Amgen and Kyowa Kirin Enter Global Collaboration to Develop and Commercialize KHK4083, a Potential First-in-Class Anti-OX40 Monoclonal Antibody for Atopic Dermatitis

On June 1, 2021, Amgen and Kyowa Kirin Co., Ltd. entered into a global exclusive licensing agreement to co-develop and commercialize KHK4083 for the treatment of atopic dermatitis and to explore its potential in other autoimmune diseases. KHK4083 is a potential first-in-class, fully human anti-OX40 monoclonal antibody, and a Phase 3 clinical trial is set to commence. In February this year, Kyowa Kirin announced positive results from a Phase 2 clinical trial of KHK4083 in patients with moderate-to-severe atopic dermatitis. This global collaboration will help advance the development of this innovative therapy across multiple inflammatory disease indications.

Under the terms of the agreement, Amgen will lead the development, manufacturing, and commercialization of KHK4083 in all markets outside Japan, while Kyowa Kirin will retain all rights for the Japanese market. Kyowa Kirin will receive a $400 million upfront payment and potential future milestone payments of up to $850 million, as well as royalties on future global sales. Amgen will also leverage the unique database of its subsidiary, deCODE genetics, to explore the potential use of KHK4083 in indications beyond atopic dermatitis.

OX40 (also known as CD134) is an important T cell co-stimulatory molecule and a member of the tumor necrosis factor receptor (TNFR) family. The signaling pathway it activates stimulates cytokine production, prolongs T cell survival, and inhibits the differentiation and activity of regulatory T cells (Tregs). OX40 is expressed on the surface of antigen-activated effector T cells, enhancing their cytotoxic activity.

KHK4083 is a fully humanized anti-OX40 monoclonal antibody developed by Kyowa Kirin, engineered with proprietary technology to enhance its antibody-dependent cell-mediated cytotoxicity (ADCC), and is currently in clinical trials for the treatment of indications such as ulcerative colitis and atopic dermatitis. KHK4083 has been demonstrated to selectively deplete activated T cells that are critical to the pathogenesis of atopic dermatitis.

▲ Mechanism of Action of KHK4083 (Image Source: Reference [1])

In February 2021, KHK4083 met its primary endpoint in a randomized, double-blind, placebo-controlled Phase 2 clinical trial involving 274 patients with moderate-to-severe atopic dermatitis. At week 16, improvements in the Eczema Area and Severity Index (EASI) were significantly greater in all treatment groups compared with the placebo group. Furthermore, the proportion of patients achieving an EASI-75 response (≥75% improvement in EASI score from baseline) or an IGA score of 0 or 1 (indicating complete or near-complete clearance of skin symptoms) at week 16 was significantly higher in the treatment groups than in the placebo group.

Atopic dermatitis is a severe chronic, relapsing skin disease associated with complex interactions between immune cells and inflammatory cytokines, wherein a dysregulated and overactive immune system triggers inflammation. Individuals with atopic dermatitis may develop rashes on any part of the body that can weep fluid and bleed when scratched. The skin becomes dry and thickened, making it more susceptible to infections. Moderate-to-severe atopic dermatitis is characterized by intense pruritus, leading to visible skin damage. Atopic dermatitis typically begins in childhood, affecting 15%–20% of children and 1%–3% of adults worldwide. Since the 1970s, the prevalence of this disease has increased two- to threefold, with over 30 million patients globally. Individuals with a personal or family history of asthma or hay fever are at a higher risk of developing atopic dermatitis.

Note: The original text has been abridged.

References:

[1] KHK4083 COLLABORATION WITH KYOWA KIRIN LUMAKRAS™ (SOTORASIB) APPROVAL. Retrieved June 1, 2021, from https://investors.amgen.com/static-files/5fa35df4-ff04-4a10-8574-5f6bd2820ae1

[2] Amgen and Kyowa Kirin to Jointly Develop and Commercialize KHK4083, a Phase 3-Ready, Potential First-In-Class Treatment for Atopic Dermatitis. Retrieved June 1, 2021, from https://www.amgen.com/newsroom/press-releases/2021/06/amgen-and-kyowa-kirin-to-jointly-develop-and-commercialize-khk4083-a-phase-3ready-potential-firstinclass-treatment-for-atopic-dermatitis

▽Follow 【WuXi KangGermany】WeChat Official Account