JNJ-4804 Phase 2b Data Show Higher Week-48 Remission in Refractory UC, Crohn Disease

Johnson & Johnson has announced phase 2b results for the investigational co-antibody JNJ-4804 in adults with moderately to severely active ulcerative colitis (UC) or Crohn disease (CD) who had inadequate response or intolerance to systemic therapies, including a heavily pretreated subgroup with failure of at least 2 systemic therapy classes.

Data from the DUET-CD and DUET-UC studies were presented at Digestive Disease Week (DDW) 2026 in Chicago, IL, and showed the fixed-dose combination outperformed golimumab and was numerically higher than guselkumab on several week-48 efficacy measures in the overall study populations, with larger relative differences described in the highly refractory subgroup.

"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," Bruce 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, said in a statement. "The results from DUET-CD are particularly promising because they show meaningful clinical and endoscopic improvements in patients who have exhausted existing options.”

The rationale for JNJ-4804 reflects persistent unmet need in refractory IBD, where patients may cycle through anti-TNF, anti-integrin, IL-12/23 or IL-23 inhibitors, Janus kinase inhibitors, and sphingosine-1-phosphate receptor modulators yet still fail to achieve durable symptom control and mucosal improvement.

Phase 2b DUET Findings in Ulcerative Colitis and Crohn Disease

DUET-CD and DUET-UC are randomized, double-blind, dose-ranging phase 2b trials comparing JNJ-4804 with placebo and active comparator arms including guselkumab and golimumab. The studies enrolled adults with moderately to severely active disease and prior inadequate response or intolerance to ≥ 1 conventional or advanced systemic therapy, with approximately half of participants described by the company as having failed 2 or more therapy classes. JNJ-4804 combines guselkumab, an interleukin-23 inhibitor, and golimumab, a tumor necrosis factor inhibitor, in a single subcutaneous injection.

In CD, the company reported co-primary week-48 endpoints of clinical remission and endoscopic response. In the overall population, the high-dose JNJ-4804 group achieved clinical remission in 50.8% of patients compared with 25.4% for golimumab and 42.5% for guselkumab; endoscopic response rates were 38.1%, 19.8%, and 33.9%, respectively.

Clinical remission was defined as Crohn’s Disease Activity Index score < 150, and endoscopic response as > 50% improvement from baseline in Simple Endoscopic Score for Crohn’s Disease or a score of ≤ 2 by central reading.

In UC, the primary endpoint was week-48 clinical remission. Reported remission rates in the overall population were 41.0% with JNJ-4804, 11.5% with golimumab, and 34.0% with guselkumab.

For the subgroup with inadequate response to ≥ 2 systemic therapy classes, Johnson & Johnson reported JNJ-4804 showed clinically meaningful improvements across multiple clinical and endoscopic endpoints in both diseases, including remission rates nearly double the highest comparator in CD and almost 60% higher than the closest comparator in UC.

"There is a major unmet need for patients who either don't respond or are no longer responding to current UC treatments," said Maria Abreu, MD, 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."

Safety Findings and Future Outlook

Safety findings in both DUET studies were generally consistent with the known profiles of the component monotherapies.

In DUET-CD, exposure-adjusted safety events with JNJ-4804 were overall similar to or lower than placebo or golimumab. Across groups, most SAEs were GI-related and serious infection rates were low. Safety in the subpopulations was comparable to that in the overall population.

In DUET-UC, safety events per 100 patient-years in the JNJ-4804 groups were overall similar to or lower than in other groups. Like DUET-CD, across groups, most SAEs were GI-related and serious infection rates were low, and JNJ-4804 safety in the subpopulations was similar to the overall population.

Johnson & Johnson described plans to initiate phase 3 DUET ENCORE-CD and DUET ENCORE-UC trials.

References

1. Johnson & Johnson. Johnson & Johnson investigational co-antibody therapy JNJ-4804 shows potential to raise the bar for clinical efficacy in treating refractory inflammatory bowel disease. PR Newswire. Published May 05, 2026. Accessed May 05, 2026. https://www.prnewswire.com/news-releases/johnson--johnson-investigational-co-antibody-therapy-jnj-4804-shows-potential-to-raise-the-bar-for-clinical-efficacy-in-treating-refractory-inflammatory-bowel-disease-302761831.html

2. Abreu MT, Sands BE, Vermeire S, et al. EFFICACY AND SAFETY OF THE FIRST CO-ANTIBODY THERAPY, JNJ-78934804, IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS REFRACTORY TO SYSTEMIC THERAPIES. Presented at Digestive Disease Week (DDW) 2026; Chicago, IL; May 2–5, 2026.

3. Sands BE, D’Haens G, Dotan I, et al. EFFICACY AND SAFETY OF THE FIRST CO-ANTIBODY THERAPY, JNJ-78934804, IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE CROHN’S DISEASE REFRACTORY TO SYSTEMIC THERAPIES. Presented at Digestive Disease Week (DDW) 2026; Chicago, IL; May 2–5, 2026.

4. ClinicalTrials.gov. A study of combination therapy with guselkumab and golimumab in participants with moderately to severely active Crohn’s disease (DUET-CD). NCT05242471. Accessed May 05, 2026. https://clinicaltrials.gov/study/NCT05242471