VTX-1463, a novel TLR8 agonist for the treatment of allergic rhinitis.

INTRODUCTION: Allergic rhinitis significantly impacts quality of life and current treatments are frequently unsatisfying. VTX-1463 is a potent, selective, Toll-like receptor (TLR) 8 agonist administered weekly via the intranasal route without concomitant administration of allergen for the treatment of allergic rhinitis. AREAS COVERED: The rationale for TLR8 as a therapeutic target in allergic disease is summarized. The potency of VTX-1463 for TLR8 is outlined, and preclinical efficacy data from a ragweed-sensitized beagle dog model of allergic rhinitis are reviewed. Results of three randomized, double-blind, placebo-controlled trials with VTX-1463 are also reviewed: (i) a first-in-man study in healthy volunteers, (ii) an allergen challenge study in atopic individuals out of pollen seasons and (iii) an allergen challenge study in atopic individuals during season. EXPERT OPINION: Two or four weekly pretreatments with VTX-1463 in subjects with grass pollen allergies provided statistically significant improvement in nasal symptoms, as measured by total nasal symptom score (TNSS) and active anterior rhinomanometry (AAR), while subjects were exposed to grass pollen in the Vienna Challenge Chamber (VCC). Improvement in nasal secretion weights and ocular symptom scores was also observed. VTX-1463 is a promising new agent for the treatment of seasonal, and potentially perennial, allergic rhinitis.