Ulcerative Colitis Drug Doubles Remission Rates in Clinical Trial

A new drug doubled the rate of remission in patients with ulcerative colitis (UC), an inflammatory bowel disease, in two Phase 3 clinical trials. The research is published in The New England Journal of Medicine.

Addressing a high unmet need

An estimated 600,000–900,000 people in the U.S. live with UC, and the number of people with the disease is steadily growing worldwide.

UC is a chronic inflammatory disease that affects the lining of the colon causing bloody diarrhea, abdominal pain, anemia and fatigue, and those with the disease are also at a higher risk of colorectal cancer. The causes of UC are not well understood, but it is thought to be a result of multiple factors such as abnormal immune system reactions in the gut.

UC patients can go through periods of flare-ups – where symptoms worsen – and remission – in which their symptoms improve. Medications can go some way to control the disease and help bring about remission – which can last from weeks to months or even years – but current treatments are not always successful, requiring some patients to undergo surgery to remove part or even all of the colon.

“There is still a high unmet need for safe and effective treatments for [UC]. This new medicine meets this need for an important proportion of patients,” said Geert D’Haens, lead author of the study and professor of gastroenterology at Amsterdam University Medical Centers.

A recent Phase 2 clinical trial showed that a new drug, mirikizumab, was effective in patients with UC. This antibody-based drug binds to and blocks the activity of interleukin-23, a protein that triggers and maintains gut inflammation linked to both UC and Crohn’s disease. Now, researchers report the results of two Phase 3 studies that investigated the efficacy and safety of mirikizumab in 1,281 patients with active, moderate-to-severe UC.

Increased remission rates

D’Haens and colleagues conducted two randomized, double-blind and placebo-controlled Phase 3 trials.

The first, called LUCENT-1, treated UC patients with infusions of either 300 mg of mirikizumab (868 patients) or a placebo (294 patients) every 4 weeks over a 12-week period. Of these, 544 responded to the therapy, and mirikizumab-treated patients were significantly more likely to achieve clinical remission, with 24.2% of patients in the mirikizumab group achieving remission compared to 13.3% in the placebo group.

The 544 patients who successfully responded to the therapy were moved into the second study, LUCENT-2, in which they received subcutaneous injections of either 200 mg mirikizumab (365 patients) or placebo (179 patients) every 4 weeks for an additional 40 weeks. Here, 49.9% of the treated patients achieved clinical remission compared to 25.1% of patients who received a placebo – another significant increase.

Patients who received mirikizumab also had increased rates of endoscopic remission (reduced signs of disease on endoscopy) and less bowel movement urgency. Common colds and joint pain were more commonly reported with mirikizumab treatment across both trials, while 15 treated patients experienced opportunistic infections such as herpes zoster (shingles).

Of note, cancer also occurred in a small number of mirikizumab-treated patients: “Among the 1,217 patients treated with mirikizumab during the controlled and uncontrolled periods (including the open-label extension and maintenance periods) in the two trials, 15 had an opportunistic infection (including 6 with herpes zoster infection) and 8 had cancer (including 3 with colorectal cancer). Among the patients who received placebo in the induction trial, 1 had herpes zoster infection and none had cancer,” the authors write in the paper.

The authors also state that additional, long trials are ongoing to investigate the safety and efficacy of mirikizumab in UC patients. Nonetheless, the findings from the current trials suggest that the drug holds promise for the treatment of UC: “If we combine these results together, we see that mirikizumab is an effective drug for those patients with moderately severe and severe forms of [UC]. We hope that it will be available as a treatment option in Europe this year,” said D’Haens.

Reference: D’Haens G, Dubinsky M, Kobayashi T, et al. Mirikizumab as induction and maintenance therapy for ulcerative colitis. 2023. NEJM. doi: 10.1056/NEJMoa2207940

This article is a rework of a press release issued by Amsterdam University Medical Centers. Material has been edited for length and content.