Johnson & Johnson plans to advance the co-antibody therapy, which combines its IL-23 blocker Tremfya and the TNF-alpha inhibitor Simponi, into late-stage testing for Crohn’s disease and ulcerative colitis.
Johnson & Johnson’s investigational antibody combo failed to significantly improve remission and response in a pair of mid-stage trials of inflammatory bowel diseases, but that isn’t stopping the pharma from forging ahead to pivotal testing.
The investigational co-antibody therapy, dubbed JNJ-4804, is a fixed-dose combination of the pharma’s anti-IL-23 therapy Tremfya and TNF-alpha blocker Simponi. Combining both molecules in one therapy “yields a synergistic therapeutic approach” for patients resistant to monotherapies, Esi Lamousé Smith, vice president of J&J’s Gastroenterology Disease Area, said in a Tuesday release.
Data presented Tuesday at Digestive Disease Week 2026 in Chicago, however, haven’t borne that out. In the Phase 2b DUET-CD study, high-dose JNJ-4804 showed significantly higher clinical remission and endoscopic response rates versus monotherapy with Simponi, but not versus Tremfya. This study focused on patients with moderate to severe Crohn’s disease with poor responses or intolerance to at least one prior line of systemic therapy.
The mid-stage DUET-UC study, which focused on ulcerative colitis, reached similar outcomes—JNJ-4804 elicited significantly greater clinical remission than Simponi but not Tremfya. Endoscopic improvement, which in this study was set as a secondary endpoint, was “numerically higher” in those treated with the combo therapy versus Tremfya or Simponi alone.
In a news release shared alongside these abstracts, however, J&J homed in on patients “who are considered highly refractory”—those who have shown suboptimal response to at least two classes of systemic therapies. In these populations, according to the pharma, JNJ-4804 elicited “meaningful improvements across multiple clinical and endoscopic measures.”
These signals warrant further development, according to J&J, which on Tuesday said it would launch the Phase 3 DUET ENCORE-CD study in Crohn’s disease and DUET ENCORE-UC study in ulcerative colitis.
“Although the DUET studies missed the primary endpoint, we do believe the positive trends support the idea that combination approaches are needed to raise the efficacy bar in IBD,” William Blair analysts wrote to investors on Tuesday.
“However, with the signal being driven by the most refractory patients, we believe it also highlights the importance of targeting the right subpopulation,” they added. J&J hasn’t yet specified its target population for the DUET ENCORE programs, nor has it said when the studies are set to start.
