AbbVie’s investigational dual-targeting therapy ABBV-466 has demonstrated higher rates of endoscopic remission than either of its component treatments used alone in patients with moderate to severe Crohn’s disease, according to Phase 2a trial results announced by the pharmaceutical company.
The therapy achieved endoscopic remission in 30.2% of patients at Week 12, the study’s primary endpoint, compared with 21.3% among patients receiving the IL-23 inhibitor risankizumab and 18% among those treated with the α4β7 inhibitor trosunilimab.
The gap widened by Week 24, when remission rates reached 40.5% with ABBV-466, against 22.4% with risankizumab alone and 20% with trosunilimab alone, according to findings from the ongoing TARGET-CD study.
ABBV-466 combines risankizumab, an IL-23 inhibitor, with trosunilimab, an α4β7 inhibitor. The approach is designed to target two complementary drivers of inflammation in Crohn’s disease by suppressing inflammatory signalling and limiting the movement of immune cells into the gut.
"ABBV-466 reflects how we are building the next generation of our inflammatory bowel disease (IBD) portfolio, leveraging insights from our own research to address disease pathways that may remain active even when a central inflammatory pathway is inhibited," said Kori Wallace, vice president, global head of immunology clinical development, AbbVie.
"Our research pointed to evidence of α4β7-driven inflammation despite risankizumab's IL-23 p19 inhibition, leading us to augment risankizumab with a novel α4β7 inhibitor, trosunilimab. The TARGET-CD results reinforce our strategy of advancing therapies designed around the complex biology of Crohn's disease."
The Phase 2a platform study enrolled 300 patients with moderately to severely active Crohn’s disease, assigning them to receive ABBV-466, risankizumab or trosunilimab for 24 weeks.
The trial population included patients with varied treatment histories: 25% had never received biologic therapy, while 75% had failed at least one advanced treatment. A quarter had failed three or more advanced therapies, highlighting the treatment challenges faced by patients with difficult-to-control disease.
Beyond remission rates, gene expression analyses suggested that ABBV-466 was associated with changes in intestinal tissue linked to healing and restoration of the gut barrier.
By Week 12, researchers reported signs of colonic epithelial repair and barrier restoration. By Week 24, tissue remodelling and metabolic changes were also observed—findings generally not seen with either monotherapy.
The results suggest the dual-targeting approach may influence not only inflammatory activity but also biological processes associated with intestinal recovery. However, the findings come from an ongoing Phase 2a study and require further evaluation.
"Many patients with Crohn's disease move from one advanced therapy to the next and still have active inflammation in the bowel, even when their symptoms improve," said Remo Panaccione, Professor of Medicine and Director of the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary.
"Endoscopic remission is a goal we aim for, because ongoing inflammation can drive disease progression over time. What stands out in the TARGET-CD Phase 2a study is that a dual-targeting approach reached that goal more often than either therapy alone in a heavily pretreated population."
