NASHVILLE, Tenn. — Treatment of moderate-to-severe ulcerative colitis (UC) with the first-in-class oral interleukin (IL)-23 inhibitor drug icotrokinra showed high rates of response and remission over 76 weeks, with a favorable safety profile, according to the long-term results of a phase 2b study.

"The big advance here is to have an oral agent, icotrokinra, that can inhibit IL-23 very well and is quite effective with a once-a-day dose," said first author Maria T. Abreu, MD, of Cedars-Sinai in Los Angeles, in a press statement for the study, presented at the American College of Gastroenterology (ACG) 2026 Annual Scientific Meeting. 

"Often patients with inflammatory bowel disease hate having to give themselves shots or infusions, no matter how infrequent these are," she noted. "Therefore, a medication that can deliver efficacy that seems comparable to that seen with the parenteral forms of IL-23 inhibitors is terrific for patients."

Initial Results of ANTHEM-UC 

IL-23 inhibitors have shown favorable efficacy and safety in the treatment of advanced UC; however, the drugs involved intravenous or subcutaneous injection, which can be burdensome to patients, particularly over the long-term.

Oral icotrokinra was approved earlier this year by the FDA, under the brand name Icotyde (Johnson & Johnson), for the indication of plaque psoriasis, which — like UC — is also an immune-mediated inflammatory disorder involving the IL-23 pathway.

In the phase 2b, randomized, double-blind ANTHEM-UC trial, 252 patients with moderately to severely active UC were randomized 1:1:1:1 to treatment either with once-daily oral icotrokinra at doses of 100 mg, 200 mg, or 400 mg, or placebo, with groups stratified by prior intolerance to advanced therapy and by a Mayo endoscopy subscore of at least 2, indicative of higher inflammation of the colon.

In initial results from the trial, presented at previous medical meetings and being published this week in The New England Journal of Medicine, icotrokinra at all three doses studied met the primary endpoint of significant improvements in clinical, endoscopic, and histologic endpoints at week 12.

At week 16, those who had an inadequate response had a blinded treatment adjustment, and the placebo group was switched to icotrokinra 400 mg daily. 

Those achieving a clinical response at week 28 continued on their treatment in the long-term extension study, with initiation of corticosteroids, immunomodulators, or 5-aminosalicylic acid anti-inflammatory therapies permitted at that point. 

Long-Term Extension Study 

Of the 136 patients who entered the extension study — including 48 who received 100 mg icotrokinra and two groups of 44 who individually received 200 mg or 400 mg — 85% remained on treatment through week 76­.

The majority of participants who remained on treatment — 81.3% in the 100 mg group and 72.7% in both the 200 and 400 mg groups — achieved clinical response, defined as a decrease from baseline in the modified Mayo score by ≥ 30% and ≥ 2 points, with either a ≥ 1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1.

Clinical remission, defined as a stool frequency subscore of 0 or 1, rectal bleeding subscore of 0, and Mayo endoscopy subscore of 0 or 1, was achieved at week 76 by 56.3%, 59.1%, and 56.8%, respectively, in the three treatment groups.

Of note, as many as 97% of those achieving clinical remission at week 76 were corticosteroid-free at that time point. 

Endoscopic improvement, defined as a Mayo endoscopy subscore of 0 or 1, was further observed at rates of 64.6%, 68.2%, and 63.6%, respectively, across the three doses.

Importantly, symptom remission, defined as a stool frequency subscore of 0 or 1 and rectal bleeding subscore of 0, was observed as early as week 4 and was maintained or improved through week 76 in nearly 80% of patients.

Similar improvements were seen across the outcomes in patients with prior inadequate responses or intolerances to advanced therapies.

Safety Profile Is Key 

The drug was well tolerated, with 85% of patients remaining on treatment through the final analysis in week 78.

No new safety signals were identified in the long-term extension, with no adverse events and serious adverse events, including infections, or deaths being reported.

One case of an in situ ductal breast carcinoma, not related to the study intervention, was reported in the 100 mg group during the long-term extension.

The importance of inhibition of IL-23 "is that it appears to be quite safe in terms of not increasing the risk of infections or cancer," Abreu explained in the press statement.

And "here we have a drug that is oral, works quickly, and is as safe as all the IL-23 inhibitors that have been studied so far," she told Medscape Medical News. "I therefore think it's a good option for patients as their first advanced therapy." 

While a small drop-off or no further increase in symptom remission was observed at the end of the 76-week extension period, "compared to things like the anti-TNFs that have a high rate of patients losing response, this looks very promising," Abreu said.

'Impressive' Efficacy and Safety 

Commenting on the study, Russell D. Cohen, MD, a professor of medicine at the Pritzker School of Medicine and co-director of the Digestive Diseases Center at the University of Chicago, echoed the importance of the safety profiles observed with IL-23 therapies in UC, as well as in Crohn's disease.

"The safety of the IL-23 inhibitors is really outstanding in the clinical trials, with no substantial signals for infections, cancers, major adverse cardiac events, or blood clots, that have been concerns with other agents," he explained.

"That's why they've taken off as the treatment of choice for many patients with [moderate-to-severe] Crohn's disease and ulcerative colitis."

To see similar efficacy and safety with all the doses of the oral formulation is "impressive," he added, particularly with notable benefits, such as patients no longer needing corticosteroids.

"For many years, the only effective therapy [for these conditions] were corticosteroids, which can have horrible side effects, and they don't actually keep people well over the long term, so these phase 2 results are very encouraging," Cohen said.

While the ANTHEM-UC trial did not include patients with Crohn's disease, Cohen noted that "we're looking forward to seeing the phase 3 studies of the class also involving patients with Crohn's disease, and we hope to see the same excellent efficacy and the safety that we've seen with the injectable IL-23 therapies."

The study was funded by Johnson & Johnson. Abreu is on the advisory committee and speakers bureau and is a board member for Johnson & Johnson. Cohen disclosed that he is a consultant and speaker for Johnson & Johnson. Both Abreu and Cohen also have advisory and/or relationships with many of Johnson & Johnson's competitors.