A new analysis of the pivotal phase 3 LUCENT-1 and LUCENT-2 trials shows that the investigational interleukin-23 inhibitor mirikizumab improved quality of life in patients with ulcerative colitis after a 12-week induction period as well as after 40 weeks of maintenance therapy.
In mid-April, the FDA issued a complete response letter for mirikizumab related to manufacturing issues, but in a release on the letter, Lilly noted that the agency cited no concerns related to the drug’s safety, clinical data or labeling. Patrik Jonsson, the president of Lilly Immunology USA, reported that company representatives are “working diligently with the FDA [to resolve the manufacturing issues] and hope to launch mirikizumab in the US as soon as possible.”
Mirikizumab’s mechanism of action has the potential to set it apart from other ulcerative colitis drugs because it only targets IL-23, specifically the p19 subunit. Other drugs, such as ustekinumab (Stelara, Janssen), target both IL-12 and IL-23, noted Raymond K. Cross, MD, MS, who was not involved in the study. “What we’ve learned from dermatology is we think that the drugs that only block IL-23 are more effective. That has not been proven yet in Crohn’s and colitis, but in dermatology, it seems to be true,” said Dr. Cross, the director of the IBD program at the University of Maryland School of Medicine and co-director of the Digestive Health Center at the University of Maryland Medical Center, in Baltimore.
The new analysis, which was presented at the 2023 Canadian Digestive Diseases Week, evaluated quality of life based on responses to the Inflammatory Bowel Disease Questionnaire (IBDQ) among participants in the LUCENT-1 and LUCENT-2 studies.
The phase 3, double-blind, 12-week LUCENT-1 trial included 1,162 patients who were randomized 3:1 to undergo an induction phase of 300 mg of mirikizumab or placebo intravenously once every four weeks for 12 weeks. A total of 544 mirikizumab-treated patients achieved a clinical response during the induction phase, as defined by the modified Mayo Endoscopic Score. The responders then were randomized 2:1 to receive 200 mg of subcutaneous mirikizumab or placebo once every four weeks for the 40-week maintenance phase (LUCENT-2).
Treatment with mirikizumab led to a greater improvement in IBDQ total and domain scores at weeks 12 and 40. The risk difference for an IBDQ response was 17.1% (95% CI, 10.7%-23.5%) at the end of the induction phase and 29.5% (95% CI, 21.0%-37.9%) at week 40 of the maintenance phase. More patients in the mirikizumab groups than in the placebo group achieved IBDQ remission at week 12 (risk difference, 18.1%; 95% CI, 11.8%-24.4%; P<0.001) and week 40 (risk difference, 28.5%; 95% CI, 20.1%-37.0%; P<0.001).
Dr. Cross told Gastroenterology & Endoscopy News that he believes the new drug holds promise. “I think the data look quite good for this treatment. Whether it is better than what we have will have to be borne out in the real world when we get a sense of how the drug works in patients not in clinical trials. Maybe there will be head-to-head studies with some of [the available] therapies to get a sense of what is best. But in addition to effectiveness, one of the major advantages of these drugs is that they are incredibly safe. They do not increase your risk of any types of paradoxical autoimmune reactions or cancer. There is a very low risk of infection, so we’re looking forward to having this drug come to market and being able to use it in clinical practice,” he said.
Physicians have various therapeutic options to tailor drugs to individual patients. “I tend to use anti–IL 12/23 agents in patients who are less sick in the outpatient setting, because their onset of action may be slower, or in patients where drugs like an anti-TNF [tumor necrosis factor] or JAK inhibitors may be riskier. Also, anti–IL 12/23 agents should be first line for patients with certain dermatologic conditions like psoriasis. Mirikizumab and other anti–IL 12/23 agents would be great drugs for an ulcerative colitis patient who is less sick and has concurrent psoriasis,” Dr. Cross said.
Another plus for mirikizumab is the convenience factor, Dr. Cross said, noting that dosing transitions to a monthly subcutaneous dose after the initial intravenous dose.
—Jim Kling
Dr. Cross reported financial relationships with AbbVie, Adiso, Bristol Myers Squibb, CorEvitas, Fresenius Kabi, Fzata, Magellan, Pfizer, Samsung, Sebela and Takeda.
This article is from the May 2023 print issue.