RATIONALE: Allergic conjunctivitis (AC) is an inflammatory disease characterized by extreme itching, pain, watering, redness and swelling of the conjunctiva. In severe cases, corneal damage and permanent vision loss can occur. Eosinophil recruitment and mast cell activation are key drivers of symptoms, and allergic comorbidities are common. Current treatments are often ineffective in severe AC and are associated with significant side effects. KRONOS evaluated the safety and preliminary efficacy of AK002, an anti-siglec-8 monoclonal antibody that depletes eosinophils and inhibits mast cells, in patients with severe AC. METHODS: This was a Ph1b open-label study of six monthly doses of AK002 in patients with atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC) and perennial allergic conjunctivitis (PAC) and history of topical or systemic corticosteroid use. Clinical activity was measured by a daily patient-reported allergic conjunctivitis symptom (ACS) questionnaire. Activity in allergic comorbidities was assessed by comparing pre-and post-treatment patient-reported symptom scores. RESULTS: Thirty patients were enrolled (AKC n513, VKC n51, PAC n516), 87% of whom had atopic comorbidities. By week 21-22 post-AK002,median ACS for AKC, VKC, and PAC groups improved by 74%, 87%, and 71%, respectively. There was substantial improvement in allergic comorbidities, with 65%, 72%, and 69% reduction of symptoms of atopic dermatitis, asthma, and rhinitis, respectively. There were no drug-related serious AEs, and the most common treatment-emergent AEs were mild-tomoderate infusion related reactions. CONCLUSIONS: AK002 was well-tolerated and substantially improved symptoms of severe AC. AK002 may be a promising treatment for severe AC as well as atopic dermatitis, asthma and other atopic conditions.
