Drugs
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Lenvatinib (Lenvima™) is a multitargeted receptor kinase inhibitor that inhibits the kinase activities of vascular endothelial-derived growth factor receptors 1, 2 and 3, fibroblast growth factor receptors 1, 2, 3 and 4, platelet-derived growth factor receptor α, RET and KIT. In addition to their role in normal cellular function, these kinases have been implicated in pathogenic angiogenesis, tumour growth and cancer progression. Lenvatinib is being developed by Eisai Co. ⋯ Lenvatinib has orphan designation in the EU and Japan for use in differentiated thyroid cancer. In addition, an ongoing global, phase 3 trial is evaluating the use of lenvatinib as first-line treatment in unresectable hepatocellular carcinoma. This article summarizes the milestones in the development of lenvatinib leading to this first approval in locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer.
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The single-tablet regimen of the hepatitis C virus (HCV) NS5A inhibitor ledipasvir and the HCV NS5B polymerase inhibitor sofosbuvir (ledipasvir/sofosbuvir; Harvoni(®)) was recently approved in the US and the EU. The phase III ION trials included treatment-naive (ION-1 and -3) or treatment-experienced (ION-2) patients with chronic HCV genotype 1 infection (≈20 % of patients in ION-1 and -2 had cirrhosis, whereas no patient in ION-3 had cirrhosis). A sustained virological response 12 weeks' post-treatment (SVR12) was seen in 99 % of treatment-naive patients receiving ledipasvir/sofosbuvir for 12 weeks in ION-1, with no additional benefit conferred by the addition of ribavirin or extending the treatment duration to 24 weeks. ⋯ Data also support the use of ledipasvir/sofosbuvir in chronic HCV genotype 4 infection, in HCV and HIV co-infection and, in combination with ribavirin, in patients with chronic HCV genotype 1 or 4 infection who have decompensated cirrhosis or are liver transplant recipients and in chronic HCV genotype 3 infection. Oral ledipasvir/sofosbuvir was generally well tolerated. In conclusion, ledipasvir/sofosbuvir is an important new single-tablet regimen that represents a significant advance in the treatment of chronic hepatitis C.
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Novartis has developed oral and intravenous formulations of panobinostat (Farydak(®)), a histone deacetylase (HDAC) inhibitor, for the treatment of cancer. HDACs have important roles in maintaining chromatin structure and in regulating gene expression, including that of tumour suppressor genes, and thus represent valid targets in the search for cancer therapeutics. ⋯ Panobinostat is in various stages of clinical development worldwide for a range of haematological and solid tumours. This article summarizes the milestones in the development of panobinostat leading to this first approval for multiple myeloma.
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The discovery of immune inhibitory checkpoints has revolutionized the approach to the systemic treatment of cancer. The programmed death 1 (PD-1) inhibitory checkpoint, in particular, has played a key role in understanding how certain cancers can evade immune surveillance. ⋯ In this review, we discuss the role of the PD-1 pathway in the immune system and the anti-cancer mechanism of action of inhibiting the PD-1/PD-L1 interaction. We also review the efficacy and safety data of currently approved and in-development anti-PD-1 agents, and explore the next steps to further improve patient outcomes.
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Oral naloxegol (Movantik™, Moventig(®)), a peripherally acting μ-opioid receptor antagonist, inhibits opioid binding in μ-opioid receptors in the gastrointestinal tract. This article reviews the pharmacological properties of naloxegol and its clinical efficacy and tolerability in patients with opioid-induced constipation. ⋯ As a PEGylated naloxone derivative, naloxegol is associated with significant improvements in spontaneous bowel movements, while maintaining levels of opioid-related analgesia (a result of its reduced ability to cross the blood-brain barrier). Naloxegol is a useful option in the treatment of opioid-induced constipation.