• The study met its primary objective of demonstrating statistically greater improvement from baseline in Eczema Area and Severity Index score at 16 weeks versus placebo
  • Patients receiving KHK4083/AMG 451 showed statistically greater improvements in additional secondary efficacy endpoints versus placebo
  • KHK4083/AMG 451 also showed progressive improvement in efficacy beyond 16 weeks

TOKYO, Japan & THOUSAND OAKS, CA, USA I October 02, 2021 I Kyowa Kirin Co., Ltd. (TSE:4151) and Amgen (NASDAQ: AMGN) today announced that positive data from a Phase 2 study of KHK4083/AMG 451 were presented at the European Academy of Dermatology and Venereology 30th Virtual Congress on Oct. 2, 2021. KHK4083/AMG 451 is a potential first-in-class anti-OX40 fully human monoclonal antibody in development for the treatment of moderate-to-severe atopic dermatitis.

The Phase 2, multicenter, randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of KHK4083 / AMG 451 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 KHK4083/AMG 451 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%*; placebo = -15%).

All treatment groups of patients treated with KHK4083/AMG 451 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 KHK4083/AMG 451 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 KHK4083/AMG 451 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 KHK4083/AMG 451 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 over 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 KHK4043/AMG 451 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.”

* P<0.001 for KHK4083 vs placebo

About the KHK4083/AMG 451 Phase 2 Study
The Phase 2, multicenter, randomized, double-blind, placebo-controlled trial (NCT03703102) investigated the efficacy and safety of KHK4083/AMG 451 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 KHK4083/AMG 451 (600 mg Q2W, 600 mg Q4W, 300 mg Q2W or150 mg 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: https://www.eadvcongress2021.org/

Dr. Emma Guttman-Yassky is the leading investigator of the study and a paid consultant for the KHK4083/AMG 451 development by Kyowa Kirin.

About Atopic Dermatitis
Atopic dermatitis is a chronic inflammatory disease that causes excessively dry, itchy skin that can be painful. Repeated scratching can cause the skin to thicken, harden or become vulnerable to infection. Atopic dermatitis is the most common form of eczema – affecting 1-3% of adults worldwide – and the prevalence is increasing. The disease typically manifests in childhood followed by other allergy symptoms.

About KHK4083/AMG 451
KHK4083/AMG 451 is an anti-OX40 fully human monoclonal antibody engineered with Kyowa Kirin’s patented POTELLIGENT® defucosylation technology to enhance its antibody-dependent cellular cytotoxicity (ADCC) activity. The initial KHK4083/AMG 451 antibody was discovered in collaboration between Kyowa Kirin US Research and La Jolla Institute for Immunology .

KHK4083/AMG 451 targets and inhibits the activity of the OX40 receptor expressed on the surface of effector T-cells, and has been shown to enhance the depletion of activated OX40+ T-cells by ADCC. It has been reported that effector T cells expressing OX40 are present in the lesions of patients with atopic dermatitis and are critical in the disease pathophysiology.

Amgen and Kyowa Kirin Collaboration
On June 1, 2021, Kyowa Kirin and Amgen entered into an agreement to jointly develop and commercialize KHK4083/AMG 451. Under the terms of the agreement, Amgen will lead the development, manufacturing, and commercialization for KHK4083/AMG 451 for all markets globally, except Japan, where Kyowa Kirin will retain all rights. If approved, the companies will co-promote the asset in the United States and Kyowa Kirin has opt-in rights to co-promote in certain other markets including Europe and Asia.

About Kyowa Kirin
Kyowa Kirin strives to create and deliver novel medicines with life-changing value. As a Japan-based Global Specialty Pharmaceutical Company with a more than 70-year heritage, we apply cutting-edge science including expertise in antibody research and engineering, to address the needs of patients and society across multiple therapeutic areas including Nephrology, Oncology, Immunology/Allergy and Neurology. Across our four regions – Japan, Asia Pacific, North America and EMEA/International – we focus on our purpose, to make people smile, and are united by our shared values of commitment to life, teamwork/Wa, innovation, and integrity. You can learn more about the business of Kyowa Kirin at: https://www.kyowakirin.com/.

About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people’s lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world’s leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.

For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.