More than one-half of patients with Crohn's disease treated with mirikizumab achieved clinical remission at one year, including patients with previous biologic failure.- Eli Lilly.

In Eli Lilly and Company's pivotal Phase III VIVID-1 study, patients with moderately to severely active Crohn's disease, with or without previous biologic failure, achieved statistically significant and clinically meaningful improvements across multiple clinical and endoscopic endpoints at one year with mirikizumab compared to placebo. Data from this study – the first Phase III treat-through data reported for an IL23p19 antibody – will be presented at Digestive Disease Week (DDW), held in Washington, D.C. from May 18-21.

"Crohn's disease is a complex condition that, if untreated, may result in irreversible damage to the digestive tract. Mirikizumab patients achieved high rates of combined clinical remission and endoscopic response, two important treatment targets that are difficult to achieve in the same patient, at one year. This is particularly impressive for patients with previous biologic failure who are generally considered hard-to-treat," said Bruce Sands, M.D., M.S., Dr. Burrill B. Crohn Professor of Medicine and Chief of the Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai. "Consistent results across patient populations underscore the potential impact of mirikizumab in individuals living with this condition."

As previously reported, mirikizumab achieved both co-primary endpoints and all major secondary endpoints at Week 52 compared to placebo (p<0.000001), including>: i. Proportion of participants achieving clinical response by patient reported outcomes (PRO) at Week 12 and clinical remission (defined as a Crohn's Disease Activity Index [CDAI] Total Score <150) at week 52 compared to placebo. ii. proportion of participants achieving clinical response by pro at week 12 and endoscopic response (defined as greater than 50% reduction from baseline in simple endoscopic score – crohn's disease [ses-cd] total score) at week 52 compared to placebo.>

Consistent response rates and treatment effects were observed in patients with no prior biologic failure (bio-naïve) and harder-to-treat patients with previous biologic failure: i. 39.3% of bio-naïve and 36.7% of bio-failed patients taking mirikizumab achieved composite Week 12 PRO clinical response and Week 52 endoscopic response compared to 11.8% and 6.2% of placebo, respectively. ii. 47.3% of bio-naïve and 43.4% of bio-failed patients taking mirikizumab achieved composite Week 12 PRO clinical response and Week 52 clinical remission by CDAI, compared to 26.5% and 12.4% of placebo, respectively.

At one year, clinical remission and endoscopic response were achieved by 54.1% and 48.4% of patients on mirikizumab, respectively. Notably, of the patients who received mirikizumab, 56.7% of bio-naïve and 51.2% of bio-failed patients achieved clinical remission at Week 52.

Patients taking mirikizumab achieved combined Week 52 clinical remission and endoscopic response at nominally statistically significant higher rates compared to patients on ustekinumab (34.4% versus 27.9%), with greater difference among those patients with previous biologic failure. At multiple time points, including Week 52, mirikizumab also achieved nominal statistical significance compared to ustekinumab in decreasing fecal calprotectin and C-reactive protein, two key biomarkers for inflammation. Superiority to ustekinumab was not achieved for endoscopic response.

Additionally, in the population with previous biologic failure, numerically greater rates were observed with mirikizumab compared to ustekinumab for endoscopic response, endoscopic remission (SES-CD total less than 4, a greater than 2 point reduction from baseline and no subscore greater than than 1 in any individual variable), and corticosteroid-free CDAI clinical remission at Week 52. These observed differences were not statistically significant.

The overall safety profile of mirikizumab in patients with moderately to severely active Crohn's disease was consistent with the known safety profile in patients with ulcerative colitis. The frequency of serious adverse events was greater in placebo than mirikizumab. The most common adverse events were COVID-19, anemia, arthralgia, headache, upper respiratory tract infection, nasopharyngitis and injection site reaction.

"After one year of treatment, more than one-half of patients treated with mirikizumab achieved clinical remission and nearly one-half achieved endoscopic response. Remarkably, the majority of patients who achieved either of these endpoints, achieved both together," said Mark Genovese, M.D., senior vice president of Lilly Immunology development. "Lilly is committed to developing innovative treatments, like mirikizumab, that may improve upon the standard of care for people impacted by inflammatory bowel disease and immune-mediated diseases."