Drugs of today
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Cystic fibrosis (CF) is a life-shortening disorder that affects over 30,000 people in the U. S. and 70,000 worldwide. CF is caused by mutations in the CFTR gene, which codes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. ⋯ In the current review, we summarize the development and clinical experience with VX-770 (ivacaftor), a small molecule that increases CFTR chloride conductance in vitro and in vivo, including wild-type and G551D CFTR. The G551D CFTR mutation is the third most common CF disease-causing mutation, in which the CFTR protein localizes to the epithelial cell membrane but has defective gating. With restoration of adequate CFTR function through pharmacotherapy, it is possible that the clinical course of patients with CF could be markedly improved, including longevity, quality of life and treatment burden.
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Carfilzomib is a second-generation selective proteasome inhibitor that has been recently approved in the use for refractory multiple myeloma. It has been shown to be beneficial in both bortezomib-resistant and bortezomib-naive patients, with a tolerable side effect profile. Peripheral neuropathy is less common in patients receiving carfilzomib compared to bortezomib. Recent and ongoing clinical trials are establishing the role of carfilzomib in the treatment of refractory multiple myeloma.
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Invasive pulmonary aspergillosis is a major cause of morbidity and mortality in immunocompromised patients, particularly those with hematological malignancies in the setting of profound neutropenia and/or hematopoietic stem cell transplant recipients. The optimal therapy for invasive aspergillosis relies on the restoration of leukocyte counts and effective antifungal treatment initiated at the earliest stage of infection. Several alternative antifungal compounds are currently available. A rational approach should take into account not only the degree of certainty of infection (as codified by the EORTC/MSG classification), but also previous exposure to other antifungals, the pharmacokinetic and pharmacodynamic characteristics of the antifungals employed and the clinical characteristics of the patient.
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Imatinib mesylate, a receptor tyrosine kinase inhibitor that has been approved for several oncology conditions, is currently under investigation for pulmonary arterial hypertension. The therapeutic rationale is that its targets, platelet-derived growth factor receptor beta (PDGFR-β) and proto-oncogene c-Kit, are pivotal for the proliferation, migration and apoptosis resistance of peripheral artery smooth muscle cells which reduces the lumen of the pulmonary artery, leading to diminished blood oxygenation and pressure overload in the right heart ventricle. ⋯ Results from two efficacy studies have been reported; while the first missed its primary endpoint (but provided valuable insights on efficacy in subgroups), the phase III IMPRES study and its ongoing extension revealed an impressive degree of added benefit for imatinib against a background of conventional combination therapy. The side effect profile of imatinib in this condition requires more investigation.
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Thirty-seven new launches are considered in the first part of this annual review article, including 36 drugs and biologics that reached their first markets worldwide in 2012 and one additional drug that was launched at the end of December 2011. In addition, 26 significant new line extensions (new indications, new formulations and new combinations of existing drugs) that were launched for the first time in 2012 are discussed in this review. Also included are new drugs and biologics and new line extensions that were approved for the first time between January and December 2012, although they were not launched before the end of the year.