Benralizumab for patients with mild to moderate, persistent asthma (BISE): a randomised, double-blind, placebo-controlled, phase 3 trial

DP1 receptor signaling prevents the onset of intrinsic apoptosis in eosinophils and functions as a transcriptional modulator

“…Moreover, there is substantial literature on the beneficial effects of the reduction of circulating eosinophils in eosinophilic asthma . In fact, depletion of eosinophils by antibody‐dependent cell‐mediated cytotoxicity (ADCC) has been recently shown to effectively improve airway resistance and disease scores in asthma patients with ≥300 eosinophils/μl blood . The anti‐IL‐5Rα antibody benralizumab (MEDI‐563) binds to circulating eosinophils and induces apoptosis and ADCC of eosinophils and basophils in vitro.…”

“…7 In fact, depletion of eosinophils by antibody-dependent cellmediated cytotoxicity (ADCC) has been recently shown to effectively improve airway resistance and disease scores in asthma patients with ≥300 eosinophils/ l blood. 72,73 The anti-IL-5R antibody benralizumab (MEDI-563) binds to circulating eosinophils and induces apop-tosis and ADCC of eosinophils and basophils in vitro. The compound depletes human bone marrow derived mononuclear cells of eosinophil precursors and eosinophils of peripheral blood of nonhuman primates and binds to eosinophils in nonhuman primate lung tissue (bronchi, small airways, bronchial parenchyma).…”

Human eosinophils and mast cells: Birds of a feather flock together

“…The receptor for IL‐5 is a heterodimer complex which consists in a unique α subunit, required for signaling, and a common β subunit shared with IL‐3 and GM‐CSF receptors, that regulates binding affinity . Human eosinophils express IL‐5R throughout development and maturation and both IL‐5 and its receptor have been successfully targeted in several clinical trials utilizing anti‐IL‐5 antibodies, ie, reslizumab, mepolizumab and benralizumab, the latter specifically targeting the IL‐5 receptor α subunit with an antibody engineered to have enhanced antibody‐dependent cellular cytotoxicity (ADCC) activity . There have been reports that human MCs also express IL‐5R; however, its functional role is not yet understood .…”

“…85 Human eosinophils express IL-5R throughout development and maturation 86 and both IL-5 and its receptor have been successfully targeted in several clinical trials utilizing anti-IL-5 antibodies, ie, reslizumab, 87 mepolizumab 88 and benralizumab, the latter specifically targeting the IL-5 receptor α subunit with an antibody engineered to have enhanced antibodydependent cellular cytotoxicity (ADCC) activity. 89 There have been reports that human MCs also express IL-5R; however, its functional role is not yet understood. 90 Of note, Otani et al 91 demonstrated…”

Targeting cytokines in asthma therapy: could IL-37 be a solution?

“…Also antibodies neutralizing IL-9 (MEDI-528 [9]) or IL-13 (lebrikizumab [10], GSK679586 [11], IMA-026 [12]) were discontinued due to lack of efficacy in clinical asthma trials. While another IL-13 neutralizing antibody (tralokinumab [13]) is now tested phase III clinical trial, to date only anti-IL-5 antibodies (benralizumab [14], mepolizumab [15], reslizumab [16]) have been approved for treatment of severe persistent, allergic asthma with high eosinophil counts. The relatively modest effects of these candidates for asthma therapy emphasized that asthma is a complex disease syndrome with many phenotypes/endotypes, which require tailored therapy, and that targeting TH2-cytokines could be a treatment option in a special population of asthma patients displaying hypereosinophilia.…”