TREMFYA (guselkumab) Demonstrates a Differentiated Binding Mechanism from Risankizumab in In Vitro Studies

Janssen Pharmaceutical

SPRING HOUSE, PA The Janssen Pharmaceutical Companies of Johnson & Johnson recently announced additional results from in vitro MODIF-Y studies, which continue to support a hypothesis that not all IL-23 inhibitors are the same by demonstrating a differentiated binding mechanism for TREMFYA® (guselkumab) from risankizumab. Findings show that guselkumab is able to dose-dependently bind to CD64+a myeloid cells,1 the predominant source of IL-23-driven inflammation in the gut.2,b Data comprise one of Janssen’s 22 oral and poster presentations at the 18th Congress of the European Crohn’s and Colitis Organization (ECCO), taking place in Copenhagen, DenmarkMarch 1-4.

“These data provide new insights into the mechanism of action of guselkumab and can help in the development of treatments for conditions like inflammatory bowel disease” said study author Raja Atreya, M.D., Senior Physician and Head of the Inflammatory Bowel Disease Unit, Outpatient Clinic, and Clinical Study Centre at the Erlangen University Hospital, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.“Importantly, these data show that guselkumab has the unique ability to bind to key cells involved in inflammation, neutralizing IL-23 where it is being produced in the local tissue microenvironment, suggesting mechanistic benefit.”

MODIF-Y in vitro outcomes (Poster P504):1

Results from a study comparing functional binding characteristics of guselkumab and IL-23 inhibitor risankizumab show:

  • The capacity of guselkumab for dual binding enables simultaneous binding to CD64 and neutralization of IL23 at its cellular source, differentiating guselkumab within the IL-23p19 inhibitor class
  • Comparatively, risankizumab showed negligible binding to transfected cell lines expressing Fcγ receptors (FcγRs) including CD64
  • Both therapies displayed comparable binding affinityfor IL-23 and equivalent potency in the inhibition of IL-23
READ:  STRATA Skin Sciences Affirms No Exposure to Silicon Valley Bank

“The findings from our study demonstrate Janssen’s commitment to foundational molecular science and reinforce our commitment to developing therapies that may help address unmet patient need,” said Dan Cua, Ph.D., Vice President, IL-23 Distinguished Fellow, Immunology, Janssen Research & Development, LLC. “We continue to investigate the underlying science of guselkumab to further understand mechanistic differences from other IL-23 inhibitors, as well as the growing immune-mediated disease complexities such as inflammatory bowel disease, so that healthcare professionals have an array of treatment options to consider.”

Further research is currently being conducted on guselkumab to investigate treatment of patients with inflammatory bowel disease, which includes ongoing Phase 3 trials in Crohn’s disease (NCT03466411) and ulcerative colitis (NCT04033445).3,4

TREMFYA (guselkumab) is not approved for the treatment of adults living with UC or CD in the U.S.


a. CD64+ is a receptor that binds to the Fc region of antibodies and is expressed on immune cells that are major producers of IL-23.2

b. Frequencies of CD64+ IL-23–producing myeloid cells are increased in the inflamed colon in inflammatory bowel disease and correlated with endoscopic disease severity.2,5

c. Dr. Atreya received grant support from Janssen. He has not been compensated for any media work.

d. IL-23 binding affinity and cellular potency were similar for guselkumab and risankizumab.1


  1. Atreya, R, et al. Guselkumab, An IL-23p19 Subunit–specific Monoclonal Antibody, Binds CD64+ Myeloid Cells and Potently Neutralizes IL-23 Produced from the Same Cells. Presented at the 18th Congress of ECCO, March 1-4.
  2. Chapuy, L. et al. Two distinct colonic CD14+ subsets characterized by single-cell RNA profiling in Crohn’s disease. Mucosal immunology: 2019; vol 12,3; 703-719. Available at: Accessed February 2023.
  3. National Institutes of Health: A Study of the Efficacy and Safety of Guselkumab in Participants With Moderately to Severely Active Crohn’s Disease (GALAXI). Identifier: NCT03466411. Available at: Accessed February 2023.
  4. National Institutes of Health: A Study of Guselkumab in Participants With Moderately to Severely Active Ulcerative Colitis (QUASAR). Identifier: NCT04033445. Available at: Accessed February 2023.
  5. Chapuy, L. et al. IL-12 and Mucosal CD14+ Monocyte-Like Cells Induce IL-8 in Colonic Memory CD4+ T Cells of Patients With Ulcerative Colitis but not Crohn’s Disease. Journal of Crohn’s and Colitis. 2020; 14: 79-95. Accessed February 2023.
  6. Krueger, J. et al. Differentiation of therapeutic antibodies targeting IL-23. Presented at the Society for Investigative Dermatology (SID) 2022 Annual Meeting, May 18-21, 2022.
  7. Centers for Disease Control and Prevention. What is IBD? Available at: Accessed February 2023.
  8. TREMFYA® Prescribing Information. Available at: Accessed February 2023.
READ:  Safety Improvements Continue on U.S. 13 in Montgomery County

For the latest news on everything happening in Chester County and the surrounding area, be sure to follow MyChesCo on Google News.

Thanks for visiting! Looking for some Chester County pride? We got you covered! Shop our MyChesCo store and show your love for Chester County, Pennsylvania. We got shirts, hats, and more – all with a unique ChesCo flair. Plus, proceeds from each purchase helps support our mission of bringing reliable information and resources to the people of Chester County.