A Phase 1 study of the long‐acting anti‐IL‐5 monoclonal antibody GSK3511294 in patients with asthma

Abstract

Max word count; current word count: 4000; 3988No. tables/figures: 5 (3 tables, 2 figures) Principal Investigator statementThe authors confirm that the PI for this paper is Dave Singh and that he had direct clinical responsibility for patients. Data availability statementAnonymized individual participant data and study documents can be requested for further research from www.clinicalstudydatarequest.com. The trial protocol is available at https://www.gsk-studyregister.com/en/ Funding sources and roleThis study was funded by GlaxoSmithKline (GSK ID 205722; NCT03287310) Authors contributionsAll authors reviewed and revised the manuscript, approved the final version, and made the decision to submit the manuscript for publication. Additionally, SM, IJP and NPB were involved in the conception and design of the study, DS and RF were involved in the acquisition of the data, and IJP, KH, YLM, NPB, SWY and AC were involved in the data analysis and interpretation.

Investigational Treatments in Phase I and II Clinical Trials: A Systematic Review in Asthma

“…Study results for seven RCTs [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ] were retrieved from ClinicalTrials.gov, results for five RCTs [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ] were published in full text articles, and data for two RCTs [ 40 , 41 , 42 , 43 ] were obtained through the European Union (EU) Clinical Trial Register. Results for two RCTs [ 44 , 45 , 46 , 47 ] were available only from conference abstracts or posters, data for one RCT [ 48 , 49 , 50 ] were retrieved from both the EU Clinical Trial Register and abstract, and for another RCT, they were retrieved from both ClinicalTrials.gov and the abstract [ 51 , 52 ].…”

“…Targeting BEC reduction through the inhibition of IL-5 represents an established therapeutic option in severe asthma [ 57 ]. Depemokimab (GSK3511294) is a subcutaneously administered anti-IL-5 mAb, designed for improved affinity and long-acting IL-5 suppression compared to the currently approved anti-IL-5 mAbs, and it has been evaluated in a first-in-human Phase I RCT [ 30 , 31 ] enrolling mild to moderate asthmatic patients with BEC ≥ 200 cells/μL at screening.…”

“…A single administration of depemokimab generally improved lung function parameters with an increase in the dose from 2 mg to 300 mg. Depemokimab 300 mg induced a greater improvement from baseline in FEV 1 (240 mL (95%CI 68–412)) vs. PCB (105 mL (95%CI not calculated)) and in percent predicted normal FEV 1 (7.65% (95%CI 1.76–13.54)) vs. PCB (3.85% (95%CI not calculated)). No data are available for symptoms control [ 30 , 31 ].…”

“…The duration of such marked suppression of BEC was dose dependent, and thus was maintained for longer with the increasing dose. Six months after the single-dose administration, depemokimab induced reductions in BEC of 31.0% (2 mg), 41.0% (10 mg), 72.0% (30 mg), 82.0% (100 mg), and 83.0% (300 mg) vs. PCB [ 30 , 31 ].…”

Preclinical development of a long-acting trivalent bispecific nanobody targeting IL-5 for the treatment of eosinophilic asthma

“…Unlike antibodies that target IL-5, benralizumab reduces eosinophils more efficiently via antibody-dependent cell-mediated cytotoxicity, resulting in the improvement of lung function or asthma control [ 16 ]. In addition, GSK3511294, another IL-5 mAb, with the same antigen-binding epitope as mepolizumab, but with higher affinity and longer half-life, is currently in phase 3 clinical investigation for the treatment of severe eosinophilic asthma [ 17 ]. These findings suggest that biologics targeting IL-5/IL-5R with less frequent dosing, higher tissue penetration, and novel mechanisms of action remain needed for the treatment of severe eosinophilic asthma.…”