Drugs
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Four medicinal cancer biological blockbusters will end their patent lifespan by 2020. It is estimated that the total market for cancer biologicals will reach approximately US$68 billion at that time. Approximately 20 biosimilars have entered the European market since the launch of the original approval guidelines in 2005, and four biosimilars have been approved in the USA since 2015. ⋯ High expectations are being placed on the cost savings, safety, and efficacy of these products. The entry costs for biosimilars and the pricing reaction of their originator products will determine the true savings by troubled health systems in dire need of cost cuts. This article discusses basic principles of biosimilars in hematology and oncology, the current status of their clinical development, and trends of acceptance by healthcare providers, and provides insight into potential future challenges.
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Avelumab (Bavencio®) is an intravenously administered programmed cell death ligand-1-blocking human antibody initially developed by EMD Serono Inc. (the biopharmaceutical division of Merck KGaA, Darmstadt, Germany) [now jointly developed and commercialized by EMD Serono Inc. and Pfizer] for the treatment of various tumours. It has received accelerated approval in the USA for the treatment of metastatic Merkel cell carcinoma (mMCC) in adults and paediatric patients aged ≥12 years. The marketing authorization application for avelumab in the treatment of mMCC is undergoing regulatory review in the EU, the biologics license application for avelumab in the treatment of urothelial carcinoma is undergoing priority review by the FDA, and avelumab is in various stages of development internationally for a variety of cancers. This article summarizes the milestones in the development of avelumab leading to this first approval for mMCC.
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Naldemedine (Symproic®) is an orally active µ-opioid receptor antagonist being developed by Shionogi & Co., Ltd. that has been approved in the USA and Japan for the treatment of opioid-induced constipation. The drug inhibits peripheral µ-opioid receptors such as those present in the gastrointestinal tract and has minimal or no effect on central opioid activity. This article summarizes the milestones in the development of naldemedine leading to its first global approval in the USA for the treatment of opioid-induced constipation in patients with chronic non-cancer pain.
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The Janus kinase/signal transduction and activator of transcription (JAK-STAT) signaling pathway is implicated in the pathogenesis of inflammatory and autoimmune diseases including rheumatoid arthritis, psoriasis, and inflammatory bowel disease. Many cytokines involved in the pathogenesis of autoimmune and inflammatory diseases use JAKs and STATs to transduce intracellular signals. Mutations in JAK and STAT genes cause a number of immunodeficiency syndromes, and polymorphisms in these genes are associated with autoimmune diseases. ⋯ This review describes the JAK-STAT pathway, outlines its role in autoimmunity, and explains the rationale/pre-clinical evidence for targeting JAK-STAT signaling. The safety and clinical efficacy of the Jakinibs are reviewed, starting with the FDA-approved Jakinib tofacitinib, and continuing on to next-generation Jakinibs. Recent and ongoing studies are emphasized, with a focus on emerging indications for JAK inhibition and novel mechanisms of JAK-STAT signaling blockade.
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Plecanatide (Trulance(TM)) is an oral guanylate cyclase-C agonist that is being developed by Synergy Pharmaceuticals for the treatment of gastrointestinal disorders, such as chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). It is a synthetic analogue of human uroguanylin, a 16 amino acid peptide that regulates ion and fluid transport in the gastrointestinal tract. ⋯ Plecanatide is undergoing phase III investigation in IBS-C. This article summarizes the milestones in the development of plecanatide leading to this first approval in CIC.