Rationale: Sensitization to Fel d 1 (Felis domesticus
allergen 1) contributes to persistent
allergic rhinitis and
asthma. Existing treatment options for cat
allergy, including allergen immunotherapy, are only moderately effective, and allergen immunotherapy has limited use because of safety concerns. Objectives: To explore the relationship among the pharmacokinetic, clinical, and immunological effects of anti-Fel d 1
monoclonal antibodies (REGN1908-1909) in patients
after treatment. Methods: Patients received REGN1908-1909 (n = 36) or a placebo (n = 37) in a phase 1b study. Fel d 1-induced basophil and
IgE-facilitated
allergen binding responses were evaluated at baseline and Days 8, 29, and 85.
Cytokine and
chemokine concentrations in nasal fluids were measured, and REGN1908-1909 inhibition of
allergen-
IgE binding in patient serum was evaluated. Measurements and Main Results: Peak serum drug concentrations were concordant with maximal observed clinical response. The anti-Fel d 1
IgE/cat dander
IgE ratio in pretreatment serum correlated with Total Nasal Symptom Score improvement. The
allergen-neutralizing capacity of REGN1908-1909 was observed in serum and nasal fluid and was detected in an inhibition assay. Type 2
cytokines (IL-4, IL-5, and IL-13) and
chemokines (CCL17/TARC, CCL5/
RANTES [regulated upon activation, normal T-cell expressed and secreted]) in nasal fluid were inhibited in REGN1908-1909-treated patients compared with placebo (P < 0.05 for all);
IL-13 and
IL-5 concentrations correlated with Total Nasal Symptom Score improvement. Ex vivo assays demonstrated that REGN1908 and REGN1909 combined were more potent than each alone for inhibiting FcεRI- and FcεRII (CD23)-mediated allergic responses and subsequent T-cell activation. Conclusions: A single, passive-dose administration of Fel d 1-neutralizing
IgG antibodies improved nasal symptoms in cat-allergic patients and was underscored by suppression of FcεRI-, FcεRII-, and T-helper cell type 2-mediated allergic responses. Clinical trial registered with www.clinicaltrials.gov (NCT02127801).