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ORLANDO -- For patients diagnosed with moderate to severe ulcerative colitis, the investigational agent icanbelimod had mixed results in reducing the severity of disease within 12 weeks when used as induction and maintenance therapy in an early, dose-ranging study.

The adapted Mayo score for ulcerative colitis (excluding physician global assessment) declined an average of 2.60 points for icanbelimod-treated patients compared with a decline of 1.95 points on the 9-point scale in the placebo group (P=0.094), reported Jiaming Qian, MD, of Peking Medical University Hospital in Beijing, in a poster presentation at the Advances in Inflammatory Bowel Diseases annual meeting.

While that primary endpoint was missed, the secondary endpoint was met with a 3.67-point decline in the complete Mayo score among patients on icanbelimod compared to a decline of 2.74 points among the patients on placebo (P=0.044). A 3-point change on this 12-point scale is considered .

"Most clinical responders at week 12 demonstrated continued efficacy with 36 weeks of maintenance therapy," Qian reported. Based on Mayo score changes, 28 of the 53 icanbelimod-treated patients were designated as responders, and 21 of those patients elected to continue icanbelimod another 36 weeks, for 48 weeks in total.

In that group, at week 48, Qian reported that 61.9% of the patients were responders, 57.1% achieved clinical remission, and 57.1% achieved mucosal healing.

"Our findings suggest that patients with ulcerative colitis would likely derive greater clinical benefit with higher doses than icanbelimod 0.2 mg daily, the maximum administered in this phase II dose-ranging trial, which will thus be investigated in the phase III trial program," Qian reported.

The patients in the study were recruited from 64 study centers in China, Pakistan, Ukraine, and the U.S. The participants averaged around age 42 years, 92% were Asian, and 63% were men.

Icanbelimod is a next-generation sphingosine 1-phosphate (S1P) receptor modulator with no notable activity for S1P3, a subtype associated with safety concerns, the researchers noted. The trial enrolled individuals with moderate-to-severe ulcerative colitis defined as an adapted Mayo score of 4 or greater and an endoscopic subscore of 2 or greater. They were randomized in a double-blind fashion to receive icanbelimod at a dose of 0.1 or 0.2 mg or placebo once daily orally. Study medication was administered within 30 minutes of breakfast.

Clinical response was defined as a drop in adapted Mayo score by at least 2 points and 30% from baseline, plus a decrease in rectal bleeding subscore of at least 1 or drop to an absolute subscore of 1 point or less, at week 12. Clinical remission required a stool frequency subscore of no more than 1, rectal bleeding subscore of 0, and endoscopic subscore of 1 or less.

Qian reported that the treatment was well tolerated. Adverse effects -- mainly grade 1 events -- were experienced by 88% of the patients on icanbelimod 0.2 mg, by 94% of the patients on icanbelimod 0.1 mg, and by 71% of patients on placebo. None of the adverse events in the study were fatal. There were two serious adverse events in the 0.2 mg icanbelimod patients, six in the icanbelimod 0.1 mg group, and three in the placebo group. Three of the adverse reactions in the icanbelimod cohorts were considered drug-related.

"In this trial, orally administered icanbelimod was well tolerated and significantly improved key outcomes, including the complete Mayo score, clinical response, and clinical remission at week 12," Qian stated.

In commenting on the study, Julian Remouns, DO, a gastrointestinal fellow at Lankenau Hospital/Main Line Health in Wynnewood, Pennsylvania, told MedPage Today, "This drug, icanbelimod, appears to be similar in mechanism of action with other S1P receptor modulators. While the information presented here looks promising, the caveat is that this is a phase II trial and we need to see further development with this drug before we can tell what that promise will be."

"However, it is always good to have more weapons when combatting these diseases," Remouns added.

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