiesis and thrombopoiesis are the central biological processes of platelet generation. Severe thrombocytopenia is a major morbidity and mortality factor in several diseases and represents a significant unmet medical need. Since the discovery of thrombopoietin (TPO) as the primary physiological regulator of megakaryopoiesis, a number of therapeutics have been developed for thrombocytopenia and been tested in preclinical models and human clinical trials. The TPO mimetics romiplostim (Nplate(®) or AMG531) and eltrombopag (Promacta(®)) have recently been approved for the treatment of adult chronic idiopathic (immune) thrombocytopenic purpura (ITP) and are successful examples of these endeavors...
2011: Cancer Treatment and Research
H Sallmon, R K Gutti, F Ferrer-Marin, Z-J Liu, M C Sola-Visner
The Food and Drug Administration recently approved two novel thrombopoiesis-stimulating agents, Romiplostim (AMG-531, Nplate) and Eltrombopag (Promacta), for the treatment of adults with immune thrombocytopenic purpura. For physicians taking care of critically ill neonates, this offers the opportunity of decreasing platelet transfusions and potentially improving the outcomes of neonates with severe and prolonged thrombocytopenia. However, several developmental factors need to be taken into consideration. First, the population of thrombocytopenic neonates likely to benefit from these agents needs to be carefully selected...
December 2010: Journal of Perinatology: Official Journal of the California Perinatal Association
Robert J Cersosimo
BACKGROUND: Immune thrombocytopenic purpura (ITP) is characterized by platelet deficiency due to platelet destruction and/or inadequate production. Initial therapy consists of corticosteroids or intravenous immunoglobulin (IVIg). Patients with chronic refractory disease might undergo splenectomy. Although there is no treatment of choice in those who do not respond to splenectomy, immunosuppressive agents are typically prescribed. Romiplostim is the first available drug in a recently developed class of agents that work through stimulation of the thrombopoietin (TPO) receptor (c-Mpl) to increase platelet production...
September 2009: Clinical Therapeutics
Faranak Jamali, Steven Lemery, Kassa Ayalew, Suzanne Robottom, Kathy Robie-Suh, Dwaine Rieves, Richard Pazdur
PURPOSE: On August 22, 2008, Romiplostim (Nplate for Injection) received approval from the US Food and Drug Administration (FDA) for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. This report summarizes the FDA analyses of the clinical data supporting this approval. EXPERIMENTAL DESIGN: The FDA reviewed data from two double-blind, placebo-controlled clinical studies, an uncontrolled extension study, and supportive studies...
July 2009: Oncology (Williston Park, NY)
Simon Panzer
Platelets play a pivotal role in maintaining hemostatic competence. Thrombocytopenia, irrespective of its etiology, is associated with a risk for bleeding. Treatment modalities for chronic idiopathic thrombocytopenic purpura (ITP) are numerous, but the response is variable, often disappointing and associated with high risks. Better understanding of the pathophysiology of chronic ITP, indicating impaired platelet production rather than simply increased turnover, led to clinical trials aimed at increasing platelet production with thrombopoietin receptor agonists...
February 2009: Drugs of Today
(no author information available yet)
Romiplostim (Nplate - Amgen), a recombinant fusion protein injected subcutaneously, and eltrombopag (Promacta - GlaxoSmithKline), a non-peptide taken orally, have been approved by the FDA for treatment of chronic immune thrombocytopenic purpura (ITP) refractory to corticosteroids, immunoglobulins and/or splenectomy.
February 9, 2009: Medical Letter on Drugs and Therapeutics
Douglas B Cines, Uma Yasothan, Peter Kirkpatrick
In August 2008, romiplostim (Nplate; Amgen), a thrombopoietin receptor agonist, was approved by the US FDA for the treatment of thrombocytopaenia in patients with chronic immune thrombocytopaenic purpura who have had an insufficient response to corticosteroids, immunoglobulins or splenectomy.
November 2008: Nature Reviews. Drug Discovery
David J Kuter
Various agents to treat immune thrombocytopenic purpura (ITP) have been developed on the principle that stimulating the thrombopoietin (TPO) receptor would increase platelet production. First-generation agents--recombinant human thrombopoietin (rHuTPO) and pegylated recombinant human megakaryocyte growth and development factor (PEG rHuMGDF)--showed promise, but observations of antibody formation to PEG rHuMGDF led to the discontinuation of development of both agents. Second-generation agents--the TPO peptide mimetics, TPO non-peptide mimetics, and TPO agonist antibodies--have been developed to reduce or eliminate the problem of antigenicity...
February 2008: European Journal of Haematology. Supplementum
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