DAY 3 - Investigational Therapy Shows Promise in the Treatment of Moderate to Severe Ulcerative Colitis

A monoclonal antibody with a novel mechanism of action may help patients with ulcerative colitis (UC) achieve and maintain clinical remission and endoscopic improvement of disease even when administered in low doses, according to a study presented at the ACG 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania.

“There is still a need for continued evolution and novel therapeutic approaches in inflammatory bowel disease,” said Jessica R. Allegretti, MD, MPH, Director of the Crohn's and Colitis Center at Brigham and Women's Hospital, in Boston, Massachusetts. Allegretti presented findings related to the efficacy and safety of RO7790121, a fully human monoclonal antibody against TL1A, in a plenary session.

TL1A, a cytokine that plays a role in inflammatory diseases and mucosal immunity, has been implicated in the pathogenesis of inflammatory bowel disease (IBD) and intestinal fibrosis.  RO7790121 relies on a novel mechanism of action against IBD activity, which prevents the binding and subsequent signaling of TL1A to its receptor DR3 on immune cells.  
The TUSCANY-2 study, a randomized, double-blind, placebo-controlled, dose-ranging phase 2b study, was designed to evaluate the efficacy and safety of this agent in adults with UC. The trial enrolled 245 individuals aged 18 to 75 years with moderately to severely active UC, defined as a total Mayo score (tMS) of 6 or greater and an endoscopic subscore of at least 2, who had previously failed at least one conventional or advanced therapy.

In the induction period, participants received one of three doses (50 mg, 150 mg, or 450 mg) of RO7790121 or placebo. The induction period was followed by a 52-week maintenance period, during which patients received the same dose as before or a lower dose. Those who previously received placebo were randomized to one of the three doses of the monoclonal antibody. Participants were followed up for a period of 12 weeks after the end of the study.

“Treatment with RO7790121 resulted in notable improvements in efficacy endpoints,” Allegretti said. “Clinically meaningful improvements [reflected] in clinical remission by tMS, mMS, as well as endoscopic improvements were seen across all doses versus placebo at week 14, and these were sustained through week 56.”

The study did not meet its primary efficacy endpoint of remission by tMS at week 14. Although there were higher rates of clinical remission with all three doses compared with placebo, the differences were not statistically significant. However, when looking at the modified Mayo Score (mMS) at week 14, higher proportions of patients treated with all three doses achieved clinical remission compared with those in the placebo arm.
 
The rates of endoscopic improvement at week 14 were greater in the participants who received the monoclonal antibody than in those in the placebo arm, and were sustained up to week 56. Treated participants also experienced substantial decreases in fecal calprotectin between baseline and week 12, regardless of administered dose, compared with people who received placebo during induction.

“Results from the phase 2b TUSCANY-2 dose-ranging study suggest that RO7790121 has a favorable benefit-risk profile, with clinically meaningful improvements in participants with moderately to severely active UC,” Allegretti concluded.