2. Academic Validation
  3. Novel antibody cocktail targeting Bet v 1 rapidly and sustainably treats birch allergy symptoms in a phase 1 study

Novel antibody cocktail targeting Bet v 1 rapidly and sustainably treats birch allergy symptoms in a phase 1 study

  • J Allergy Clin Immunol. 2022 Jan;149(1):189-199. doi: 10.1016/j.jaci.2021.05.039.
Philippe Gevaert 1,  Jarno De Craemer 1,  Natalie De Ruyck 1,  Sylvie Rottey 2,  Jan de Hoon 3,  Peter W Hellings 4,  Bram Volckaert 5,  Kristof Lesneuck 5,  Jamie M Orengo 6,  Amanda Atanasio 6,  Mohamed A Kamal 6,  Hisham Abdallah 6,  Vishal Kamat 6,  Robert Dingman 6,  Michelle DeVeaux 6,  Divya Ramesh 6,  Lorah Perlee 6,  Claire Q Wang 6,  David M Weinreich 6,  Gary Herman 6,  George D Yancopoulos 6,  Meagan P O'Brien 7
Affiliations

Affiliations

  • 1 Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium.
  • 2 Drug Research Unit Ghent, Ghent University Hospital, Ghent, Belgium.
  • 3 Center for Clinical Pharmacology, UZ Leuven, Leuven, Belgium.
  • 4 Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium; Allergy and Clinical Immunology Research Group, KU Leuven, Leuven, Belgium; Academic Medical Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands.
  • 5 SGS Belgium Clinical Pharmacology Unit Antwerpen, Antwerp, Belgium.
  • 6 Regeneron Pharmaceuticals, Inc, Tarrytown, NY.
  • 7 Regeneron Pharmaceuticals, Inc, Tarrytown, NY. Electronic address: [email protected].
PMID: 34126156 DOI: 10.1016/j.jaci.2021.05.039
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.

Keywords

Allergen immunotherapy; Bet v 1; allergic rhinitis; biologics; birch allergy; monoclonal antibodies.

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