Lilly's First-in-Class IL-23p19 Inhibitor Mirikizumab Demonstrates Significant Efficacy in Phase 3 Trial for Ulcerative Colitis

Inflammatory Bowel Disease (UC, CD, Image Source: tahminahaqmd.com)

News on February 19, 2022 /BioValleyBIOON/ --Eli Lilly(Eli Lilly) recently announced the data from the Phase 3 clinical program of the novel anti-inflammatory drug mirikizumab for the treatment of moderate to severe ulcerative colitis (UC) for the first time at the 17th European Crohn's and Colitis Organisation (ECCO) Congress in 2022. The data come from the pivotal Phase 3 LUCENT-1 study (NCT03518086), a 12-week placebo-controlled induction Phase 3 study.Conducted in patients with moderate to severe UC who have failed conventional and/or biologic therapies and/or JAK inhibitors., evaluated the efficacy and safety of mirikizumab.

The results published at the meeting showed that, regarding the primary endpoint: at week 12 of treatment,Compared with the placebo group, the clinical remission rate in the mirikizumab treatment group was statistically higher (p=0.00006).When the inflammation of the colon is controlled or alleviated, leading to normalization or near-normalization of symptoms such as frequency of bowel movements and bleeding, clinical remission can be achieved. Additionally,The study also met all key secondary endpoints: compared with the placebo group, the mirikizumab treatment group achieved statistically significant improvements in clinical, symptomatic, endoscopic, and histological (tissue cell level) indicators., including defecation urgency, clinical response, endoscopic remission, symptom relief, and improvement in endoscopic histological inflammation, with highly statistically significant p-values. In addition,Mirikizumab Showed Rapid Improvement in Patient Symptoms Just 4 Weeks After Starting TreatmentMirikizumab can also alleviate symptoms in patients who previously had no response or stopped responding to biological and/or Janus kinase (JAK) inhibitor treatments.

UC is a chronic inflammatory disease of the large intestine (also known as the colon), which affects the lining of the colon and can lead to the formation of small sores or ulcers. This inflammation can cause abdominal pain, frequent and urgent bowel movements, bloody stools, and incontinence. UC can result in severe and debilitating disruptions in daily life. Globally, millions of people suffer from UC.

Mirikizumab is a humanized IgG4 monoclonal antibody that targets and binds to the p19 subunit of IL-23. This drug is currently being developed for various immune-mediated diseases, including plaque psoriasis (PsO), ulcerative colitis (UC), and Crohn's disease (CD). UC and CD are two types of inflammatory bowel disease that can cause severe and debilitating symptoms, interfering with daily life.

The Phase 3 clinical program LUCENT for mirikizumab in the treatment of UC includes three studies: LUCENT-1, LUCENT-2 (NCT03524092), and LUCENT-3 (NCT03519945). LUCENT-2 is a multicenter, randomized, double-blind, placebo-controlled maintenance study enrolling patients who completed the 12-week treatment period in the LUCENT-1 induction study. The final study involves participants who were previously treated with mirikizumab for UC.Clinical Trialin patients.

There is still a need for additional treatment options to relieve UC patients of their most challenging symptoms. According to data from the LUCENT program,Eli LillyIt is planned that in the first half of 2022, the submission will first be made to the U.S. Food and Drug Administration (FDA) submitted the marketing application for mirikizumab in the treatment of UC, followed by submissions to other regulatory agencies worldwide. Mirikizumab has the potential to become the first anti-IL-23p19 biologic for the treatment of UC.

The LUCENT-1 study enrolled a total of 1,162 patients, including those who had not previously received biologic treatment (biologic-naive) and those who had previously received one biologic treatment but experienced treatment failure (biologic-experienced).

The results showed that: (1) At week 12 of treatment, 24.2% (n=210/868) of patients in the mirikizumab group and 13.3% (n=39/294) in the placebo group achieved clinical remission (p=0.00006), indicating improvement in symptom relief and elimination or near-elimination of inflammation. (2) At week 12 of treatment, 63.5% (n=551/868) of patients in the mirikizumab group and 42.2% (n=124/294) in the placebo group achieved clinical response (p<0.00001).

At week 12 of treatment, 45.5% (n=395/868) of patients in the mirikizumab group and 27.9% (n=82/294) in the placebo group achieved symptom relief (p<0.001). As early as within 4 weeks of treatment, 21.8% (n=189/868) of patients in the mirikizumab group and 12.9% (n=38/294) in the placebo group experienced rapid symptom improvement (p<0.001).

As early as within 2 weeks of treatment and continuing to week 12, patients in the mirikizumab treatment group experienced a statistically significant reduction in the 11-point intestinal urgency severity score. At week 12, the average score for patients in the mirikizumab treatment group decreased by 2.59 points (2.32 to 2.85), while the average score for the placebo group decreased by 1.63 points (1.18 to 2.09) (p<0.00001). The 2-week intestinal urgency endpoint was pre-specified but not multiplicity-controlled.

In the study, the overall safety profile of mirikizumab was consistent with previous studies in UC and aligned with other anti-IL-23p19 antibodies in other therapeutic areas. Compared to the placebo group, the incidence of serious adverse events reported in the mirikizumab treatment group was lower (mirikizumab: 2.8%, n=27; placebo: 5.3%, n=17), and the likelihood of discontinuing the study due to adverse events was also lower (mirikizumab: 1.6%, n=15; placebo: 7.2%, n=23). (Bioon.com)

Source of Original Text:Nearly Two-Thirds of Patients Respond to Mirikizumab Treatment at 12 Weeks in Lilly's First-in-Class Ulcerative Colitis Phase 3 LUCENT-1 Study