Anti-IL-13 MAB fails to show results against ulcerative colitis

Last Updated: 2015-01-23

By Scott Baltic

NEW YORK (Reuters Health) - In its first such test, anrukinzumab, a humanized anti-interleukin-13 monoclonal antibody, did not show a statistically significant therapeutic effect in subjects with active ulcerative colitis (UC) compared with placebo, according to a new study.

In the phase 2a randomized, double-blind, placebo-controlled study, researchers also found that despite the lack of demonstrable therapeutic effect, anrukinzumab did appear to be binding to IL-13 as expected. Given that, "the lack of biomarker, clinical, or endoscopic response seriously questions the pathogenic role of IL-13 in UC," the authors concluded.

The study's primary endpoint was fold change in fecal calprotectin, a UC-related biomarker, from baseline to week 14. The study apparently was the first to use fecal calprotectin as a primary endpoint to investigate the therapeutic potential of a drug in the treatment of UC.

The study was also the first investigation of an anti-IL-13 therapy in subjects with active UC. It encompassed four arms: patients who received 200, 400, or 600 mg doses of anrukinzumab and patients who received a placebo, the researchers say in their January 7 online paper in Gut.

In light of the study's findings, " t is likely that increased IL-13 does not cause disease in people broadly," Dr. Scott Snapper told Reuters Health. Snapper chairs the National Scientific Advisory Committee for the Crohn's and Colitis Foundation of America and is the director of the Inflammatory Bowel Disease Center at Boston Children's Hospital and was not involved in the study.

As a good-quality study in an outstanding journal, he added, "it will majorly reduce enthusiasm for this line of research."

Snapper noted, however, that "at some of the lower doses, there were hints of things." The report highlighted what appeared to be an inverse dose response to anrukinzumab, with worse outcomes at higher doses.

The lowest dose (200 mg) demonstrated lower fecal calprotectin levels versus placebo at all time points except for week 14, with the changes statistically significant at weeks 4, 8, and 12. This inverse dose response was also seen in other clinical endpoints, though the authors cautioned that the study was not adequately powered to detect statistical differences in these exploratory outcomes.

Finally, Snapper pointed out, ulcerative colitis is a heterogeneous condition, subsuming possibly as many as five or 10 distinct diseases, so it's possible that anrukinzumab, especially given its favorable safety profile, might be useful in one or more subsets of UC patients.

The sponsor-unblinded study was conducted at 38 centers in the United States, Canada, and eight European countries. Of 84 patients 18 to 65 years old randomized into the study between March 2011 and April 2013, 57 completed the 14-week treatment phase, and 45 also completed the 18-week safety follow-up period.

Participants received anrukinzumab or placebo as five IV doses over 14 weeks, at baseline and at weeks two, four, eight, and 12.

The researchers saw no significant correlation between IL-13 levels and fecal calprotectin levels.

This research was funded by Pfizer. Seven authors report being employed by Pfizer; three authors report various relevant relationships, and three report no disclosures.

SOURCE: http://bmj.co/1t6d2NZ

Gut 2015.