Janssen’s Tremfya, an IL-23 inhibitor, is showing an ability to separate itself from AbbVie’s Skyrizi in preventing the activation of cells that drive inflammation.
New data shows the difference between Tremfya and Skyrizi’s mechanism. (Shutterstock/Michael Vi)
Janssen’s Tremfya, an IL-23 inhibitor, is showing an ability to separate itself from AbbVie’s Skyrizi in preventing the activation of cells that drive inflammation.
On Wednesday, Janssen presented data from the in vitro MODIF-Y studies that support a hypothesis that highlights the differentiated mechanism of action of Tremfya (guselkumab) from Skyrizi (risankizumab). That difference hinges on Tremfya’s ability to bind to CD64 positive (CD64) cells in addition to interleukin (IL)-23 - both of which are key components of the immune system. In its presentation at the Society for Investigative Dermatology annual meeting, Janssen suggested the information suggests that Tremfya has the potential to neutralize IL-23 at the site where it is secreted. The hypothesis will continue to be evaluated in both in vitro and in vivo studies, the company said.
James G. Krueger, the lead author of the presentation and the co-director of the Center for Clinical and Translational Science, The Rockefeller University in New York, said the initial results from the MODIF-Y study highlight the potential differentiating mechanism of Tremfya from Skryrizi.
“Its ability to bind to CD64+ cells may physically place Tremfya 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 Tremfya to neutralize IL-23 where it is being produced and prevent IL-23 from acting in the local tissue microenvironment,” Krueger said in a statement.
IL-23 is a known driver of multiple inflammatory diseases, including plaque psoriasis, psoriatic arthritis and inflammatory bowel disease. CD64 is a receptor that binds the Fc region of immunoglobulin G4. CD64 is highly expressed on the surface of certain immune cells that are major producers of IL-23.
The MODIF-Y studies explored mechanisms that could potentially highlight the therapeutic profile differences between Tremfya and Skyrizi, a humanized anti-IL-23 monoclonal antibody with a mutated Fc region. Janssen’s data showed the differences between the mechanisms of action due to Tremfya’s ability to bind to CD64 through its native Fc region. The company said this suggests that Tremfya may potentially neutralize the production of IL-23. Janssen said Skyrizi “shows negligible binding to CD64 due to its mutated Fc region.”
Dan Cua, vice president and IL-23 pathway leader at Janssen, said this discovery of Tremfya’s ability to capture IL-23 where it is produced may halt permanent activation of IL-23-responsive cells and can also explain the drug’s durable clinical efficacy in psoriatic disease.
“These molecular studies also inform current and future research that fuel our critical understanding of IL-23 pathway mechanisms, biodistribution patterns, and clinical outcomes, as we seek to provide patients with more efficacious and lasting treatments across a number of inflammatory diseases,” Cua said in a statement.
In the U.S. Tremfya has been approved for the treatment of adult patients with moderate to severe plaque psoriasis who may benefit from systemic therapy or phototherapy. The U.S. Food and Drug Administration has also greenlit Tremfya as a treatment for active psoriatic arthritis, the first time an IL-23 inhibitor was approved as a treatment for the chronic progressive disease.
