Bruce Sands, MD: Phase 3 Treat-Through Data for Mirikizumab in Crohn’s Disease

Phase 3 data from the VIVID-1 study of mirikizumab in patients with moderately to severely active Crohn's disease with or without previous biologic failure support the selective IL-23p19 monoclonal antibody’s ability to induce clinical remission and endoscopic response in this patient population.¹

Findings were presented at Digestive Disease Week (DDW) 2024 in Washington, DC, signifying the first phase 3 treat-through data reported for an IL-23p19 antibody, and showed nearly half of patients on mirikizumab achieved endoscopic response at 52 weeks, most of whom were also in clinical remission.¹

Eli Lilly and Company previously reported that mirikizumab achieved both co-primary endpoints and all major secondary endpoints at week 52 compared to placebo (P <.000001), with consistent response rates and treatment effects observed in patients with no prior biologic failure and harder-to-treat patients with previous biologic failure.^1,2

At 1 year, clinical remission and endoscopic response were achieved by 54.1% and 48.4% of patients on mirikizumab, respectively. Of note, of the patients who received mirikizumab, 56.7% of bio-naïve and 51.2% of bio-failed patients achieved clinical remission at week 52.¹

Compared to patients taking ustekinumab, patients taking mirikizumab achieved combined week 52 clinical remission and endoscopic response at statistically significant greater rates (34.4% vs 27.9%). Mirikizumab also achieved statistical significance compared to ustekinumab for decreasing fecal calprotectin and C-reactive protein at multiple time points, although superiority was not achieved for endoscopic response.¹

Investigators noted the overall safety profile of mirikizumab was consistent with its known safety profile in patients with ulcerative colitis, for which the selective IL-23p19 monoclonal antibody is already approved.³ The most common adverse events were COVID-19, anemia, arthralgia, headache, upper respiratory tract infection, nasopharyngitis, and injection site reaction, and the frequency of serious adverse events was greater in placebo than mirikizumab.¹

For further insight into the use of mirikizumab in Crohn’s disease and the VIVID-1 trial, HCPLive spoke with Bruce Sands, MD, Dr Burrill B. Crohn Professor of Medicine at Mount Sinai.

HCPLive: Can you explain our current understand of mirikizumab, especially regarding its use in Crohn’s disease, going into VIVID-1?

Sands: Mirikizumab is an anti-p19 antibody, which blocks only IL 23. So we've had Stelara, which is ustekinumab, which blocks p40 which is found in IL 23, but found as well on IL 12, so ustekinumab blocks IL 12 and 23. Mirikizumab, like a number of other anti-p19 antibodies being investigated or approved in inflammatory bowel disease, only blocks IL 23.

It had been studied in Crohn's disease in a phase 2 study that we actually published a couple of years ago now, and it clearly showed that IV induction was effective in inducing remission and response and all the other outcomes in Crohn's disease, and seemed to have maintenance value as well. There were a number of maintenance strategies previously explored, which included either IV maintenance or subcutaneous maintenance. All of it seemed to work well, so the natural extension was to study it in phase 3, and that was the VIVID-1 study.

HCPLive: What were some of the key findings from VIVID-1?

Sands: The study was very rigorously performed and was one of the largest phase 3 Crohn’s studies ever done. There were over 1000 patients, because not only were they comparing the drug to placebo, but also sort of independently, they were comparing to ustekinumab.

The primary outcome was comparison to placebo, for those complex composite outcomes. And it was clearly superior to placebo in all those outcomes and all the key secondary outcomes. Another part of it was designed to assess noninferiority to ustekinumab. It was also designed for superiority on endoscopic response at a year. That, unfortunately, was not met and didn't achieve statistical significance, although numerically there was about a 5% advantage over plus over ustekinumab.

A lot of focus has been on the comparison to ustekinumab, but actually, really what we should take away is that the drug is highly effective, both in bio-naive and in advanced therapy-experienced patients in comparison to placebo, clearly, and is at least as good as ustekinumab.

If you dive down more deeply into the various outcomes, you find that actually when you look at more refractory patients who had failed advanced therapies, it looked like it was more advantageous in those sicker, more experienced patients.

This is obviously with intent for approval in Crohn's disease, but we know already that the anti-IL 23s are effective for treating Crohn's disease. The results are, in that sense, not surprising.

Sands has relevant disclosures with Johnson & Johnson, Abbvie, Amgen, Takeda, Lilly, and others.

References:

1. ^{Lilly. More than one-half of patients with Crohn's disease treated with Lilly's mirikizumab achieved clinical remission at one year, including patients with previous biologic failure. News Release. May 21, 2024. Accessed May 31, 2024. https://investor.lilly.com/news-releases/news-release-details/more-one-half-patients-crohns-disease-treated-lillys-mirikizumab}
2. ^{Brooks, A. Mirikizumab Achieves Primary Endpoints in Phase 3a Trial for Crohn Disease. HCPLive. October 12, 2023. Accessed May 31, 2024. https://www.hcplive.com/view/mirikizumab-achieves-primary-endpoints-in-phase-3a-trial-for-crohn-disease}
3. ^{Campbell, P. FDA Approves Mirikizumab (Omvoh) for Ulcerative Colitis. HCPLive. October 26, 2023. Accessed May 31, 2024. https://www.hcplive.com/view/fda-approves-mirikizumab-omvoh-for-ulcerative-colitis}