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OX40 receptor (OX40) and its ligand (OX40L) are crucial proteins involved in human adaptive immune responses. OX40 acts as a costimulatory molecule, enhancing T cell activation, differentiation, and survival when bound to OX40L. This interaction is significant in various inflammatory skin conditions, such as atopic dermatitis (AD), where T cells play a pivotal role in disease pathogenesis.1

Previously, Dermatology Times reported on several clinical studies and conference presentations surrounding the use of OX40 for AD. Most recently, James Song, MD, FAAD, chief medical officer and director of clinical research at Frontier Dermatology in Seattle, Washington, delved into the complexities and advancements in treating AD on an episode of Dermatology Times’ podcast series The Cutaneous Connection. Song talked about exploring patient-specific factors in treatment choices, the importance of systemic therapy for moderate to severe cases, and the promise of emerging biologics targeting IL-31 and OX40 pathways.²

On a similar topic, Dermatology Times interviewed Melinda Gooderham, MSc, MD, FRCPC, on her presentation at the Revolutionizing Alopecia Areata, Vitiligo, and Eczema conference in Chicago, Illinois. Gooderham, medical director at the SKiN Centre for Dermatology in Peterborough, Ontario, Canada, spoke on the idea of the modification of T regulatory cells and increasing the activity and number of T regulatory cells to better target or enhance the regulatory immunobalance of the skin.

On the topic of OX40, Gooderham said, “You may think about it as remission or possibly disease modification, but with the OX40 and OX40 ligand and the T regulatory agents, there seems to be a duration of response. So, after the therapy is stopped, patients are maintainingclear skin for weeks to months afterward."³

In a clinical setting, Dermatology Times previously reported in June 2023 that Sanofi announced positive topline data of its phase 2b study STREAM-AD, of amlitelimab a potential first novel investigational anti-OX40-ligand monoclonal antibody for the treatment of moderate to severe AD in adults. Overall, the company reported that the study demonstrated improvements in key secondary points and continued improvements were observed through week 24 in primary and key secondary outcomes. Biomarker results were reported to support an effect on both type 2 and non-type 2 pathways. Amlitelimab was well-tolerated across all dose arms and no new safety concerns were reported.⁴

References

1. Sadrolashrafi K, Guo L, Kikuchi R, et al. An ox-tra'ordinarytale: The role of OX40 and OX40L in atopic dermatitis. Cells. 2024;13(7):587. Published 2024 Mar 28. doi:10.3390/cells13070587
2. Buchanan L. The cutaneous connection: Navigating systemic therapies in atopic dermatitis. Dermatology Times.July 1, 2024. Accessed July 9, 2024. https://www.dermatologytimes.com/view/navigating-systemic-therapies-in-atopic-dermatitis 
3. Bader K, Gooderham M. Exploring new pathways in atopic dermatitis. Dermatology Times. June 10, 2024. Accessed July 9, 2024. https://www.dermatologytimes.com/view/exploring-new-pathways-in-atopic-dermatitis 
4. Positive topline phase 2b data in atopic dermatitis supportamlitelimab as a potential first and best-in-class novel investigational anti-OX40-ligand monoclonal antibody. Sanofi. June 27, 2023. Accessed July 9, 2024. https://www.sanofi.com/en/media-room/press-releases/2023/2023-06-27-05-30-00-2694938