Drugs in Clinical Development for Asthma: Summary and Table
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ADIS PROFILE SUMMARY
Drugs in Clinical Development for Asthma: Summary and Table
Ó Springer International Publishing Switzerland 2013
Given the very high prevalence of asthma globally— approximately 300 million people according to recent World Health Organization estimates—and the significant levels of asthma-related morbidity and mortality, the drug pipeline for novel agents to improve outcomes for asthma sufferers is active and well-populated with approximately 20 in phase III and over 90 drugs in phase II development (Table 1). Asthma is broadly categorized into either childhoodonset atopic (allergy-driven) disease or an adult-onset nonatopic form. Novel drugs are aimed at the 5–10 % of the asthma population who fail to respond adequately to current conventional treatment comprising inhaled corticosteroids (ICS), bronchodilators (such as b2 agonists and anticholinergics) and, in severe cases, leukotriene modifiers and monoclonal antibodies (mAbs) such as the subcutaneous (SC) anti-IgE mAb omalizumab for severe atopic disease. Much of the ongoing development is focussed on targeting the underlying disease mechanism rather than the symptoms. To date, most research into biological modifiers has been focussed on interfering with T helper 2 cell (TH2)mediated eosinophil and mast cell activation at the heart of asthma pathophysiology. Some recent trials of products targeting cytokines in this pathway have been disappointing; anti-interleukin (IL)-5 monoclonal antibody (mAb) mepolizumab, anti-IL-13 mAb anrukinzumab and dual anti-IL-4/IL-13 agent AIR645, all failed in phase II trials in moderate-to-severe asthma and the latter two (and many others) were discontinued. These findings highlight asthma complexity and speak to the argument that asthma is a collection of varying phenotypes. Mepolizumab (intravenous [IV]/SC) is now in phase III trials in patients with severe exacerbations and
eosinophilic inflammation, and SC anti-IL-13 mAb lebrikizumab and IV anti-IL-5 mAb reslizumab are also in phase III in this patient population. Other mAbs in phase II include anti-IL-5R benralizumab (SC and IV), anti-IL-13 tralokinumab (SC and IV) and IV QAX-576, anti-IL-4R/Il-13 SC dupilumab, and anti-IL-17 SC brodalumab and IV secukinumab. Inhaled pitrakinra, another IL-4/IL-13 antagonist, is a human recombinant protein and inhaled TPI-ASM 8 is an anti-IL5R oligonucleotide. Agents that stimulate the TH1 response include oral antiCCR3 agent GW766944, SC Toll-like receptor (TLR)-9 agonist CYT003 and intranasal TLR7 agonist GSK2245035—all in phase II. The pipeline contains many inhaled products: b2 agonists including phase II arformoterol in children and olodaterol in adults, and phase III indacaterol and vilanterol; several ICS agents, including ciclesonide, fluticasone, and a dry powder formulation of dexamethasone, in phase III; and numerous ICS/b2 agonist combinations, including a new delivery system of beclomethasone/formoterol in phase II, and vilanterol/fluticasone in phase III. Other phase III agents include masitinib, an oral ty
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