Drugs
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A gradual rise in drug-resistant trends among Gram-negative organisms, especially carbapenem-resistant (CR) Enterobacteriaceae (CRE), CR-Pseudomonas aeruginosa, and extensively-drug-resistant (XDR) Acinetobacter baumannii, poses an enormous threat to healthcare systems worldwide. In the last decade, many pharmaceutical companies have devoted enormous resources to the development of new potent antibiotics against XDR Gram-negative pathogens, particularly CRE. Some of these novel antibiotics against CRE strains are β-lactam/β-lactamase-inhibitor combination agents, while others belong to the non-β-lactam class. ⋯ Although active against extended-spectrum and AmpC β-lactamase-producing Enterobacteriaceae, delafloxacin does not show in vitro activity against CRE. Murepavadin is shown to be specifically active against CR- and colistin-resistant P. aeruginosa strains. Despite successful development of novel antibiotics, strict implementation of an antibiotic stewardship policy in combination with the use of well-established phenotypic tests and novel multiplex PCR methods for detection of the most commonly encountered β-lactamases/carbapenemases in hospitals is important for prescribing effective antibiotics against CRE and decreasing the resistance burden due to CRE.
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Pegaspargase (Oncaspar®), a pegylated form of native Escherichia coli-derived L-asparaginase (hereafter referred as E. coliL-asparaginase), is indicated in the USA and EU for the treatment of acute lymphoblastic leukaemia (ALL) as a component of multi-agent chemotherapy in paediatric and adult patients. Relative to E. coliL-asparaginase, pegaspargase has a prolonged circulation time, thereby offering less frequent administration. Moreover, pegylation of E. coliL-asparaginase may diminish the immunogenicity of the enzyme. ⋯ Pegaspargase had a manageable tolerability profile in paediatric and adult patients with newly diagnosed ALL, with the most commonly occurring adverse events being generally consistent to that seen with E. coliL-asparaginase. Pegaspargase treatment in patients with relapsed ALL and hypersensitivity to E. coliL-asparaginase had a similar tolerability profile to that observed in patients with newly diagnosed ALL. Given the potentially reduced immunogenicity and more convenient dosage regimen over E. coliL-asparaginase, pegaspargase remains an important and effective treatment option for paediatric and adult patients with ALL, including those with hypersensitivity to E. coliL-asparaginase.
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The article Sarecycline: First Global Approval, written by Emma D. Deeks, was originally published Online First without open access. After publication in volume 79, issue 3, pages 325-329 Almirall, LLC., requested that the article be Open Choice to make the article an open access publication. Post-publication open access was funded by Almirall, LLC.
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Tagraxofusp (tagraxofusp-erzs) [Elzonris™] is an intravenously administered CD123-directed cytotoxin (composed of human interleukin-3 and a truncated diphtheria toxin payload) that was developed by Stemline Therapeutics, Inc. for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN). In December 2018, tagraxofusp received its first global approval in the USA for the treatment of BPDCN in adults and in paediatric patients aged 2 years and older. A centralized registration application for the use of tagraxofusp in patients with BPDCN is under review in the EU. This article summarizes the milestones in the development of tagraxofusp leading to its first global approval for the treatment of BPDCN.
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Roxadustat (Ai Rui Zhuo® in China) is an orally administered, small molecule hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor that is being developed by FibroGen, in collaboration with Astellas and AstraZeneca, for the treatment of anaemia in patients with dialysis-dependent chronic kidney disease (CKD), non-dialysis-dependent CKD and in patients with myelodysplastic syndromes. The drug reversibly binds to and inhibits HIF-prolyl hydroxylase enzymes that are responsible for the degradation of transcription factors in the HIF family under normal oxygen conditions. Inhibition of these enzymes reduces HIF breakdown and promotes HIF activity, leading to an increase in endogenous erythropoietin production, thereby enhancing erythropoiesis. ⋯ Roxadustat is approved in China and is under regulatory review in Japan for the treatment of anaemia in patients with dialysis-dependent CKD. Studies are underway to investigate long-term cardiovascular outcomes with roxadustat versus placebo (for non-dialysis-dependent CKD) or standard of care (for dialysis-dependent CKD). This article summarizes the milestones in the development of roxadustat leading to this first approval.