Treatment with Elli Lilly’s mirikizumab led to a significant reduction in disease activity in moderate and severe Crohn’s disease patients after 12 weeks of treatment, findings from a Phase 2 trial show.
Results from the trial were recently discussed in an oral presentation at the 2019 Digestive Disease Week (DDW) medical conference in San Diego.
The treatment candidate mirikizumab is a large molecule that blocks the activity of the proinflammatory cytokine interleukin 23 (IL-23), which is believed to be increased and uncontrollably produced in Crohn’s disease patients, leading to inflammation of the gut.
The SERENITY trial (NCT02891226) is a multicenter, randomized, placebo-controlled Phase 2 study designed to evaluate mirikizumab’s safety and efficacy in adults with moderately to severely active Crohn’s disease.
Participants were randomly assigned to receive a placebo or one of three doses of mirikizumab (200 mg, 600 mg, or 1,000 mg) for 12 weeks.
The trial’s main goal is to determine the proportion of subjects achieving a 50% reduction on the Simple Endoscopic Activity Score-Crohn’s Disease (SES-CD) at 12 weeks. SES-CD evaluates the size of mucosal ulcers, the ulcerated surface and its extension, and the presence of abnormal narrowing of the gut.
Secondary objectives included clinical remission as measured by patient reported outcomes, endoscopic remission, and mirikizumab’s safety.
After approximately three months of treatment, 25.8% of patients taking 200 mg of mirikizumab, 37.5% of the 600 mg group, and 43.8% of the 1,000 mg group achieved a 50% reduction on the SES-CD, compared with 10.9% of the placebo group.
Colonoscopy examination revealed endoscopic remission (meaning there’s no significant narrowing and ulceration of the bowel) was achieved in 6.5%, 15.6%, and 20.3% of patients treated with 200 mg, 600 mg, and 1,000 mg of mirikizumab, respectively, compared with 1.6% of the placebo sample.
Around 12.9%, 28.1% and 21.9% of patients treated with 200 mg, 600 mg, and 1,000 mg of mirikizumab, respectively, achieved remission based on patient reported outcomes, compared with 6.3% of the placebo group. In this case, remission was defined as an average daily stool frequency of less than or equal to 2.5, and abdominal pain less than or equal to one.
Regarding the therapy’s safety, 4% (five patients) of all participants on mirikizumab reported one or more serious side effect, and 64% (81 patients) said they had one or more treatment emergent adverse event after their first dose administration, which included headaches, weight gain, and common cold (nasopharyngitis). In comparison, 11% (seven patients) of the placebo sample reported one or more serious adverse event, and 70% (45 patients) reported one or more treatment emergent adverse event.
“Mirikizimab may have the potential to be a valuable addition to the available treatment options for Crohn’s disease because of the endoscopic and symptomatic responses seen in this trial across all doses,” Bruce E. Sands, MD, MS, chief of the Dr. Henry D. Janowitz Division of Gastroenterology at the Icahn School of Medicine at Mount Sinai and lead investigator of the study, said in a news release.
SERENITY’s maintenance phase is ongoing, and participants will be followed for up to two years.
Mirikizimab is also being studied as a therapy for ulcerative colitis in several clinical trials.
“Following last year’s presentation of positive Phase 2 results for mirikizumab for the treatment of moderate to severe ulcerative colitis, we are excited to return to DDW to present more positive data for mirikizumab in patients with chronic, inflammatory gastrointestinal conditions,” said Lotus Mallbris, MD, PhD, vice president of immunology development at Eli Lilly and Company.
“As we continue to advance the science of gastroenterology, we are hopeful that mirikizumab helps us raise the standard and make remission possible for people living with immune-mediated diseases like Crohn’s disease. Physicians want objective signs of improvement to be able to convey to patients that they are getting better, and data from this study suggest mirikizumab may address this need. We look forward to initiating Phase 3 trials to further evaluate mirikizumab’s benefit-risk profile for the treatment of Crohn’s disease,” Mallbris added.