Collaborating to Address Moderate to Severe Atopic Dermatitis

Atopic dermatitis, the most common form of eczema, is a common, chronic condition characterized by skin redness, itching and pain. Often beginning in childhood, atopic dermatitis affects 15–20% of children and up to 10% of adults, making it the 15th most common nonfatal disease.¹ Atopic dermatitis is prevalent in countries globally, with approximately 1 in 3 people with atopic dermatitis worldwide classifying their disease as moderate to severe.^2-7

The exact cause of this disease is complex and many people’s symptoms still remain inadequately controlled, despite currently available treatment options.^5,6 However, there is research underway for a potential new approach to treating moderate to severe atopic dermatitis.

More Than Just a Rash

Atopic dermatitis occurs when immune system cells cause skin inflammation leading to chronic symptoms made worse by periodic, unpredictable flare-ups that can be painful and disruptive to everyday life.⁶ Those with moderate to severe atopic dermatitis report unbearable itching, leading to repeated scratching which can cause the skin to thicken, harden and become vulnerable to infections.^7,8

Due to its chronic nature and direct and indirect impact on multiple aspects of the lives of patients and their families, atopic dermatitis has the highest burden of disease among all nonfatal skin disorders.⁹

T Cells and the Vicious Cycle of Atopic Dermatitis

T cells are white blood cells that play an essential role in the immune system. However, in people with atopic dermatitis, T cells play a major role in the disease, triggering an overactive immune response that causes blood vessels to dilate, leak and attract even more immune cells to the area.¹⁰ The result is lesions on the surface of the skin, making it dry, itchy and much more prone to damage and infection.¹⁰

Targeting OX40 for Moderate to Severe Atopic Dermatitis

This inflammatory cycle initiated and perpetuated by T cells is one of the reasons moderate to severe atopic dermatitis can be so challenging to treat. However, new research has shown that targeting and inhibiting a particular receptor expressed on pathogenic T cells, called OX40, may help impact this cycle.¹¹

That’s why Amgen, in collaboration with Kyowa Kirin, is pursuing research of rocatinlimab (AMG 451/KHK4083), a potential first-in-class, anti-OX40 monoclonal antibody being investigated for people with moderate to severe atopic dermatitis.

OX40, a co-stimulatory molecule predominantly expressed on activated effector T cells, is prominently expressed in people with atopic dermatitis.¹²

Rocatinlimab inhibits and reduces the number of OX40 pathogenic T cells responsible for driving systemic and local atopic dermatitis inflammatory responses.¹³ Through its mechanism of action, rocatinlimab is designed to block OX40 and prevent the generation of signals that are critical for the expansion and survival of pathogenic T cells and the subsequent generation of memory T cells, thereby inhibiting the inflammatory response.¹³

The latest findings from Phase 2b of the ongoing clinical study, recently published in The Lancet, support the continued evaluation of rocatinlimab for the treatment of moderate to severe atopic dermatitis in Phase 3 studies.

Working Together to Investigate a Potential Therapy for Moderate to Severe Atopic Dermatitis

Amgen and Kyowa Kirin recently began recruiting participants for a comprehensive, global Phase 3 program (ROCKET program) to investigate the safety and efficacy of rocatinlimab in a heterogeneous moderate to severe atopic dermatitis population suffering from a high burden of disease.¹⁴ The ROCKET Phase 3 program, made up of seven global studies, will investigate the following populations:

• Patients from diverse demographics across different ethnicities, geographies and age ranges, including adolescents and adults suffering from moderate to severe atopic dermatitis
• Patients naïve to biologics or Janus kinase inhibitors
• Patients who received a prior biologic or Janus kinase inhibitor

"We want to downregulate OX40 because it’s highly elevated in lesional and even non-lesional skin of people with atopic dermatitis. This is an exciting potential new class of therapy, because in addition to targeting the disease, you are targeting the disease activity,” said Emma Guttman, MD, PhD, Professor, Dermatologist, Health System Chair, Department of Dermatology at Icahn School of Medicine at Mount Sinai. “The ROCKET program offers people a unique opportunity to participate in a potentially disease-modifying study.”

To learn more about the Phase 3 ROCKET program, please visit ClinicalTrials.gov.

Resources

• Global Parents for Eczema Research
• National Eczema Association
• International Alliance of Dermatology Patient Organizations (GlobalSkin)
• International Eczema Council

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References

1. Ständer, M.D. Atopic Dermatitis. The New England Journal of Medicine. 2021.
2. Hou A, et al. Arch Dermatol Res. 2021. doi:10.1007/s00403-021-02219-w.
3. Silverberg JI, et al. J Allergy Clin Immunol Pract. 2019;7:1524-1532.e2.
4. Silverberg JI, et al. Ann Allergy Asthma Immunol. 2021;126:417-428.
5. Barbarot S, et al. Allergy. 2018;73:1284-1293.
6. Asher MI, et al. Lancet. 2006;368:733-743.
7. Wang X, et al. Medicine (Baltimore). 2017;96:e6317
8. Eichenfield LF, Tom WL, Chamlin SL, et al. Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2014;70(2):338-351.
9. Avena-Woods C. Overview of atopic dermatitis. Am J Manag Care. 2017;23(8 Suppl):S115-S123.
10. J Invest Dermatol. 2019 Mar;139(3):583-590. doi: 10.1016/j.jid.2018.08.028. Epub 2018 Oct 30.
11. Frankel HC et al., Am J Clin Dermatol 2012
12. Aad.org. 2022. Eczema types: Atopic dermatitis overview. [online] Available at: [Accessed 6 June 2022].
13. Langan SM, Irvine AD, Weidinger S. Atopic dermatitis. The Lancet. 2020;396(10247):345-360. doi:10.1016/s0140-6736(20)31286-1
14. Eichenfield L et al., J AM Acad Dermatol 2013