1. Novel antibody cocktail targeting Bet v 1 rapidly and sustainably treats birch allergy symptoms in a phase 1 study
- Author
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Jamie M. Orengo, Sylvie Rottey, Natalie De Ruyck, Amanda Atanasio, Lorah Perlee, Meagan P. O'Brien, Jan de Hoon, Divya Ramesh, Bram Volckaert, Kristof Lesneuck, Hisham Abdallah, Mohamed A. Kamal, David M. Weinreich, Jarno De Craemer, Michelle DeVeaux, George D. Yancopoulos, Claire Q. Wang, Philippe Gevaert, Gary Herman, Robert Dingman, Peter Hellings, Vishal Kamat, and Ear, Nose and Throat
- Subjects
Male ,Allergy ,medicine.disease_cause ,Gastroenterology ,ACTIVATION ,Allergen ,Medicine ,Immunology and Allergy ,HYPERSENSITIVITY ,Betula ,Allergen immunotherapy ,Area under the curve ,Antibodies, Monoclonal ,Middle Aged ,Basophils ,Peak Nasal Inspiratory Flow ,Female ,monoclonal antibodies ,Adult ,medicine.medical_specialty ,Immunology ,APPLE ALLERGY ,Placebo ,Young Adult ,Oral allergy syndrome ,Double-Blind Method ,BET-V-1 ,Internal medicine ,Bet v 1 ,otorhinolaryngologic diseases ,Humans ,biologics ,IGE ,HUMANIZATION ,allergic rhinitis ,POLLEN IMMUNOTHERAPY ,business.industry ,Biology and Life Sciences ,RHINITIS ,Rhinitis, Allergic, Seasonal ,Allergens ,Antigens, Plant ,medicine.disease ,EFFICACY ,LONG ,Basophil activation ,Desensitization, Immunologic ,Immunoglobulin G ,allergen immunotherapy ,birch allergy ,business - 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. ispartof: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY vol:149 issue:1 pages:189-199 ispartof: location:United States status: published
- Published
- 2021