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• Posted September 27, 2024

Treatment Could Be New Option for People Battling Ulcerative Colitis

An experimental monoclonal antibody treatment appears to ease the digestive disorder ulcerative colitis in patients who've failed other medications, a new trial shows.

The treatment, tulisokibart, spurred remission of symptoms in more than a quarter of patients, compared to only 1.5% of those taking a placebo, an international group of researchers reported Sept. 26 in the New England Journal of Medicine.

Ulcerative colitis affects over 900,000 Americans and is a form of inflammatory bowel disease (IBD). The exact causes of the illness remain unknown, but ulcerative colitis can be disabling, causing stomach cramps, diarrhea, weight loss and rectal bleeding.

The new trial was funded by Prometheus Biosciences, which is developing tulisokibart. Researchers are hoping the drug might offer patients a valuable new treatment option.

“Findings from this study are poised to have a remarkable impact on treatment for ulcerative colitis and IBD overall,” said study senior author Dr. Stephan Targan. He's a professor of medicine at Cedars-Sinai in Los Angeles and director of Cedar Sinai's Inflammatory Bowel Disease (IBD) Center.

As the researchers explained, a protein called TL1A appears to exacerbate ulcerative colitis, and tulisokibart is thought to work by mimicking the effect of natural antibodies that target TL1A.

The monoclonal antibody thereby reduces inflammation and fibrosis (a stiffening of tissues) that lies behind many ulcerative colitis symptoms.

“Managing ulcerative colitis often requires a personalized approach and ongoing adjustments based on the patient’s response to therapy, especially for patients with more severe cases,” noted lead investigator Dr. Bruce Sands, a professor of medicine at the Icahn School of Medicine at Mount Sinai in New York City.

“Tulisokibart offers a new potential treatment option and addresses a critical gap in treatments for ulcerative colitis," he said in a Mount Sinai news release.

The 12-week trial involved two cohorts, all people with ulcerative colitis who'd been taking steroids long-term or had failed other conventional and/or advanced therapies.

In the first cohort, 135 patients were randomly selected to either intravenous tulisokibart (1,000 milligrams (mg) on day 1 and 500 mg at weeks 2, 6, and 10) or a "dummy" placebo.

More than a quarter (26.5%) of folks who got the new therapy went into remission by week 12, the researchers reported, compared to just 1.5% of those on placebo.

In a second cohort, Sands and colleagues first had 43 patients undergo a specially designed diagnostic test to assess their suitability for tulisokibart. Another 32 patients had been selected using the test in the first group of patients, as well.

Among the 75 patients who got the new "Dx-positive" diagnostic assessment, 31.6% achieved remission of their disease by week 12, compared with 10.8% of those who got the placebo.

The Dx-positive test should prove very useful in the future, said study co-author Dr. Dermot McGovern.

“Previously, we have only been able to prescribe a medication to a patient that we think will work well, but going forward we could imagine telling the patient, ‘Actually, the genetic test suggests that you would be more likely to respond to this therapy,’” said McGovern, who directs translational research in the F. Widjaja Inflammatory Bowel Disease Institute at Cedars-Sinai.

In terms of side effects, 46% of patients in the tulisokibart group and 43% in the placebo group had some type of "adverse event," although most events were rated as mild to moderate in severity.

How is the new therapy different?

“Unlike other IBD treatments that can exacerbate inflammation or suppress the body’s natural anti-inflammatory responses, our findings suggest that tulisokibart modulates inflammation and the body's anti-inflammatory mechanisms,” Targan explained. “This dual action could lead to more balanced and effective management of ulcerative colitis.”

Tulisokibart "was generated based on the concept of precision medicine," he added. "It shows promise as being both anti-inflammatory and anti-fibrotic; it represents a potential turning point in drug development and discovery; and it could change how this complex disease is treated in the future."

A phase 3 trial is planned that will further examine safety and test the effectiveness of tulisokibart in patients who take it longer than 12 weeks.

More information

Find out more about ulcerative colitis at the National Institute of Diabetes and Digestive and Kidney Diseases.

SOURCES: Cedars-Sinai, news release, Sept. 26, 2024; Mount Sinai Health System, news release, Sept. 26, 2024