The Journal of allergy and clinical immunology | 2021
Novel antibody cocktail targeting Bet v 1 rapidly and sustainably treats birch allergy symptoms in a Phase 1 study.
Abstract
BACKGROUND\nThe 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.\n\n\nOBJECTIVE\nExtending these findings, we tested a Bet v 1-specific antibody cocktail in birch-allergic subjects.\n\n\nMETHODS\nPhase 1, randomized, double-blind, study: Part-A, ascending doses of Bet v 1-specific antibody cocktail REGN5713/14/15 (150-900 mg) in 32 healthy adults; Part-B, single subcutaneous 900 mg dose or placebo in 64 birch-allergic subjects. Total nasal symptom score (TNSS) response to titrated birch extract nasal allergen challenge (NAC) 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.\n\n\nRESULTS\nSingle dose REGN5713/14/15 significantly reduced TNSS following birch NAC relative to baseline. Differences in TNSS AUC(0-1 hr) versus 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 AUC of mean wheal diameters versus placebo (all P < .001) were sustained for ≥2 months; similar results observed with alder SPT. REGN5713/14/15 was well-tolerated. Basophil responsiveness to birch-related allergens was significantly decreased in REGN5713/14/15-treated subjects versus placebo on days 8, 57, and 113 (all P < .01).\n\n\nCONCLUSION\nSingle dose REGN5713/14/15 was well tolerated and provided a rapid (1 week) and durable (2 months) reduction in allergic symptoms after birch allergen NAC, potentially offering a new paradigm for the treatment of birch allergy symptoms.