HAMILTON, Bermuda—Kiniksa Pharmaceuticals Ltd., a biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutic medicines for patients with significant unmet medical need, presented Phase 1a/1b clinical data for a first-in-human study of its KPL-716 monoclonal antibody at the 27th European Academy of Dermatology and Venereology (EADV) Congress. Dr. Zamaneh Mikhak, senior director of clinical research and development at Kiniksa, delivered an oral presentation entitled “First-In-Human Study of KPL-716, Anti-Oncostatin M Receptor Beta Monoclonal Antibody, in Healthy Volunteers and Subjects with Atopic Dermatitis” during the late-breaking news session of the conference.
KPL-716 “targets oncostatin M receptor beta (OSMRβ), which mediates signaling of IL-31 and oncostatin M (OSM), two key cytokines implicated in pruritus, inflammation and fibrosis,” according to Kiniksa. The company believes that KPL-716 is the only monoclonal antibody in development that targets both pathways at the same time.
Single intravenous (IV) and subcutaneous (SC) doses of the investigational fully human monoclonal antibody were well tolerated in both adult healthy volunteers and adult subjects with moderate-to-severe atopic dermatitis experiencing moderate-to-severe pruritus. KPL-716 also demonstrated a reduction in pruritus, itching that can be associated with a number of disorders, including dry skin, skin disease, pregnancy and, rarely, cancer. Thanks to these findings, Kiniksa will expand clinical development into multiple chronic pruritic diseases, including prurigo nodularis.
According to Dr. John F. Paolini, chief medical officer of Kiniksa, “The KPL-716 Phase 1a/1b results met a high hurdle for success, as the placebo-controlled, single-dose safety and pharmacokinetics study also demonstrated reduction in pruritus. We are now considering advancement of KPL-716 into multiple chronic pruritic diseases, including prurigo nodularis. Additionally, the observed reduction in Eczema Area and Severity Index scores after only a single dose of KPL-716 is encouraging. Our ongoing repeat-single-dose trial in atopic dermatitis subjects will provide longer-term exposures and data on these inflammatory disease response markers.”
The clinical trial used a double-blind, randomized, placebo-controlled, single-ascending-dose, sequential-group design to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of KPL-716 in healthy volunteers and subjects with atopic dermatitis following IV or SC administration. Atopic dermatitis was used as a proxy for IL-31-driven pruritic diseases, including prurigo nodularis.
Fifty healthy volunteers and 32 subjects with moderate-to-severe atopic dermatitis who had moderate-to-severe pruritus got a single dose of KPL-716 or placebo in the clinical trial, with the top dose of 20 mg/kg IV in healthy volunteers and 7.5 mg/kg IV in subjects with atopic dermatitis. The study had a seven-day wash out period of prior therapies for all subjects with atopic dermatitis before treatment, and topical corticosteroids (TCS) were not permitted through day 28. All subjects were given TCS to use as needed after day 28, and rescue medication was made available for atopic dermatitis flares throughout the study.
KPL-716 appeared to be well tolerated by all subjects. There were no dose-limiting toxicities observed, and no serious adverse events. The monoclonal antibody demonstrated dose-dependent elimination consistent with a target-mediated drug disposition profile, and was still detectable at least eight weeks after the high dose of 7.5 mg/kg IV in subjects with atopic dermatitis. Pharmacokinetic and bioavailability data appear to support SC dosing regimens to be tested in subsequent studies of a single injection once every other week or once a month. A single dose of KPL-716 7.5 mg/kg IV in subjects with moderate-to-severe atopic dermatitis as opposed to pooled placebo IV recipients showed evidence of target engagement and an early signal of efficacy for KPL-716 in reducing pruritus. Patients reported less itching, the effect was persistent and there was less sleep loss.