, according to new findings from the phase 3 LUCENT-1 induction and LUCENT-2 maintenance trials. The findings were reported in the New England Journal of Medicine.
Mirikizumab manufacturer Eli Lilly, which funded the study, is hoping the drug will become the first IL-23 inhibitor to be approved in the United States for ulcerative colitis. The drug targets the p19 subunit that is unique to IL-23. Ustekinumab, which targets the p40 subunit that is shared by IL-12 and IL-23, has been approved for UC and Crohn’s disease. Risankizumab, which targets the IL-23 p19 subunit, has been approved for Crohn’s treatment.
Earlier this year, the Food and Drug Administration rejected Lilly’s mirikizumab application over manufacturing issues, with no concerns about the clinical data, safety, or labelling. The company said it was working with the FDA to resolve the concerns, and hopes to “launch mirikizumab in the U.S. as soon as possible.” The drug has already been approved in Japan for moderately and severely active ulcerative colitis, and the drug was reviewed favorably by the European Medicines Agency.
Since 2014, the market size of interleukin inhibitors has grown fivefold with the greatest share belonging to IL-23 inhibitors.
The induction trial included 1,281 patients with moderately or severely active ulcerative colitis (UC), and 544 patients who had a response to mirikizumab were randomized again in the maintenance phase.
Significantly more patients in the mirikizumab arm – 24.1% (P < .001) – had clinical remission at week 12, although there was a high placebo remission rate, as is often seen in UC trials, at 13.3%. At week 40 of the maintenance trial, 49.9% of those on mirikizumab had clinical remission, compared to 25.1% for placebo (P < .001).
Mirikizumab also performed better than placebo on the trial’s five secondary endpoints: glucocorticoid-free clinical remission (44.9% to 21.8%), maintenance of clinical remission (63.6% to 36.9%), endoscopic remission (58.6% to 29.1%), histologic-endoscopic mucosal remission (43.3 %), and bowel-urgency remission (42.9% to 25.0%) (P < .001 for all).
Researchers led by Geert D’Haens, MD, PhD, professor of gastroenterology at Amsterdam University Medical Centers, emphasized the effects on acute inflammatory cell infiltration.
“Current recommendations for the treatment of ulcerative colitis include increasingly rigorous goals beyond symptomatic or endoscopic improvement,” the authors wrote. “Recent literature has recommended the absence of intraepithelial neutrophils as a minimal requirement for remission on the basis of histologic testing. After 1 year of mirikizumab treatment, more than 40% of the patients in the LUCENT-1 and LUCENT-2 trials had no mucosal neutrophils. “
Urgency NRS (Numeric Rating Scale) – a measure developed by Lilly in which patients report the urgency of bowel movements over the previous 24 hours – was used in the trial.
“Many patients with ulcerative colitis consider control of bowel movements to be more important than rectal bleeding or stool frequency,” the researchers said. “In the induction trial, patients reported reductions in bowel urgency with mirikizumab therapy, which were sustained during the maintenance trial.”
Of the 1,217 patients treated with mirikizumab during the placebo-controlled and non–placebo-controlled periods, opportunistic infections were seen in 15, with 6 herpes zoster infections. One case of an opportunistic infection was seen in a patient receiving placebo in the induction trial.
Cancer was seen in eight of the mirikizumab-treated patients, with adenocarcinoma of the colon in two patients in the induction trial. No cancers were seen in patients receiving placebo in induction.
“Additional and longer trials are ongoing,” the researchers said, “to further assess the efficacy and safety of mirikizumab therapy in patients with ulcerative colitis.”
The authors disclosed consultancies, or other relationships, with a number of pharmaceutical companies, including Eli Lilly, the maker of mirikizumab.
