Omvoh (mirikizumab) / Eli Lilly - LARVOL DELTA

The Urgency Numeric Rating Scale: Psychometric Evaluation in Adults with Crohn's Disease. (PubMed, Adv Ther) - P3 | "The Urgency NRS demonstrated strong psychometric properties in the VIVID-1 population of moderately to severely active CD. Analyses also suggested meaningful improvement and remission thresholds."

Journal • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

Mirikizumab pharmacokinetics and exposure-response in pediatric patients with moderate-to-severe ulcerative colitis. (PubMed, CPT Pharmacometrics Syst Pharmacol) - P2 | "The E/R relationship for observed change from baseline in MMS at Week 12 is also similar to the adult model prediction. The PK modeling and E/R analyses suggested optimal doses of intravenous mirikizumab 300 mg for weight >40 kg, 5 mg/kg for weight ≤40 kg every 4 weeks (Q4W) during induction, and subcutaneous mirikizumab 200 mg (>40 kg), 100 mg (>20 to ≤40 kg), or 50 mg (≤20 kg) Q4W during maintenance therapy for pediatric patients with moderate-to-severe UC."

Journal • PK/PD data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Pediatrics • Ulcerative Colitis

Targeting mucosal healing in Crohn's disease: efficacy of novel pathways and therapeutic targets. (PubMed, Expert Opin Ther Targets) - "We compare these therapies with placebo for both induction and maintenance of remission, based on a PubMed literature review for published articles and ClinicalTrials.gov for ongoing trials. Upadacitinib and anti-IL23p19 agents (risankizumab, guselkumab and mirikizumab) are promising advanced non-TNF-targeting therapies for inducing endoscopic remission and mucosal healing but further studies are needed to integrate mucosal healing into a broader definition of endoscopic response, with a unified and precise definition."

Journal • Review • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • IL12A • IL23A • JAK1

Lilly's Omvoh (mirikizumab) recommended by CHMP for approval in the European Union for adults with moderately to severely active Crohn's disease (PRNewswire) - "Eli Lilly and Company (NYSE: LLY) announced today that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for Omvoh (mirikizumab), an interleukin-23p19 (IL-23p19) antagonist, for the treatment of adults with moderately to severely active Crohn's disease who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a biologic treatment....Lilly has submitted for Omvoh in Crohn's disease around the globe, including the U.S. and Japan. Decisions are expected from these regulatory authorities starting in the first half of 2025."

CHMP • EMA approval • FDA approval • Japan approval • Crohn's disease • Immunology • Inflammatory Bowel Disease

Comparative Effectiveness of Second-Line Biologic Therapies in Patients With Moderate to Severe Ulcerative Colitis: A Population-Based Cohort Study (ACG 2024) - "This study aims to evaluate the real-world efficacy of Janus kinase (JAK) inhibitors, specifically tofacitinib, upadacitinib, and filgotinib, in comparison with anti-integrin and interleukin (IL) antibodies (vedolizumab, ustekinumab, and mirikizumab) for the treatment of moderate to severe UC. A total of 2,547 JAK inhibitor users were propensity-score matched with anti-integrin and anti-IL monoclonal antibody users diagnosed with moderate to severe UC. Patients treated with JAK inhibitors exhibited a significantly reduced risk of emergency department visits (RR: 0.806; 95% CI: 0.724-0.897), megacolon (RR: 0.548; 95% CI: 0.384-0.781), diarrhea (RR: 0.717; 95% CI: 0.654-0.786), fatigue (RR: 0.765; 95% CI: 0.660-0.887), abdominal pain (RR: 0.765; 95% CI: 0.660-0.887), and anemia (RR: 0.835; 95% CI: 0.741-0.942) compared to those treated with vedolizumab, ustekinumab, and mirikizumab during an average of three years follow-up. No significant differences were observed in..."

Clinical • HEOR • Anemia • Colon Cancer • Colorectal Cancer • Fatigue • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Hematological Disorders • Immunology • Infectious Disease • Inflammatory Bowel Disease • Oncology • Pain • Septic Shock • Solid Tumor • Ulcerative Colitis

Effects of mirikizumab and ustekinumab on histologic inflammation evaluated by comprehensive assessment in 5 intestinal segments in a randomized controlled phase 3 trial of participants with Crohn's disease (KDDW 2024) - P3 | "All histology-based endpoints were achieved by MIRI versus PBO."

Clinical • P3 data • Crohn's disease • Gastroenterology • Immunology • Inflammation • Inflammatory Bowel Disease

Roche, Lilly face conditional reimbursement for MS and ulcerative colitis treatments (Korea Biomedical Review) - "Lilly Korea's ulcerative colitis treatments, including Omvoh Injection 20 mg/ml (mirikizumab), Omvoh Prefilled Pen Inj. 100 mg/ml, and Omvoh Prefilled Syringe Inj. 100 mg/ml, were reviewed. Roche Korea's multiple sclerosis treatment, Ocrevus (ocrelizumab), was given a conditional pass, sending the decision back to pharmaceutical companies."

Reimbursement • Immunology • Inflammatory Bowel Disease • Multiple Sclerosis • Ulcerative Colitis

Comparative Safety Profiles of Second Line Biologic Therapies in Patients With Moderate to Severe Ulcerative Colitis: A Nationwide Population-Based Cohort Study in the USA (ACG 2024) - "JAK inhibitor users (tofacitinib, upadacitinib, and filgotinib) were propensity score-matched to those receiving vedolizumab, ustekinumab, and mirikizumab, adjusting for baseline demographics, comorbidities, concomitant medications, and laboratory data. A total of 2,665 patients diagnosed with moderate to severe UC using JAK inhibitors and 18,136 patients using anti-integrin or anti-IL monoclonal antibodies were included in the study. After propensity score matching, patients receiving JAK inhibitors demonstrated a significantly higher risk of joint pain (RR = 0.74; 95% CI: 0.66-0.83), myalgia (RR = 0.73; 95% CI: 0.56-0.95), headache (RR = 0.60; 95% CI: 0.48-0.75), urinary tract infection (RR = 0.69; 95% CI: 0.54-0.88), and VTE (RR = 0.60; 95% CI: 0.45-0.81) compared to those treated with vedolizumab, ustekinumab, and mirikizumab. No significant differences were observed in MACE, malignancies, and opportunistic infections between the two groups."

Clinical • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Herpes Simplex • Herpes Zoster • Immunology • Infectious Disease • Inflammatory Arthritis • Inflammatory Bowel Disease • Musculoskeletal Diseases • Musculoskeletal Pain • Nephrology • Oncology • Pain • Rheumatoid Arthritis • Rheumatology • Ulcerative Colitis • Varicella Zoster • Venous Thromboembolism

Efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn's disease: a phase 3, multicentre, randomised, double-blind, placebo-controlled and active-controlled, treat-through study. (PubMed, Lancet) - P3 | "Mirikizumab was safe and effective as induction and maintenance treatment for patients with moderately-to-severely active Crohn's disease who had intolerance, inadequate response, or loss of response to standard therapy."

Journal • P3 data • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammatory Bowel Disease • Novel Coronavirus Disease • Ulcerative Colitis

Guselkumab Binding to CD64+ IL-23–Producing Myeloid Cells Enhances Potency for Neutralizing IL-23 Signaling (ACG 2024) - "Guselkumab (GUS), risankizumab (RZB), and mirikizumab (MIRI) are monoclonal antibodies that bind the IL-23p19 subunit. Analysis of RNA sequencing datasets showed FCGR1A , IL23A , and IL12B were significantly increased in inflamed versus non-inflamed IBD gut biopsies, and IL23A was predominantly expressed by FCGR1A -expressing myeloid cells. GUS, RZB, and MIRI displayed single-digit picomolar binding affinity for IL-23. GUS demonstrated binding to CD64, while no binding was observed for RZB or MIRI."

Gastroenterology • Gastrointestinal Disorder • Inflammatory Bowel Disease • FCGR1A • IL12B • IL23A

Comparative Efficacy and Safety of Subcutaneous Vedolizumab versus Other Targeted Inflammatory Bowel Disease Therapies in Patients With Moderate to Severe Ulcerative Colitis: A Network Meta-Analysis (ACG 2024) - "Phase 3, randomized controlled trials of targeted IBD therapies (adalimumab, etrasimod, golimumab, infliximab, mirikizumab, ozanimod, tofacitinib, upadacitinib, ustekinumab and vedolizumab) in adults with moderate to severe UC were included. Of the 29 studies, 10 were newly included in this update. The odds of achieving clinical response or clinical remission with vedolizumab SC were either higher or not significantly different to other targeted IBD therapies ( Figure 1 ). For most safety outcomes, except serious infections, vedolizumab SC had a similar or favorable profile compared with other targeted IBD therapies; there were no significant differences between vedolizumab SC and vedolizumab IV ( Table 1 )."

Retrospective data • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Oncology • Ulcerative Colitis

MIRROR: Mirikizumab Real World Protocol (clinicaltrials.gov) - P=N/A | N=100 | Not yet recruiting | Sponsor: University of North Carolina, Chapel Hill

New trial • Real-world • Real-world evidence • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

“Extension application to add a new strength of 200 mg grouped…moderately to severely active Crohn's disease who have had an inadequate response with…based mainly on final results from study I6T-MC-AMAM…as a consequence, sections 1, 2, 4.1, 4.2, 4.4, 4.5, 4.8, 5.1, 5.2, 5.3, 6.1, 6.5, 6.6 and 8 of the SmPC are updated” (European Medicines Agency) - Pharmacovigilance Risk Assessment Committee (PRAC)-Draft agenda for the meeting on 25 – 28 Nov 2024: “For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP”

PRAC • Crohn's disease • Immunology • Inflammatory Bowel Disease

AGA Living Clinical Practice Guideline on Pharmacological Management of Moderate-to-Severe Ulcerative Colitis. (PubMed, Gastroenterology) - "This guideline provides a comprehensive, patient-centered approach to the pharmacological management of patients with moderate-to-severe UC."

Clinical guideline • Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Oncology • Ulcerative Colitis

Mirikizumab achieved comprehensive disease control in patients with ulcerative colitis from phase 3 LUCENT-1 and LUCENT-2 trials (KDDW 2024) - "Miri demonstrated substantial impact on CDC by achieving holistic combined endpoints including disease activity, bowel urgency, and IBDQ."

Clinical • P3 data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Efficacy and Safety of Biological Therapy for Treating Adults With Moderate-Severe Crohn's Disease: A Systematic Review and Network Meta-Analysis (ISPOR-EU 2024) - "However, 30-45% cases are resistant to first-line treatments, thus requiring the use of add-on biologics (e.g., infliximab, adalimumab, certolizumab, vedolizumab, ustekinumab)...Alongside infliximab 5mg/kg (p-score probabilities of 95%) and 10mg/kg (85%), recently approved drugs such as mirikizumab 600mg (90%), guselkumab 200mg (87%) and 600mg (86%) presented higher probabilities of disease remission... Moderate-to-high quality evidence highlight new inhibitors of interleukin-23 as more promising alternatives for the treatment of Crohn's disease. Given their safety profile, some anti-TNF drugs should be avoided in clinical practice. Other important factors, such as drugs’ access and costs, should be considered for this decision."

Retrospective data • Review • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

Interleukin-12/23 vs Interleukin-23 Inhibitors in Moderate to Severe Crohn's Disease: A Systematic Review and Network Meta-Analysis (ACG 2024) - "Data from 12 RCTs (6,577 patients) were included in the final analysis. There were no significant differences between Ustekinumab and IL-23 inhibitors (Risankizumab, Mirkiziumab and Guselkumab) in terms of the clinical and endoscopic outcomes in the induction and maintenance phases. Ustekinumab 6 mg/kg induction dose was associated with a significantly higher rate of serious adverse events (SAE) compared to Risankizumab 600 mg every four weeks [Risk ratio (RR): 2.02, 95% Confidence interval (95% CI): 1.28 - 3.19] and 1200 mg every four weeks (RR: 3.09 95% CI: 1.82-5.25) induction doses."

Retrospective data • Review • Crohn's disease • Dermatology • Gastroenterology • Immunology • Inflammatory Bowel Disease • Psoriasis • IL12A • IL23A

Efficacy and Safety of Interleukin-12, 23 Inhibitors vs Interleukin-23 inhibitors for Moderate to Severe Ulcerative Colitis: A Systematic Review and Network Meta-Analysis (ACG 2024) - "Seven studies (4,361 patients) were analyzed. Mean age of the patients was 42.1 years [Standard deviation : 13.9] and 40% of them were women. Ustekinumab 6 mg/kg demonstrated superior efficacy compared to Mirikizumab 300 mg in terms of clinical response (Risk ratio [RR]: 1.32; 95% confidence intervals [95% CI]: 1.04, 1.66) (Figure 1A)."

Retrospective data • Review • Dermatology • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Psoriasis • Ulcerative Colitis • IL12A • IL23A

Mirikizumab for Chronic Plaque Psoriasis: A Systematic Review and Meta-Analysis. (PubMed, Am J Ther) - No abstract available

Journal • Retrospective data • Review • Dermatology • Immunology • Psoriasis

Head-to-Head Comparison of Biologics vs Ustekinumab for Crohn's Disease: A Systematic Review of Efficacy (ACG 2024) - "A total of four phase - 3 trials comparing various biologics with Ustekinumab were included this study - SEAVUE (Adalimumab), SEQUENCE (Risankizumab), VIVID-1(Mirikizumab) and GALAXI 2 and 3 (Guselkumab). The endpoints reviewed include - Clinical remission, Endoscopic remission and Endoscopic response. In terms of Clinical remission, Mirikizumab (54.10% vs 48.40%, p 0.113) and Guselkumab (70.30% vs 62.90%, p 0.058) were more effective than Ustekinumab."

Clinical • Head-to-Head • Review • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • IL12A

The Role of Mirikizumab in Treating Ulcerative Colitis Assessing Effectiveness, Patient Responses and Adverse Events: A Systematic Review and Meta-analysis (IASGO 2024) - No abstract available

Adverse events • Retrospective data • Review • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Mirikizumab Pharmacokinetics and Exposure-Response Relationships in Patients With Moderately to Severely Active Crohn's Disease in Phase 2 and 3 Studies (ACG 2024) - "MIRI PK was best described by a linear two-compartment model with first-order absorption. Population (PopPK) model-estimated parameters were consistent across both trials (Table) . AMAG indicated a near-maximal efficacy for doses between 600 and 1000 mg IV for endoscopic response by SES-CD at W12, suggesting that 900 mg IV in VIVID-1 would produce near-maximal effect for W12 endpoints ."

Clinical • P2 data • PK/PD data • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Efficacy and Safety of Long-Term Mirikizumab Treatment in Patients With Moderate to Severe Crohn's Disease (ACG 2024) - P2, P3 | "Rates of TEAEs of special interest were as follows: any infection/infestation, 54.7% (n=58); opportunistic infections, 3.8% (n=4; 1 candidiasis; 3 herpes zoster [with concomitant azathioprine use in 2 of these cases]); malignancies, 0.9% (n=1 non-melanoma skin cancer [basal cell carcinoma]); and cerebro-cardiovascular events, 0.9% (n=1 bradycardia). 106 patients enrolled in AMAX; at database lock, median miri treatment duration (Q1, Q3) was 5.6 (5.3, 5.9) years. At Week 156 of AMAX, 18 patients (17.0%) had discontinued. For endoscopic results, 17 patients (16.0%) did not yet have data available for week 156."

Clinical • Basal Cell Carcinoma • Candidiasis • Cardiovascular • Crohn's disease • Gastroenterology • Genetic Disorders • Herpes Zoster • Immunology • Infectious Disease • Inflammatory Bowel Disease • Non-melanoma Skin Cancer • Skin Cancer • Solid Tumor • Varicella Zoster

Exit Interviews Exploring Patients' Experience of Changes in Their Fatigue During the Phase 3 Clinical Trial of Mirikizumab for Treatment of Moderately to Severely Active Crohn's Disease (ACG 2024) - "A sub-set of participants from either mirikizumab, ustekinumab or placebo arms were asked open-ended questions to explore changes in fatigue. Among the 31 participants who were interviewed (61.3% male [n=19], 90.3% White [n=28]), median age was 42 (n=30; range: 24–75) years, median CD duration was 5.9 (n=30; range: 1.4–54.3) years, 31.0% (n=9/29) had a college degree or higher and 41.4% (n=12/29) were employed full-time. Participants were from the United States (n=15), Czech Republic (n=5), Germany (n=5), Poland (n=3), Australia (n=2) and Canada (n=1). At the start of the trial, participants reported varied impact of fatigue in their daily life (table)."

Clinical • Interview • P3 data • Crohn's disease • Fatigue • Gastroenterology • Immunology • Inflammatory Bowel Disease

Effects of Mirikizumab versus Placebo on Histologic Inflammation Evaluated by Comprehensive Assessment in 5 Intestinal Segments in a Randomized, Controlled Phase 3 Trial of Participants With Crohn's Disease (ACG 2024) - "At W12: treatment with MIRI resulted in nominally statistically significantly higher rates of H-Res in all three patient groups, differences between MIRI vs PBO were nominally significant in achieving H-Rem in all patients and in non-BF and BF patients. For W52: composite H-Res differences between MIRI vs PBO were nominally statistically significant in all patient groups, composite H-Rem differences were nominally statistically significant between MIRI vs PBO in all patients, in non-BF patients, and in BF patients (Table). MIRI achieved nominally significantly higher rates of H-Res and H-Rem compared to PBO in all patients at W12 and W52."

Clinical • P3 data • Crohn's disease • Gastroenterology • Immunology • Inflammation • Inflammatory Bowel Disease • Pain