IL-23, a cytokine secreted by activated monocyte/macrophage and dendritic cells, is known to be a driver of inflammatory diseases, including plaque psoriasis (PsO), psoriatic arthritis (PsA), and inflammatory bowel disease (IBD).3,a CD64 is a receptor that binds the Fc region of immunoglobulin G4 and is highly expressed on the surface of certain immune cells that are major producers of IL-23.4-7
'The initial results of these studies show the potential differentiating mechanism of TREMFYA,' said presenting study author
The MODIF-Y studies explored mechanisms potentially underpinning therapeutic profile differences between TREMFYA, a fully human monoclonal antibody specific for the p19 subunit of IL-23 with a native Fc region, and risankizumab, a humanized anti-IL-23 monoclonal antibody with a mutated Fc region.
Differentiated, Local Neutralization of IL-23 at its Source
The results from these studies show that TREMFYA is differentiated from risankizumab by the capacity of TREMFYA to bind via its native Fc region to CD64, which is expressed on IL-23-producing cells.1This raises the possibility that TREMFYA may bind to IL-23 while also being localized to IL-23-producing cells through its binding to CD64, thus neutralizing IL-23 at its cellular source.1Risankizumab shows negligible binding to CD64 due to its mutated Fc region.1,8
CD64+ mononuclear phagocytes represent the predominant IL-23 source in psoriatic skin and IBD, and increased frequency of CD64+ monocytes correlates with markers of joint disease activity in active PsA.5-7
These studies also showed that TREMFYA and risankizumab display comparable affinity for binding IL-23 and potency for inhibiting IL-23-mediated signaling.1
Potential for Enrichment in Inflamed Tissues
Binding to CD64 raises the hypothesis that the presence of TREMFYA may be enriched at the intercellular interface between IL-23-producing and -responsive cells within the inflamed tissue. This may in turn enhance the ability of TREMFYA to neutralize IL-23 where it is produced in inflammatory diseases.1
The results of these molecular investigations follow previous publications of Phase 3 clinical trials demonstrating the durable, long-term efficacy and safety profile of TREMFYA based on five years of data in plaque PsO and two years of data in PsA.9-11
'This ability of TREMFYA to capture IL-23 right where it is produced, preventing permanent activation of IL-23-responsive cells, may help explain its durable clinical efficacy in psoriatic disease,' said
Further in vivo research is being conducted on the biodistribution of TREMFYA and its correlation to efficacy in the treatment of patients with PsA (NCT05083078) and IBD, which includes ongoing Phase 3 trials in Crohn's disease (NCT03466411) and ulcerative colitis (NCT04033445).12-14 Janssen is dedicated to continuing to investigate the pathways underlying immune-mediated diseases, focusing on improving the regulation of the immune system to create novel treatments that can effectively address the root cause of disease.
About the MODIF-Y Program1
The in vitro MODIF-Y studies were designed to explore potential mechanisms underpinning differences in therapeutic profiles between TREMFYA (guselkumab), a fully human monoclonal immunoglobulin G1 lambda (IgG1?) antibody specific for IL-23p19 with a native Fc region, and risankizumab, a humanized anti-IL-23 IgG1 with a mutated Fc region, in inflammatory diseases. Functional characteristics of the antigen-binding and Fc regions of the two antibodies were compared.
About Plaque Psoriasis (PsO)
Plaque PsO is an immune-mediated disease resulting in an overproduction of skin cells, which causes inflamed, scaly plaques that may be itchy or painful.15 It is estimated that eight million Americans and more than 125 million people worldwide live with the disease.16 Nearly one-quarter of all people with plaque PsO have cases that are considered moderate to severe.16 Living with plaque PsO can be a challenge and impact life beyond a person's physical health, including emotional health, relationships, and handling the stressors of life.17
About Psoriatic Arthritis (PsA)
PsA is a chronic, immune-mediated inflammatory disease characterized by peripheral joint inflammation, enthesitis (pain where the bone, tendon and ligament meet), dactylitis (severe inflammation of the fingers and toes), axial disease, and the skin lesions associated with plaque PsO.18-20 In addition, in patients with PsA, comorbidities such as obesity, cardiovascular diseases, anxiety and depression are often present.21 Studies show up to 30 percent of people with plaque PsO also develop PsA.22 The disease causes pain, stiffness and swelling in and around the joints; it commonly appears between the ages of 30 and 50, but can develop at any age.22 Nearly half of patients with PsA experience moderate fatigue and about 30 percent suffer from severe fatigue as measured by the modified fatigue severity scale.23 Although the exact cause of PsA is unknown, genes, the immune system and environmental factors are all believed to play a role in disease onset.24
About TREMFYA (guselkumab)25
Developed by Janssen, TREMFYA is the first approved fully human monoclonal antibody that selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor. IL-23 is an important driver of the pathogenesis of inflammatory diseases such as moderate to severe plaque PsO and active PsA. TREMFYA is approved in the
About the Janssen Pharmaceutical Companies of
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Cautions Concerning Forward-Looking Statements
This press release contains 'forward-looking statements' as defined in the Private Securities Litigation Reform Act of 1995 regarding TREMFYA (guselkumab) product development. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of
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