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Review
. 2022 Mar;77(3):778-797.
doi: 10.1111/all.15056. Epub 2021 Sep 16.

From DREAM to REALITI-A and beyond: Mepolizumab for the treatment of eosinophil-driven diseases

Ian D Pavord  1 , Elisabeth H Bel  2 , Arnaud Bourdin  3   4 , Robert Chan  5 , Joseph K Han  6 , Oliver N Keene  7 , Mark C Liu  8 , Neil Martin  9   10 , Alberto Papi  11 , Florence Roufosse  12 , Jonathan Steinfeld  13 , Michael E Wechsler  14 , Steven W Yancey  15
Affiliations
Review

From DREAM to REALITI-A and beyond: Mepolizumab for the treatment of eosinophil-driven diseases

Ian D Pavord et al. Allergy. 2022 Mar.

Abstract

Effective treatment of inflammatory diseases is often challenging owing to their heterogeneous pathophysiology. Understanding of the underlying disease mechanisms is improving and it is now clear that eosinophils play a complex pathophysiological role in a broad range of type 2 inflammatory diseases. Standard of care for these conditions often still includes oral corticosteroids (OCS) and/or cytotoxic immune therapies, which are associated with debilitating side effects. Selective, biological eosinophil-reducing agents provide treatment options that improve clinical symptoms associated with eosinophilic inflammation and reduce OCS use. Mepolizumab is a humanized monoclonal antibody that binds to and neutralizes interleukin-5, the major cytokine involved in eosinophil proliferation, activation, and survival. Mepolizumab is approved for the treatment of severe eosinophilic asthma, eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome. Additionally, the efficacy of add-on mepolizumab has been observed in patients with severe chronic rhinosinusitis with nasal polyposis and chronic obstructive pulmonary disease with an eosinophilic phenotype. Here, we review the development, approval, and real-world effectiveness of mepolizumab for the treatment of patients with severe eosinophilic asthma, from the DREAM to REALITI-A studies, and describe how knowledge from this journey extended to the use of mepolizumab and other biologics across a broad spectrum of eosinophilic diseases.

Keywords: clinical trials; eosinophilic diseases; interleukin-5; mepolizumab; real-world data.

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Conflict of interest statement

Ian Pavord reports that he has received speaker's honoraria for sponsored meetings from AstraZeneca, Boehringer Ingelheim, Aerocrine, Almirall, Novartis, Teva, Chiesi, Sanofi/Regeneron, and GSK; and payments for organizing educational events from AstraZeneca, GSK, Sanofi/Regeneron, and Teva. He has received honoraria for attending advisory panels with Genentech, Sanofi/Regeneron, AstraZeneca, Boehringer Ingelheim, GSK, Novartis, Teva, Merck, Circassia, Chiesi, and Knopp; and payments to support FDA approval meetings from GSK. He has received sponsorship to attend international scientific meetings from Boehringer Ingelheim, GSK, AstraZeneca, Teva, and Chiesi. He has received a grant from Chiesi to support a Phase II clinical trial in Oxford. He is co‐patent holder of the rights to the Leicester Cough Questionnaire; and has received payments for its use in clinical trials from Merck, Bayer, and Insmed. In 2014–15, he was an expert witness for a patent dispute involving AstraZeneca and Teva. Elisabeth H Bel reports grants from GSK and Teva; and personal fees from AstraZeneca, GSK, Sanofi/Regeneron, Sterna Biologicals, and Chiesi. Arnaud Bourdin has received grants from Boehringer Ingelheim and AstraZeneca; has participated in clinical research projects (as an investigator) with GSK, AstraZeneca, Boehringer Ingelheim, Chiesi, Novartis, and Sanofi; and has received personal fees from GSK, AstraZeneca, Regeneron‐Sanofi, Novartis, and Chiesi. Robert Chan, Oliver N Keene, Jonathan Steinfeld, and Steven W Yancey are employees of GSK and own stocks/shares. Neil Martin is a former employee of GSK and owns stocks and shares. Joseph K Han has received consultancy fees from Sanofi Genzyme, Regeneron, Genentech, Novartis, AstraZeneca, GSK, and Gossamer Bio. Mark C Liu reports funding for clinical trials or personal fees for advisory board participation from AstraZeneca, Boehringer Ingelheim, Gossamer Bio, GSK, and MedImmune. Alberto Papi has received grants, personal fees and non‐financial support and other from AstraZeneca, Teva, Mundipharma, GSK, Chiesi, and Boehringer Ingelheim; has received personal fees and non‐financial support from Novartis, Menarini, and Zambon; and has received grants from Sanofi. Florence Roufosse reports consultancy fees from AstraZeneca and GSK; and royalties from UpToDate. Michael E Wechsler has research grants with the National Institute of Allergy and Infectious Diseases and the National Heart, Lung, and Blood Institute and is a consultant with GSK, Genentech, Sanofi, Regeneron, AstraZeneca, Teva, Novartis, Boehringer Ingelheim, Sentien, and Equillium.

Figures

FIGURE 1
FIGURE 1
Sites of eosinophilic diseases. *Eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilic colitis. COPD, chronic obstructive pulmonary disease; EGPA, eosinophilic granulomatosis with polyangiitis; HES, hypereosinophilic syndrome
FIGURE 2
FIGURE 2
Mechanisms of action of anti‐IL‐5/anti‐IL‐5‐receptor antibodies. IL, interleukin
FIGURE 3
FIGURE 3
Timeline of the Phase III trials and approvals of mepolizumab in eosinophil‐driven diseases and the key takeaways. COPD, chronic obstructive pulmonary disease; CRSwNP, chronic rhinosinusitis with nasal polyposis; DREAM, Dose Ranging Efficacy And safety with Mepolizumab in severe asthma; EGPA, eosinophilic granulomatosis with polyangiitis; HES, hypereosinophilic syndrome; HRQoL, health‐related quality of life; ICS, inhaled corticosteroids; MATINEE, Mepolizumab as Add‐on Treatment IN participants with COPD characterized by frequent Exacerbations and Eosinophil level; MENSA, MEpolizumab as adjunctive therapy iN patients with Severe Asthma; METREO, MEpolizumab vs. placebo as add‐on TReatment for frequently exacerbating COPD patients characterized by EOsinophil level; METREX, MEpolizumab vs. placebo as add‐on TReatment for frequently EXacerbating COPD patients; MIRRA, Mepolizumab In Relapsing or Refractory EGPA; MUSCA, Mepolizumab adjUnctive therapy in subjects with Severe eosinophiliC Asthma; OCS, oral corticosteroids; REALITI‐A, REAL world effectiveness of mepolizumab In paTIent care—Asthma; SC, subcutaneous; SEA, severe eosinophilic asthma; SIRIUS, SteroId ReductIon with mepolizUmab Study; SYNAPSE, StudY in NAsal Polyps patients to assess the Safety and Efficacy of mepolizumab
See this image and copyright information in PMC

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