New Data Show J&J Unit’s Tremfya Binds to Both Inflammatory Cells, Interleukin (IL)-23


The study results support a hypothesis for a differentiated mechanism from risankizumab, the company says.

Janssen Pharmaceutical Companies of Johnson & Johnson announced the first results of the in vitro MODIF-Y studies, which supported a hypothesis that may differentiate the mechanism of first-on-class guselkumab (Tremfya) from risankizumab, according to a statement from the company.

Investigators said they can differentiate the 2 drugs, because of the ability of guselkumab binding to CD64 positive cells in addition to interleukin-23 (IL-23), which are both key components of the immune system.

“The initial results of these studies show the potential differentiating mechanism of guselkumab,” James Krueger, MD, PhD, D Martin Carter professor in clinical investigation and co-director of the Center for Clinical and Translational Science at The Rockefeller University in New York, said in the statement.

“Its ability to bind to CD64+ cells may physically place guselkumab right on the surface of these major IL-23-producing immune cells, which are key drivers of inflammation in diseases such as psoriasis and psoriatic arthritis. This potentially allows guselkumab to neutralize IL-23 where it is being produced and prevent IL-23 from acting in the local tissue microenvironment,” Krueger said.

The results, which will be presented at the Society for Investigative Dermatology annual meeting, showed that guselkumab binds simultaneously to CD64 via its native fragment crystallizable region and to IL-23 via its antigen-binding region, suggesting the potential to neutralize IL-23 at the side where it is secreted. Risankizumab shows negligible binding to CD64 because of the mutated Fc region.

Additionally, CD64+ mononuclear phagocytes represent the predominant IL-23 source in psoriatic skin and inflammatory bowel disease (IBD). Increased frequency of CD64+ monocytes correlate with markers of joint disease in active psoriatic arthritis (PsA).

The results of these investigations follow previous publication of phase 3 trials that show the durable, long-term efficacy and safety profile of guselkumab based on 2 years of data in PsA and 5 years of data in plaque plaque psoriasis (PsO).

Further studies will be conducted in vitro and in vivo to generate additional evidence supporting the hypothesis. Additional studies will also be conducted on the biodistribution of guselkumab and its correlation to efficacy in the treatment of individuals with PsA and IBD, including phase 3 trials in Crohn disease and ulcerative colitis.

Furthermore, binding to CD64 raises the hypothesis that the presence of guselkumab may be enriched at the intercellular interface between IL-23-producing and -responsive cells within the inflamed tissue.

Investigators think that this could enhance the ability of guselkumab to neutralize IL-23 where it is produced in inflammatory diseases.

IL-23, a cytokine secreted by activated monocyte/macrophage and dendritic cells, is a known driver of inflammatory diseases, including IBD, PsA, and PsO. CD64 is a receptor that binds to the Fc region of immunoglobulin G4 and is expressed on the surface of immune cells that are producers of IL-23.

Guselkumab (Tremfya) is a fully human monoclonal antibody specific for the p19 subunit of IL-23 with a native Fc region, while Risankizumab is a humanized anti-IL-23 monoclonal antibody with a mutated Fc region.


New data show Tremfya (guselkumab) binds to both inflammatory cells and interleukin (IL)-23, supporting a hypothesis for a differentiated mechanism from risankizumab. Johnson & Johnson. News release. May 18, 2022. Accessed May 19, 2022.

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