Janssen Unveils New Mechanistic Data on IL-23 Inhibitor Tremfya Demonstrating Sustained Target Engagement in Multiple Inflammatory Diseases

Compiled by Draven

Recently, Janssen Pharmaceuticals announced the in vitro MODIF-Y study data of the anti-inflammatory drug Tremfya, validating a new molecular mechanism of action.

MODIF-Y Study: Janssen's Exploration Based on the Differences in Mechanism of Action Between Tremfya and AbbVie’s SkyriziSpecifically, the MODIF-Y data demonstrates Tremfya's ability to bind with IL-23 and CD64-positive (CD64+) cells — both of which are key components of the immune system. The binding of Tremfya to CD64+ cells anchors Tremfya to the surface of these IL-23-producing immune cells, enabling Tremfya to exert its inhibitory effects at the site of IL-23 production and prevent IL-23 from acting within the local tissue microenvironment.

Janssen's data shows that Tremfya can bind to CD64 through its natural Fc region, thereby inhibiting the expression of IL-23. Skyrizi, on the other hand, is a humanized anti-IL-23 monoclonal antibody with a mutated Fc region, and due to this Fc mutation, its binding to CD64 is negligible.

IL-23 is a naturally occurring cytokine and a known driver of multiple inflammatory diseases, including plaque psoriasis, psoriatic arthritis, and inflammatory bowel disease. CD64 is a receptor that binds to the Fc region of immunoglobulin G4, and CD64 is highly expressed on the surface of certain immune cells, which are the main producers of IL-23.

Tremfya (guselkumab) is the first regulatory-approved selective IL-23 inhibitor. Tremfya is a monoclonal antibody that selectively binds to the p19 subunit of IL-23, inhibiting the interaction of IL-23 with its receptor and simultaneously suppressing the release of pro-inflammatory cytokines and inflammatory chemokines.

Tremfya was approved by the FDA in July 2017 for the treatment of moderate to severe plaque psoriasis; in February 2019, the FDA approved the self-injection version for the treatment of adult plaque psoriasis; in November 2018, it was approved for marketing in Hong Kong; in December 2019, it was approved for marketing in China. To date, Tremfya has been approved in more than seventy countries worldwide for the treatment of adult patients with moderate to severe plaque psoriasis.

Dan Cua, Vice President of Janssen and Head of the IL-23 Pathway, stated that these molecular studies provide insights for current and future research, driving a critical understanding of the mechanisms, biodistribution patterns, and clinical outcomes of the IL-23 pathway, while also helping to deliver more effective and durable treatments for patients with various inflammatory diseases.

Reference Source:

Janssen Presents New Data that could Set Anti-Inflammatory Drug Apart