Unleashing the Potential of OX40: The Next Challenger to Dupilumab

In recent developments, Sanofi has registered a Phase 2 open-label, long-term study on the Chinese Clinical Trial Registry platform to evaluate the safety and efficacy of a potential "first-in-class" OX40 signal pathway inhibitor called amlitelimab in adult patients with moderate to severe atopic dermatitis. With the advantage of potential dosing every 12 weeks, amlitelimab shows promise in challenging the position of dupilumab in the treatment of atopic dermatitis.

The OX40 Target: Antagonists in AD and Agonists in Cancer Treatment:

OX40, also known as CD134, ACT35, and TNFRSF4, was first discovered in activated mouse CD4+ T cells in 1987 and belongs to the TNFR superfamily. OX40 is an important T cell activation stimulator, and both activating and inhibiting OX40/OX40L signals can produce therapeutic effects. In atopic dermatitis and other inflammatory diseases, OX40L activates the OX40 signaling pathway, promoting the activation of Th2 helper T cells and leading to inflammation. Therefore, OX40 and OX40L have emerged as potential targets for the treatment of atopic dermatitis. On the other hand, using OX40 agonist antibodies enhances T cell-mediated anti-tumor immunity, aiding tumor regression and prolonging survival. However, the therapeutic potential of OX40 agonist antibodies in the field of cancer treatment is still in the conceptual validation stage.

Competition in the OX40 Landscape:

OX40 has become a hot target in the field of new drug development. Globally, several OX40 antibodies have entered clinical trials, including rocatinlimab by Amgen and amlitelimab by Sanofi, both in Phase 3 trials. In China, OX40 antagonists developed by Hengrui Medicine/Chuangxiang Biology, Bio-Thera, and Xinda Biotechnology are in Phase 1 clinical trials.

Rocatinlimab (KHK4083):

Rocatinlimab is an anti-OX40 monoclonal antibody that inhibits and reduces the number of activated T cells expressing OX40. In June 2021, Amgen acquired the rights for development, production, and commercialization outside of Japan by paying $400 million as an upfront payment and $850 million in milestone payments. The Phase 3 clinical trial of Rocatinlimab, named ROCKET-ASCEND, was initiated in China in October 2023 to evaluate its long-term safety, tolerability, and efficacy in adult and adolescent patients with moderate to severe atopic dermatitis. Previous Phase 2 clinical trial results demonstrated significant improvements in eczema area and severity index (EASI) scores after 16 weeks of treatment with Rocatinlimab compared to placebo.

Amlitelimab:

Initially developed by Kymab, amlitelimab is an anti-OX40 antibody that has shown promising safety and efficacy data in the treatment of moderate to severe atopic dermatitis, along with rocatinlimab. Amlitelimab's Phase 2 clinical trials demonstrated statistically significant improvements in EASI scores compared to placebo across different dosing regimens.

The emergence of OX40 inhibitors and agonists represents an exciting development in the treatment of atopic dermatitis and cancer. Sanofi's amlitelimab holds the potential to challenge the position of dupilumab in atopic dermatitis treatment, offering the advantage of less frequent dosing. With ongoing clinical trials and increasing competition in the OX40 landscape, further breakthroughs are expected in the field of immunotherapy for various diseases, bringing new hope to patients in need.