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. 2024 Sep 23;10(5):00718-2023.
doi: 10.1183/23120541.00718-2023. eCollection 2024 Sep.

AERIFY-1/2: two phase 3, randomised, controlled trials of itepekimab in former smokers with moderate-to-severe COPD

Klaus F Rabe  1   2   3 , Fernando J Martinez  4 , Surya P Bhatt  5 , Tomotaka Kawayama  6 , Borja G Cosio  7 , Robert M Mroz  8 , Maarten M Boomsma  9 , Helene Goulaouic  10 , Michael C Nivens  11 , Michel Djandji  12 , Xavier Soler  11 , Ying Liu  13 , Matthew P Kosloski  11 , Christine R Xu  13 , Nikhil Amin  11 , Heribert Staudinger  13 , David J Lederer  11 , Raolat M Abdulai  14
Affiliations

AERIFY-1/2: two phase 3, randomised, controlled trials of itepekimab in former smokers with moderate-to-severe COPD

Klaus F Rabe et al. ERJ Open Res. .

Abstract

Background: Accumulating data implicate interleukin (IL)-33, a proinflammatory cytokine released locally upon epithelial cell damage, in the pathogenesis of COPD. In a phase 2 study, itepekimab, a human monoclonal antibody against IL-33, reduced exacerbations and improved lung function in a subgroup analysis of former smokers with COPD with an acceptable safety profile.

Methods: The study designs of AERIFY-1 and AERIFY-2 are described in this article.

Discussion: The primary objective of AERIFY-1/2 (NCT04701983/NCT04751487), two phase 3 randomised, double-blind, placebo-controlled trials, is to assess the efficacy and safety of itepekimab versus placebo in a population of former smokers with moderate-to-severe COPD over up to 52 weeks. An additional secondary population of current smokers are being enrolled in AERIFY-2. These two studies will enrol patients (aged 40-85 years) with COPD and chronic bronchitis who had ≥2 moderate or ≥ 1 severe exacerbations within the previous year despite standard-of-care triple or double background therapy. All participants are required to have ≥10-pack-year smoking history, and ≥6 months since smoking cessation for former smokers. The primary end-point is the annualised rate of moderate or severe acute exacerbation of COPD. Secondary end-points include change from baseline in pre- and post-bronchodilator forced expiratory volume in 1 s, and annualised frequency of severe exacerbations. Symptomatic end-points include Evaluating Respiratory Symptoms in COPD and St. George's Respiratory Questionnaire, safety and anti-drug antibody responses.

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Conflict of interest statement

Conflict of interest: K.F. Rabe reports consultancy, speaker fees’ and advisory board membership for AstraZeneca, Boehringer Ingelheim, Chiesi, Gilead, GSK, Novartis, Pearl, Sanof and Teva; and is cofounder of rnatics, Germany. Conflict of interest: F.J. Martinez has been on steering committees for Afferent/Merck, AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, GlaxoSmithKline, Nitto Pharma, Patara Pharma/Respivant Sciences, Pearl Pharmaceuticals, ProMedior/Roche, ProMetic Life Sciences, Stromedix/Biogen and Veracyte; has been an advisory board member for AstraZeneca, BioScale/ProTerrix Bio, Boehringer Ingelheim, Chiesi, CSL Behring, Gala Therapeutics, Genentech, GlaxoSmithKline, Novartis, Pearl Pharmaceuticals, Physicians Education Resource, Sunovion, Teva and Zambon; has been a consultant for Bridge Biotherapeutics, Bristol Myers Squibb and twoXR; reports continuing medical education presentation support from the Canadian Respiratory Network, Chiesi, CME Outfitters, Dartmouth University, France Foundation, Inova Fairfax, MD Magazine, Methodist Hospital, Miller Communications, National Association for Continuing Education/Haymarket, New York University, PeerView, Prime Education, Rare Diseases Healthcare Communication, Rockpointe, University of Alabama at Birmingham, UpToDate, Vindico Pharmaceuticals, WebMD/MedScape and Zambon; and has been on the data and safety monitoring board for Boehringer Ingelheim and GlaxoSmithKline. Conflict of interest: S.P. Bhatt has served on advisory boards for Boehringer Ingelheim and Regeneron, received consulting fees from Sanofi, and reports fees for continuing medical education from IntegrityCE. Conflict of interest: T. Kawayama reports support from GSK, AstraZeneca, Novartis Pharma and Healios. Conflict of interest: B.G. Cosio has served as a consultant and received speaker fees from AstraZeneca, Boehringer Ingelheim, Novartis, Chiesi, Menarini, GSK, Sanofi and Teva. Conflict of interest: R.M. Mroz reports support from AstraZeneca, Boehringer Ingelheim, Chiesi, Genentech, MSD, Gilead, GSK, Novartis, Pearl Pharmaceuticals, Sanofi and Teva. Conflict of interest: M.M. Boomsma, H. Goulaouic, M. Djandji, Y. Liu, C.R. Xu and H. Staudinger are Sanofi employees and may hold stock and/or stock options in the company. Conflict of interest: M.C. Nivens, X. Soler, M.P. Kosloski and D.J. Lederer are Regeneron Pharmaceuticals Inc. employees and shareholders. Conflict of interest: N. Amin is a prior employee and shareholder for Regeneron Pharmaceuticals Inc. Conflict of interest: R.M. Abdulai is a prior employee and stock holder for Sanofi.

Figures

FIGURE 1
FIGURE 1
Itepekimab, a novel fully human anti-IL-33 monoclonal antibody, blocks the effects of IL-33, an alarmin implicated in type 1 and type 2 inflammation in COPD. IL: interleukin; Th: T helper; IFN: interferon; EGF: epidermal growth factor; TGF: transforming growth factor; TNF: tumour necrosis factor.
FIGURE 2
FIGURE 2
Itepekimab phase 3 study design: a) AERIFY-1; b) AERIFY-2. R: randomisation; SC: subcutaneous; q2w: every 2 weeks; q4w: every 4 weeks.
FIGURE 3
FIGURE 3
Current evidence for differential treatment effects between former and current smokers with COPD. BD: bronchodilator; CXCL2: chemokine (C-X-C motif) ligand 2; FEV1: forced expiratory volume in 1 s; ICS: inhaled corticosteroids; IL: interleukin; LABA: long-acting β2-agonist; LAMA: long-acting muscarinic antagonist. #: results from ICS/LABA of former smokers versus placebo compared with ICS/LABA of current smokers versus placebo. : no p-value was reported.
See this image and copyright information in PMC

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