J&J investigational co-antibody therapy JNJ-4804 shows potential to raise the bar for clinical efficacy in treating refractory inflammatory bowel disease

Johnson & Johnson (J&J) announced phase 2b data from two studies evaluating JNJ-4804, an investigational co-antibody therapy targeting both interleukin-23 (IL-23) and tumour necrosis factor-alpha (TNF-a), in patients with moderately to severely active ulcerative colitis (UC) and Crohn’s disease (CD) that is refractory to systemic therapies. The late-breaking presentations from the DUET-UC and DUET-CD studies were among the 32 company-sponsored abstracts being presented at Digestive Disease Week (DDW) 2026.

In both studies at Week 48, JNJ-4804 showed meaningful improvements across multiple clinical and endoscopic measures for a subpopulation of patients who are considered highly refractory and have had inadequate response to two or more systemic therapy classes.

In the overall population, JNJ-4804a demonstrated higher clinical remissionb rates (50.8%) and endoscopic responsec rates (38.1%) versus golimumab (25.4% for clinical remission, 19.8% for endoscopic response) at Week 48. The JNJ-4804 rates were also numerically higher than the rates achieved with guselkumab (42.5% for clinical remission and 33.9% for endoscopic response).

In the highly refractory subpopulation of patients with CD who have had inadequate response to two or more systemic therapy classes, JNJ-4804 showed clinically meaningful improvements at Week 48 across multiple clinical and endoscopic endpoints compared to golimumab and guselkumab monotherapies, and placebo. Clinical remission rates for JNJ-4804 were nearly double the highest comparator and more than 60% higher in endoscopic response rate.

“Despite many treatment advances for Crohn’s disease over the past two decades, many patients do not achieve long-term disease control with the currently available options, even after trying multiple monotherapies with different classes,” said Bruce E. Sands, MD, MS, Dr. Burrill B. Crohn Professor of Medicine at the Icahn School of Medicine, and Chief, Division of the Dr. Henry D. Janowitz Division of Gastroenterology at Mount Sinai Health System and presenting author of the DUET-CD study. “The results from DUET-CD are particularly promising because they show meaningful clinical and endoscopic improvements in patients who have exhausted existing options.”

In the overall population, JNJ-4804a demonstrated superior clinical remissiond rates compared to golimumab, with 41.0% of JNJ-4804-treated patients achieving clinical remission at Week 48 versus golimumab (11.5%), and numerically higher rates than guselkumab (34.0%).

In the highly refractory subpopulation of patients with UC who have had inadequate response to two or more systemic therapy classes, JNJ-4804 showed clinically meaningful improvements at Week 48 across multiple clinical and endoscopic endpoints compared to golimumab and guselkumab monotherapies, and placebo, with the clinical remission rate for JNJ-4804 being almost 60% higher than the closest comparator.

“There is a major unmet need for patients who either don’t respond or are no longer responding to current UC treatments,” said Dr. Maria Abreu, executive director of the F. Widjaja Inflammatory Bowel Disease Institute at Cedars-Sinai in Los Angeles and presenting author of DUET-UC. “The ongoing symptoms patients face when their UC is uncontrolled can profoundly impact their lives. The improvements we saw in DUET-UC are very encouraging, offering a potential new approach for patients with few options for long-term disease control.”

In both studies, safety findings were generally consistent with the known profiles of the component monotherapies.

Inflammatory bowel disease, including UC and CD, affects millions of people worldwide. While advances in biologics and targeted therapies have improved outcomes for many patients, many individuals either no longer respond or lose response over time. It is common for patients to cycle through multiple therapies while experiencing diminishing efficacy, leading to persistent symptoms such as abdominal pain, urgency, and bleeding. Ongoing inflammation can lead to irreversible bowel damage, hospitalization, and surgeries.  These challenges highlight a critical need for new treatments that can deliver meaningful disease control for patients who have been refractory to treatment with monotherapies.

“Inflammatory bowel disease involves multiple inflammatory pathways, which may help explain why some patients don’t respond or lose response to existing monotherapies,” said Esi Lamousé Smith, M.D., Ph.D., vice president, gastroenterology disease area lead, immunology, Johnson & Johnson. “By targeting the orthogonal pathways of IL-23 and TNFa, JNJ-4804 yields a synergistic therapeutic approach. The results from the DUET studies highlight its potential to change the treatment landscape.”

Based on results from the phase 2b DUET studies, Johnson & Johnson will be initiating the phase 3 DUET ENCORE-CD trial in adults with moderately to severely active CD as well as the phase 3 DUET ENCORE-UC trial in adults with moderately to severely active UC.

With these data, in addition to results from the phase 3 FUZION study of Tremfya (guselkumab) in perianal fistulizing Crohn’s disease, Johnson & Johnson therapies account for three late-breaking abstracts featured at DDW.

The DUET-UC (ulcerative colitis) and DUET-CD (Crohn’s disease) studies are randomized, double-blind, dose-ranging phase 2b studies comparing JNJ-4804 with placebo and active comparators, including guselkumab and golimumab. Patients enrolled in both studies had moderately to severely active disease with inadequate response or intolerance to one or more systemic therapy classes, including biologics and targeted oral therapies. Approximately half of participants in each study had previously experienced inadequate response to two or more therapy classes, representing a highly treatment-experienced population. The phase 2b DUET clinical programme builds on earlier proof-of-concept findings from the phase 2a VEGA study and is intended to inform potential registrational trials.

The primary endpoint of DUET-UC was clinical remission at Week 48. Key secondary endpoints included corticosteroid-free clinical remission, endoscopic improvement, histologic remission and endoscopic improvement (HREI) at Week 48.

The co-primary endpoints of DUET-CD were clinical remission at Week 48 and endoscopic response at Week 48. Key endpoints included endoscopic remission, deep remission and corticosteroid-free clinical remission at Week 48.

JNJ-4804 is an investigational co-antibody therapy designed to target both interleukin-23 (IL-23) and tumour necrosis factor-alpha (TNF-a), two inflammatory pathways involved in chronic immune-mediated diseases. JNJ-4804 is a fixed-dose combination of two proven therapies, guselkumab and golimumab, in a single, subcutaneous (SC) injection. JNJ-4804 is being studied in the phase 2b DUET clinical programme in inflammatory bowel disease and the phase 2a AFFINITY study in active psoriatic arthritis (PsA).

Ulcerative colitis (UC) is a chronic disease of the large intestine, also known as the colon, in which the lining of the colon becomes inflamed and develops tiny open sores, or ulcers, that produce pus and mucus. It is the result of the immune system’s overactive response. Symptoms vary but may typically include loose and more urgent bowel movements, rectal bleeding or bloody stool, persistent diarrhoea, abdominal pain, loss of appetite, weight loss, and fatigue. Currently there is no cure available for UC. 

Crohn’s disease is one of the two main forms of inflammatory bowel disease, which affects an estimated three million Americans and an estimated four million people across Europe. Crohn’s disease is a chronic inflammatory condition of the gastrointestinal tract with no known cause, but the disease is associated with abnormalities of the immune system that could be triggered by a genetic predisposition, diet, or other environmental factors. Symptoms of Crohn’s disease can vary, but often include abdominal pain and tenderness, frequent diarrhoea, rectal bleeding, weight loss, and fever. Currently no cure is available for Crohn’s disease.

Developed by Johnson & Johnson, Tremfya is the first fully-human, dual-acting monoclonal antibody designed to neutralize inflammation at the cellular source by blocking IL-23 and binding to CD64 (a receptor on cells that produce IL-23). Findings for the dual-acting mechanism are limited to in vitro studies that demonstrate guselkumab binds to CD64, which is expressed on the surface of IL-23 producing cells in an inflammatory monocyte model. The clinical significance of this finding is not known.

Tremfya is a prescription medicine approved in the US to treat:

• adults and children 6 years and older who also weigh at least 88 pounds (40 kg) with moderate to severe plaque psoriasis who may?benefit?from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet or UV light).?
• adults and children 6 years and older who also weigh at least 88 pounds (40 kg) with active psoriatic arthritis.?
• adults with moderately to severely active ulcerative colitis.?
• adults with moderately to severely active Crohn’s disease. ? ?