Further findings from in vitro MODIF-Y tests from the Janssen Pharmaceutical Companies of Johnson & Johnson reinforce the idea that not all IL-23 inhibitors work the same way by showing that Tremfya (guselkumab) and risankizumab have different binding mechanisms. According to research, guselkumab can attach to CD64+a myeloid cells, which are the main cause of IL-23-induced inflammation in the gut, in a dose-dependent manner. This is one of the 22 oral and poster presentations that Janssen will be making at the 18th Congress of the European Crohn’s and Colitis Organization (ECCO), which will be held March 1–4 in Copenhagen, Denmark.
“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 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. c “Importantly, these data demonstrate that guselkumab has the distinct ability to bind to critical inflammatory cells, neutralising IL-23 where it is generated in the local tissue milieu, suggesting mechanistic benefit,” the authors write.
The ability of guselkumab for dual binding enables simultaneous binding to CD64 and neutralisation of IL23 at its cellular source, differentiating guselkumab within the IL-23p19 inhibitor class, according to the findings of a study comparing functional binding characteristics of guselkumab and IL-23 inhibitor risankizumab; Comparatively, risankizumab demonstrated minimal binding to transfected cell lines expressing Fc? receptors (Fc?Rs), such as CD64; both treatments shown comparable binding affinities for IL-23 and equivalent potency in the suppression of IL-23.
The results of our study show Janssen’s dedication to fundamental molecular science and reaffirm our dedication to creating treatments that could help meet unmet patient needs, according to Dan Cua, Ph.D., vice president and IL-23 Distinguished Fellow in Immunology at Janssen Research & Development, LLC. In order to provide healthcare professionals with a variety of treatment options, we continue to research the underlying science of guselkumab to better understand its mechanistic differences from other IL-23 inhibitors as well as the expanding complexity of immune-mediated diseases like inflammatory bowel disease.
Guselkumab is the subject of ongoing phase 3 trials for Crohn’s disease (NCT03466411) and ulcerative colitis, two inflammatory bowel diseases that are being studied as part of guselkumab research to determine how to treat these individuals (NCT04033445). Adults with UC or CD are not eligible for treatment with Tremfya (guselkumab) in the US. The Fc region of antibodies can be bound by the CD64+ receptor, which is expressed on immune cells that are important sources of IL-23. Inflammatory bowel illness causes an increase in CD64+ IL-23-producing myeloid cells, and the frequency of these cells is associated with the severity of the disease on endoscopy. Janssen provided Dr. Atreya with a grant. He hasn’t received any payment for his work in the media. For both guselkumab and risankizumab, IL-23 binding affinity and cellular potency were comparable.
The in vitro MODIF-Y studies were created to investigate possible mechanisms underlying potential therapeutic profile differences between Tremfya (guselkumab), a fully human monoclonal immunoglobulin G1 lambda (IgG1?) antibody specific for IL-23p19 with a native Fc region, and risankizumab, a humanised anti-IL-23p19 IgG1? with a mutated Fc region. We compared the functional properties of the two antibodies’ Fc and antigen-binding domains.
Crohn’s disease and ulcerative colitis are two illnesses that cause chronic inflammation of the gastrointestinal (GI) tract and are together referred to as “inflammatory bowel disease” (IBD). The GI tract is harmed by persistent inflammation. IBD has an unclear specific aetiology, however it could be brought on by the immune system’s reaction to environmental factors or a hereditary predisposition. Constant diarrhoea, stomach pain, rectal bleeding, bloody stools, exhaustion, and weight loss are just a few of the symptoms that might occur.
Tremfya, created by Janssen, is the first entirely human monoclonal antibody that has been given official approval. It targets the p19 subunit of interleukin (IL)-23 and prevents it from interacting with the IL-23 receptor. Inflammatory illnesses such active psoriatic arthritis and moderate to severe plaque psoriasis (PsO) are largely driven by the cytokine IL-23 (PsA). For the treatment of adult patients with active PsA and moderate to severe plaque PsO who are candidates for injections, tablets, phototherapy, or other forms of systemic therapy, Tremfya has received approval in the US, Canada, Japan, and a number of other nations. Additionally, it is approved for use in the EU to treat moderate to severe plaque PsO in adults who are suitable candidates for systemic therapy as well as to treat active PsA in adults who have received insufficient benefit from or were intolerant to a prior disease-modifying antirheumatic drug therapy.
