Mirikizumab Achieves Primary Endpoints in Phase 3a Trial for Crohn Disease

Lotus Mallbris, MD, PhD

Credit: Society for Women's Health Research

Eli Lilly and Company has announced positive topline results from the phase 3a VIVID-1 study of mirikizumab for adults with moderately to severely active Crohn disease (CD).

Announced on October 12, 2023, results showed 54.1% of patients treated with mirikizumab achieved clinical remission at week 52 compared to 19.6% of patients who received placebo, with mirikizumab demonstrating non-inferiority versus ustekinumab as an active comparator.¹

"I'm excited by these results, which showed more than half of patients on mirikizumab achieved clinical remission as measured by [Crohn's Disease Activity Index] at one year. Furthermore, mirikizumab demonstrated robust efficacy across subgroups and particularly in patients for whom prior biologic therapy had failed," said Lotus Mallbris, MD, PhD, senior vice president of immunology development at Lilly.¹

An investigational interleukin-23p19 antagonist, mirikizumab selectively targets the p19 subunit of interleukin-23 and inhibits the interleukin-23 pathway to prevent the pathogenesis of ulcerative colitis (UC) and CD. It is currently indicated for the treatment of moderately to severely active UC in Japan, Germany, the United Kingdom, and Canada.¹

A randomized, double-blind, placebo- and active-controlled treat-through trial, VIVID-1 evaluated the safety and efficacy of mirikizumab for the treatment of CD in adult patients. To be included in the study, patients were required to have a diagnosis of CD for ≥3 months prior to baseline and demonstrate intolerance, loss of response, or inadequate response to conventional or biologic therapy for CD.²

In total, 1158 participants were enrolled in VIVID-1 and assigned to mirikizumab, ustekinumab, or placebo treatment arms. All patients in the active treatment arms from the 12-week induction period continued with their original mirikizumab therapy into the maintenance portion of the study up to week 52. Placebo patients who did not achieve clinical response at week 12 were switched to blinded mirikizumab treatment.^1,2

The trial had coprimary endpoints, including the proportion of participants achieving clinical response at week 12 and clinical remission at week 52 and the proportion of participants achieving clinical response at week 12 and endoscopic response at week 52.¹

According to the release, a statistically greater proportion of patients in the mirikizumab arm achieved clinical response at week 12 and clinical remission at week 52 compared to placebo (45.4% versus 19.6%, P <.000001). Additionally, more patients treated with mirikizumab achieved clinical response at week 12 and endoscopic response at week 52 compared to those on placebo (38.0% versus 9.0%, P <.000001), although mirikizumab did not achieve superiority to ustekinumab for the endpoint of endoscopic response.¹

The overall safety was consistent with the known safety profile of mirikizumab. The most common treatment-emergent adverse events reported among patients treated with mirikizumab were COVID-19, anemia, arthralgia, headache, and upper respiratory tract infection. Additional adverse events of interest included infections, injection-site reactions, hypersensitivity, liver enzyme elevations, depression, and suicidal thoughts.¹

The release noted data from VIVID-1 will be used to support a marketing application for mirikizumab in CD to the US Food and Drug Administration and other regulatory agencies in 2024.¹

References:

1. Lilly. Lilly's Mirikizumab Helped Patients with Crohn's Disease Achieve Long-Term Remission in Phase 3 Trial. News Release. October 12, 2023. Accessed October 12, 2023. https://investor.lilly.com/news-releases/news-release-details/lillys-mirikizumab-helped-patients-crohns-disease-achieve-long
2. Clinicaltrials.gov. A Study of Mirikizumab (LY3074828) in Participants With Crohn's Disease (VIVID-1). October 11, 2023. Accessed October 12, 2023. https://clinicaltrials.gov/study/NCT03926130?cond=Crohn%27s%20Disease&intr=Mirikizumab&rank=3