Dr. Lotus Mallbris Discusses Positive Results from the VIVID-1 P-III Study of Mirikizumab for the Treatment of Crohn's Disease in Adults

Shots:

Dr. Lotus Mallbris shares the positive endpoint results of the VIVID-1 P-III study, evaluating the safety and efficacy of mirikizumab for the treatment of adults with moderately to severely active Crohn’s disease
While shedding light on the mechanism of mirkizumab, Lotus highlights that available therapies to treat Crohn’s disease often fail to achieve clinical remission for many patients
Lotus discusses briefly the VIVID-2 P-III study to evaluate the long-term efficacy and safety of mirikizumab in adults with moderately to severely active Crohn’s disease

Saurabh: VIVID-1 has successfully met all its endpoints, i.e., co-primary and secondary, so give us an overview of these endpoints and whether were there any challenges faced during this study.

Lotus: In the Phase 3 study, mirikizumab met the co-primary and all major secondary endpoints compared to placebo. 
The study’s co-primary endpoints, which included the 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, as well as the proportion of participants achieving clinical response by PRO at Week 12 and endoscopic response (defined as ≥50% reduction from baseline in Simple Endoscopic Score – Crohn's Disease [SES-CD] Total Score) at Week 52 compared to placebo.

In addition to meeting the above co-primary endpoints, mirikizumab achieved all individual and composite major secondary endpoints at Week 52 compared to placebo (p<0.000001). Notably, of the patients who received mirikizumab, 54.1% achieved clinical remission at Week 52 compared to 19.6% of patients who received placebo (p<0.000001). For the endpoint of clinical remission (defined as CDAI <150), mirikizumab demonstrated non-inferiority versus ustekinumab (non-inferiority margin of 10%).  Although the results for mirikizumab in endoscopic response (≥50% reduction from baseline in SES-CD Total Score) at Week 52 were numerically higher, particularly in the non-multiplicity-controlled bio-failed population, it did not reach superiority versus ustekinumab.

Saurabh: Crohn’s Disease has now become a global issue, and many people are now suffering from it. There are many products on the market regarding the above, so what is different with mirikizumab (an investigational interleukin-23p19 antagonist)?

Lotus: Mirikizumab works by selectively targeting the p19 subunit of IL-23, which plays a role in inflammation related to inflammatory bowel diseases. Many people are seeking relief from their uncontrolled Crohn’s disease, including those still experiencing symptoms despite available therapies such as TNF inhibitors. Current therapies to treat Crohn’s disease often fail to achieve clinical remission for many of these patients, and of the patients who do achieve clinical remission, a substantial proportion lose it within the first year.

Helping patients achieve long-term clinical remission is what inspires us to develop innovative treatments for those with inflammatory bowel diseases.

Saurabh: Can you tell us about the safety profile of mirikizumab?

Lotus: The overall safety profile was consistent with the known safety profile for mirikizumab and consistent with the anti-IL-23p19 antibody class. 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 reported among patients treated with mirikizumab included infections, injection-site reactions, hypersensitivity, liver enzyme elevations, depression and suicidal thoughts. No major adverse cardiac events were observed in the mirikizumab arm.

Saurabh: What was the problem faced by the company during the early stage of the development of mirikizumab?

Lotus: An estimated 900,000 patients in the U.S. and 1 million patients in Europe currently suffer from Crohn’s disease, and 70% of those have moderate to severe disease. Although the majority of patients start on conventional therapy, such as corticosteroids and immunomodulators, many will unfortunately progress to having moderate to severe disease. 

There is a high unmet need for new medications for healthcare providers and people living with IBD to find treatment options that can effectively address the disease’s challenging symptoms, as current therapies to treat Crohn’s disease often fail to achieve remission for a majority of patients, and of the patients who do achieve remission, a substantial proportion lose it within the first year.

Saurabh: Now that the company is planning to submit a market application to the FDA, what is the commercialization strategy regarding the same?

Lotus: Lilly plans to submit a marketing application for mirikizumab in Crohn's disease in the U.S., followed by submissions to other regulatory agencies around the world in 2024.

Saurabh: Can we talk more about the VIVID program, trials, indications and what is the timeline of these clinical trials within this program?

Lotus: The VIVID program consists of VIVID-1 and VIVID-2 in adult patients with Crohn’s disease. VIVID-1 is a Phase 3 study evaluating the safety and efficacy of mirikizumab for the treatment of adults with moderately to severely active Crohn’s disease. The double-blind, treat-through design trial included mirikizumab, placebo and active control (ustekinumab) arms. VIVID-2 is a Phase 3 open-label, long-term extension study to evaluate the long-term efficacy and safety of mirikizumab in adults with moderately to severely active Crohn’s disease. Full data from the Phase 3 VIVID program will be disclosed in publications and at upcoming congresses. 

We are pleased with the results of the VIVID-1 study, which demonstrated that mirikizumab has the potential to help people with Crohn’s disease achieve clinical remission. These data are a part of a comprehensive submission package to regulatory authorities, which will take place in 2024.

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About the Author:

Dr. Lotus Mallbris

Dr. Lotus Mallbris is the senior vice president of global immunology development and medical affairs at Eli Lilly and Company. As head of immunology, she is working to improve the lives of millions with autoimmune diseases by furthering innovation in health care and solving problems for patients.

Dr. Mallbris joined Lilly in 2015 and leads the company’s multifunctional Global Clinical Development and Global Medical Affairs teams across the dermatology, rheumatology, and gastroenterology fields. Before joining Lilly, she spent several years at Pfizer and held leadership positions within the dermatology business. Prior to joining the corporate world, Dr. Mallbris was a practicing physician for more than 10 years, starting her career as a surgeon before transitioning to the field of dermatology.