Kyowa Kirin Announces Positive Phase 2 Results for First-in-Class Anti-OX40 Monoclonal Antibody KHK4083 in Moderate to Severe Atopic Dermatitis

February 19, 2021 /Bio ValleyBIOON/ -- Japanese pharmaceutical company Kyowa Kirin recently announced that its Phase 2 study evaluating the antibody drug KHK4083 for the treatment of adult patients with moderate-to-severe atopic dermatitis (AD) had met its primary endpoint.

KHK4083 is a potential first-in-class fully human monoclonal antibody against OX40, currently under development for the treatment ofAutoimmunityinflammatory diseases, including atopic dermatitis (AD). KHK4083 was discovered by Kyowa Kirin and is manufactured using the company’s patented POTELLIGENT® defucosylation technology to enhance its antibody-dependent cellular cytotoxicity (ADCC) activity. The combined effects of ADCC and OX40 antagonism may suppress the inflammatory response that underlies atopic dermatitis.

OX40 is a costimulatory molecule, which isTumorMembers of the tumor necrosis factor receptor (TNFR) superfamily play a crucial role in maintaining T cell proliferation and survival, as well as in the formation of memory T cells. OX40 is expressed on the surface of antigen-activated effector T cells (CD4-positive). It has been reported that OX40-expressing effector T cells are present in the skin lesions of atopic dermatitis.

Atopic Dermatitis (Image Source: icresearch.net)

This Phase 2 study was a multicenter, randomized, double-blind, placebo-controlled clinical trial conducted in Japan, the United States, Canada, and Germany, designed to evaluate the efficacy and safety of KHK4083. A total of 274 patients with moderate-to-severe atopic dermatitis, whose disease was not adequately controlled with topical therapy, were enrolled in the study.

In this study, all KHK4083 cohorts met the primary endpoint: they demonstrated statistically significant superiority over the placebo cohort in terms of the percent change from baseline in the Eczema Area and Severity Index (EASI) at Week 16. Furthermore, all KHK4083 cohorts showed significant differences compared to the placebo cohort in the proportion of patients achieving an EASI-75 response (≥75% improvement in EASI score from baseline) at Week 16, as well as in the proportion of patients achieving an Investigator’s Global Assessment (IGA) score of 0 or 1 with an improvement of ≥2 points from baseline at Week 16. Beyond Week 16, further improvements in the efficacy of KHK4083 were observed. Common treatment-emergent adverse events (TEAEs) in the KHK4083 cohorts included fever, nasopharyngitis, exacerbation of atopic dermatitis, and chills occurring within the first 16 weeks. The intensity of fever and chills was mild to moderate, mostly attributed to injection reactions, and observed only after the first administration of the investigational product. No cases of severe allergic reactions or deaths were observed during the study.

The full results of this study will be presented at a future medicalMeetingpublished above. The study’s principal investigator, Chair of the Department of Dermatology at the Icahn School of Medicine and Professor of Dermatology andImmunologyProfessor Emma Guttman-Yassky, MD, stated: “The phase 2 study results of KHK4083 indicate that OX40 is a relevant target in atopic dermatitis and may offer a novel therapeutic modality. In addition to the primary endpoint, the study demonstrated progressive improvement in efficacy with continued KHK4083 treatment beyond 16 weeks, and the potential for sustained long-term therapeutic effects after completion of KHK4083 therapy.”(Bioon.com)

Original Source: Kyowa Kirin Announces Positive Phase 2 Results for KHK4083 in Patients with Moderate to Severe Atopic Dermatitis