Amgen (NASDAQ: AMGN) and Kyowa Kirin Co., Ltd. (TSE:4151) today announced that positive data from a Phase 2 study of AMG 451/KHK4083 were presented at the European Academy of Dermatology and Venereology 30th Virtual Congress on Oct. 2, 2021. AMG 451/KHK4083 is a potential first-in-class anti-OX40 fully human monoclonal antibody in development for the treatment of moderate-to-severe atopic dermatitis.
Kyowa Kirin Logo (PRNewsfoto/Amgen)
Kyowa Kirin Logo (PRNewsfoto/Amgen)
The Phase 2, multicenter, randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of AMG 451/KHK4083 in adults with moderate-to-severe atopic dermatitis who were not adequately controlled with topical agents. The study met the primary objective, showing statistically greater improvements from baseline in Eczema Area and Severity Index (EASI) score at 16 weeks with all four subcutaneous doses of AMG 451/KHK4083 compared with placebo (600 mg every two weeks (Q2W) = -57.4%; 600 mg Q4W = -49.7%; 300 mg Q2W = -61.1%; 150 mg Q4W = -48.3% vs. placebo = -15%; P<0.001).
All treatment groups of patients receiving AMG 451/KHK4083 generally achieved improvements compared to placebo at week 16 for key secondary endpoints, such as achieving at least a 75% reduction from baseline in EASI score (EASI-75), an Investigator Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with at least 2-point reduction from baseline (IGA 0/1) and at least a 4-point reduction from baseline in pruritus Numerical Rating Scale (NRS) score (PNRS-4). Efficacy measures continued to improve after week 16 for all AMG 451/KHK4083 doses.
The most commonly reported adverse events that occurred in at least 5% of patients were pyrexia, nasopharyngitis, worsening of atopic dermatitis and chills. The events of pyrexia and chills were mild to moderate in intensity and did not lead to treatment discontinuations.
“The Phase 2 results are both positive and exciting. They show improvement across all 4 dose groups compared to placebo, and highlight the potential of OX40 antagonism to help patients,” said the lead investigator of this study, Dr. Emma Guttman-Yassky, MD./PhD., system chair for the Department of Dermatology and Waldman Professor of Dermatology and Immunology, Icahn School of Medicine at Mount Sinai and Director of the Center for Excellence in Eczema, and the Laboratory of Inflammatory Skin Diseases at Mount Sinai. “I hope that future clinical development data will further elucidate the significance and potential of AMG 451/KHK4083 in the treatment of moderate-to-severe atopic dermatitis.”
“We are very pleased to present data from our Phase 2 study assessing the efficacy and safety of AMG 451/KHK4083 in chronic, recurrent, moderate-to-severe atopic dermatitis at the EADV congress,” said Yoshifumi Torii, Ph.D., executive officer, vice president, head of R&D Division of Kyowa Kirin. “The results show inhibition and deletion of the OX40-expressing cells may provide an important new approach to treating moderate-to-severe atopic dermatitis, with the potential to help patients maintain responses.”
“Atopic dermatitis affects nearly 30 million people a year and is known to have an extremely negative impact on patients’ lives,” said David M. Reese, M.D., executive vice president of Research and Development at Amgen. “These data provide strong evidence of the potential of AMG 451/KHK4083 for patients, and we look forward to studying this treatment further in Phase 3 clinical trials, which we expect to begin in the first half of 2022.”
About the AMG 451/KHK4083 Phase 2 Study
The Phase 2, multicenter, randomized, double-blind, placebo-controlled trial (NCT03703102) investigated the efficacy and safety of AMG 451/KHK4083 in adults with moderate-to-severe atopic dermatitis who were not adequately controlled with topical agents. The study randomized 274 patients in the U.S., Japan, Canada and Germany across four dose-ranging active treatment groups, which received subcutaneous AMG 451/KHK4083 (600mg Q2W, 600mg Q4W, 300mg Q2W, 150mg Q4W), and a comparator placebo arm.
The primary endpoint was percentage change from baseline in EASI score at week 16. Additional endpoints include achievement of ≥75% reduction (improvement) from baseline in EASI score, IGA score of 0 (clear) or 1 (almost clear) with ≥ 2 points reduction from baseline, and ≥ 4 points reduction from baseline in the pruritus numeric rating scale (NRS) score. Patients in the study were followed up to week 56.
The presentation slides are available on the EADV website:
Dr. Emma Guttman-Yassky is the lead investigator of the study and a paid consultant for the AMG 451/KHK4083 development by Kyowa Kirin.
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