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Novel antibody cocktail targeting Bet v 1 rapidly and sustainably treats birch allergy symptoms in a phase 1 study - 05/01/22

Doi : 10.1016/j.jaci.2021.05.039 
Philippe Gevaert, MD, PhD a, , Jarno De Craemer, MD a, , Natalie De Ruyck, MS a, Sylvie Rottey, MD, PhD b, Jan de Hoon, MD, PhD c, Peter W. Hellings, MD a, d, e, Bram Volckaert, MD f, Kristof Lesneuck, MS f, Jamie M. Orengo, PhD g, Amanda Atanasio, MS g, Mohamed A. Kamal, PhD g, Hisham Abdallah, PhD g, Vishal Kamat, PhD g, Robert Dingman, PhD g, Michelle DeVeaux, PhD g, Divya Ramesh, PhD g, Lorah Perlee, PhD g, Claire Q. Wang, PhD g, David M. Weinreich, MD g, Gary Herman, MD g, George D. Yancopoulos, MD, PhD g, Meagan P. O’Brien, MD g,
a Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium 
b Drug Research Unit Ghent, Ghent University Hospital, Ghent, Belgium 
c Center for Clinical Pharmacology, UZ Leuven, Leuven, Belgium 
d Allergy and Clinical Immunology Research Group, KU Leuven, Leuven, Belgium 
e Academic Medical Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands 
f SGS Belgium Clinical Pharmacology Unit Antwerpen, Antwerp, Belgium 
g Regeneron Pharmaceuticals, Inc, Tarrytown, NY 

Corresponding author: Meagan P. O’Brien, MD, Regeneron Pharmaceuticals, Inc, 777 Old Saw Mill River Road, Tarrytown, NY 10591.Regeneron Pharmaceuticals, Inc777 Old Saw Mill River RoadTarrytownNY10591

Abstract

Background

The efficacy of an allergen-specific IgG cocktail to treat cat allergy suggests that allergen-specific IgG may be a major protective mechanism elicited by allergen immunotherapy.

Objectives

Extending these findings, we tested a Bet v 1–specific antibody cocktail in birch-allergic subjects.

Methods

This was a phase 1, randomized, double-blind, study with 2 parts. Part A administered ascending doses of the Bet v 1–specific antibody cocktail REGN5713/14/15 (150-900 mg) in 32 healthy adults. Part B administered a single subcutaneous 900-mg dose or placebo in 64 birch-allergic subjects. Total nasal symptom score response to titrated birch extract nasal allergen challenge and skin prick test (SPT) with birch and alder allergen were assessed at screening and days 8, 29, 57, and 113 (SPT only); basophil activation tests (n = 26) were conducted.

Results

Single-dose REGN5713/14/15 significantly reduced total nasal symptom score following birch nasal allergen challenge relative to baseline. Differences in total nasal symptom score areas under the curve (0-1 hour) for subjects treated with REGN5713/14/15 versus those given placebo (day 8: −1.17, P = .001; day 29: −1.18, P = .001; day 57: −0.85, P = .024) and titration SPT with birch difference in area under the curve of mean wheal diameters for subjects treated with REGN5713/14/15 versus placebo (all P < .001) were sustained for ≥2 months; similar results were observed with alder SPT. REGN5713/14/15 was well tolerated. Basophil responsiveness to birch-related allergens was significantly decreased in subjects treated with REGN5713/14/15 versus those given placebo on days 8, 57, and 113 (all P < .01).

Conclusions

Single-dose REGN5713/14/15 was well tolerated and provided a rapid (1 week) and durable (2 months) reduction in allergic symptoms after birch allergen nasal allergen challenge, potentially offering a new paradigm for the treatment of birch allergy symptoms.

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Graphical abstract




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Key words : Allergen immunotherapy, monoclonal antibodies, biologics, allergic rhinitis, Bet v 1, birch allergy

Abbreviations used : AIT, AR, AUC, BAT, EC50, NAC, OAS, PNIF, SPT, TEAE, TNSS, TOSS


Plan


 Clinical Trials Registration: Study to Assess the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Effects of a Single Dose of REGN5713-5714-5715 in Healthy Adult Participants (NCT03969849). Registered May 31, 2019. NCT03969849.
 This study was funded by Regeneron Pharmaceuticals, Inc.
 Disclosure of potential conflict of interest: P. Gevaert has received consulting fees, honoraria for lectures, and/or research funding from Stallergenes Greer, 3NT, Ablynx, ALK, Argenx, AstraZeneca, Bekaert Textiles, Genentech, Hall Allergy, Medtronic, Novartis, Regeneron Pharmaceuticals, Inc., Roche, Sanofi-Genzyme, Teva, and Thermo Fisher. J. De Craemer has received research funding from Argenx and Regeneron Pharmaceuticals, Inc. N. De Ruyck has received research funding from Argenx and Regeneron Pharmaceuticals, Inc. S. Rottey has received research funding from Merck, Sharp, and Dohme and Roche. J. de Hoon, B. Volckaert, and K. Lesneuck were all principal investigators of this 1857 trial. P. Hellings has received unrestricted research grants from Mylan and GlaxoSmithKline; and lecture fees from Stallergenes and ALK. J. Orengo, A. Atanasio, M. Kamal, H. Abdallah, V. Kamat, R. Dingman, M. DeVeaux, D. Ramesh, L. Perlee, C. Q. Wang, D. Weinreich, G. Herman, G. D. Yancopoulos, and M. P. O’Brien are employees of and stakeholders in Regeneron Pharmaceuticals, Inc.


© 2021  The Authors. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 149 - N° 1

P. 189-199 - janvier 2022 Retour au numéro
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