Drugs of today
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Idiopathic pulmonary fibrosis (IPF) conveys a median survival of 3 years and until recently has lacked effective therapies. Nintedanib, an orally available, small-molecule tyrosine kinase inhibitor with selectivity for vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) receptors has recently been shown, in two pivotal phase III studies, to effectively slow IPF disease progression. Consequently, nintedanib was given accelerated approval by the FDA in October 2014 for the treatment of IPF. This monograph explores the preclinical rationale for the antifibrotic role of nintedanib and provides an overview of the available data on pharmacokinetics, efficacy and safety.
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An estimated 184 million people worldwide have hepatitis C virus (HCV) infection. Chronic infection can ultimately result in liver cirrhosis and hepatic failure. Eradication of the virus by antiviral treatment can hinder the development of the aforementioned complications. ⋯ One of the newest members of this family is the all-oral regimen (ombitasvir/paritaprevir/ritonavir co-packaged with dasabuvir) that has recently received FDA approval for the treatment of adult patients with genotype 1 HCV infection, including those with compensated cirrhosis. This new combination was found to be safe and well tolerated with high rates of sustained virologic response of up to 100%. An overview of the current knowledge about this regimen is reviewed herein.
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The marker CD19 is frequently expressed on the surface of malignant B cells including non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL), which makes it an attractive target for antineoplastic therapy (1). T cells are part of the immune surveillance system for malignant cells (2). Blinatumomab is a bispecific T cell engager (BiTE(®)) antibody that binds both CD3-positive T cells and CD19-positive B cells via its two variable antigen-binding domains. ⋯ It has shown efficacy in ALL with minimal residual disease, relapsed/refractory ALL, and NHL in phase I and II clinical trials. With a favorable safely profile and promising results, blinatumomab was granted accelerated FDA approval to treat B-cell ALL in December 2014. Herein, we will review the most relevant data related to blinatumomab in ALL.
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When oral hypoglycemic agents do not successfully suppress hyperglycemia, the traditional approach has been to add insulin injections. With the coming of glucagon-like peptide 1 (GLP-1) receptor agonists carrying the benefits of weight loss and reduced risk of hypoglycemia, it has been suggested that GLP-1 agents should be used instead. There is equivalent lowering of HbA1c with either treatment. ⋯ Lower dosage of insulin degludec reduces the risk of hypoglycemia. Liraglutide combats the weight gain that accompanies the introduction of insulin therapy, and a reduced dose of liraglutide induces less GI intolerance. This first combined basal insulin-GLP-1 receptor agonist combination represents a conceptual advance in the treatment of insulin-requiring type 2 diabetes.
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Our increased understanding of the molecular subsets of non-small cell lung cancer (NSCLC) has led to the development of highly effective targeted therapies. In particular, the outcomes of patients with advanced NSCLC driven by the EML4-ALK fusion protein, which comprise 3-5% of cases, have remarkably improved with the use of crizotinib, an oral multi-tyrosine kinase inhibitor that targets ALK. However, patients inevitably develop progression while on crizotinib due to various mechanisms of resistance. ⋯ Due to the impressive results of early phase studies, alectinib was approved for the treatment of advanced ALK-positive NSCLC in Japan, while it has been granted a breakthrough therapy designation by the FDA. A phase III trial is currently ongoing. This review will describe the biology and significance of ALK rearrangements in NSCLC, ALK inhibition by crizotinib and mechanisms of resistance, as well as the preclinical and clinical evidence for the novel ALK inhibitor alectinib.