A Comprehensive Monograph on Mirikizumab (Omvoh) for the Treatment of Inflammatory Bowel Disease

Executive Summary & Drug Profile

Executive Summary

Mirikizumab, marketed under the brand name Omvoh, represents a significant advancement in the therapeutic landscape for inflammatory bowel disease (IBD). It is a first-in-class, humanized immunoglobulin G4 (IgG4) monoclonal antibody that exhibits high specificity for the p19 subunit of the pro-inflammatory cytokine interleukin-23 (IL-23).[1] This targeted mechanism of action allows for selective inhibition of the IL-23 signaling pathway, a critical driver of mucosal inflammation in IBD.[3] Mirikizumab is approved for the treatment of adults with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD), offering a new therapeutic option for patients who have had an inadequate response to, lost response to, or were intolerant of conventional or other biologic therapies.[1]

The approvals were based on robust data from two pivotal Phase 3 clinical trial programs: LUCENT for ulcerative colitis and VIVID for Crohn's disease.[7] In UC, the LUCENT program demonstrated that Mirikizumab was superior to placebo for both inducing and maintaining clinical remission and endoscopic improvement.[6] Notably, the program was the first to formally establish efficacy in improving bowel urgency, a highly burdensome patient-reported symptom.[9] In CD, the VIVID-1 trial showed Mirikizumab was superior to placebo in achieving co-primary endpoints of clinical remission and endoscopic response at one year.[8] Long-term extension studies for both indications have confirmed the durability of these responses over multiple years, supported by a consistent and manageable safety profile.[11]

Developed by Eli Lilly and Company, Mirikizumab has secured regulatory approval from major global agencies, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).[6] Its unique mechanism, demonstrated efficacy on both clinical and patient-centric endpoints, and favorable long-term data position it as a key therapy in the evolving IBD treatment paradigm.

Drug Profile Summary

The following table provides a consolidated summary of key identifiers and characteristics for Mirikizumab. The use of multiple names and codes during its development and commercialization, such as the research code LY3074828 and the USAN-designated suffix "-mrkz," is common for biologic therapies. This table serves as a foundational reference.

Identifier/Characteristic	Details	Source(s)
International Nonproprietary Name (INN)	Mirikizumab	7
US Adopted Name (USAN)	Mirikizumab-mrkz	13
Brand Name	Omvoh	1
Developer/Manufacturer	Eli Lilly and Company	1
Research Code	LY3074828	7
DrugBank ID	DB14910	7
CAS Number	1884201-71-1	16
Drug Type	Biotech, Humanized (from mouse) IgG4 Monoclonal Antibody	1
Drug Class	Interleukin Inhibitor, IL-23 Antagonist, Immunomodulatory Agent	1
ATC Code	L04AC24	7
Chemical Formula	C6380​H9842​N1686​O2004​S48​	7
Molecular Weight	Approximately 143.77 kDa	7

The IL-23 Pathway in IBD and Mirikizumab's Targeted Mechanism of Action

Pathophysiological Role of the IL-23/Th17 Axis in IBD

The pathogenesis of inflammatory bowel disease is driven by a dysregulated immune response to intestinal antigens in genetically susceptible individuals. Central to this process is the interleukin-23/T helper 17 (IL-23/Th17) axis, which has been identified as a dominant regulatory pathway in both innate and adaptive immunity and a critical contributor to chronic mucosal inflammation.[3]

IL-23 is a heterodimeric cytokine composed of two subunits: a p40 subunit, which it shares with the cytokine IL-12, and a p19 subunit, which is unique to IL-23.[3] The primary role of IL-23 is to promote the differentiation, expansion, and functional maintenance of pathogenic T cell populations, most notably Th17 cells.[19] Upon activation by IL-23, these cells produce a potent cocktail of pro-inflammatory cytokines, including IL-17A, IL-17F, and IL-22.[19] This cytokine cascade perpetuates a cycle of inflammation, leading to the recruitment of other immune cells, disruption of the intestinal epithelial barrier, and the tissue damage characteristic of ulcerative colitis and Crohn's disease. The central role of this pathway has made it a highly attractive target for therapeutic intervention in IBD and other immune-mediated inflammatory diseases.[3]

Molecular Profile and Selective Inhibition of IL-23p19

Mirikizumab is a humanized immunoglobulin G4 (IgG4) monoclonal antibody specifically engineered to neutralize the biological activity of IL-23.[1] Its mechanism of action is predicated on high-affinity and high-specificity binding to the p19 subunit of the IL-23 cytokine.[3] This binding interaction is highly potent, with dissociation constants (

Kd​) measured at 21 pM for human IL-23 and 55 pM for cynomolgus monkey IL-23.[23]

By binding to the unique p19 subunit, Mirikizumab sterically obstructs the IL-23 cytokine from engaging with its cell surface receptor complex (IL-23R).[3] This blockade effectively abrogates the downstream intracellular signaling cascade, which is mediated through the Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway, involving primarily JAK2, TYK2, STAT3, and STAT4.[19] The interruption of this signal prevents the activation, proliferation, and stabilization of pathogenic Th17 cells and other IL-23-responsive immune cells, thereby reducing the production of downstream effector cytokines and ameliorating intestinal inflammation.[19]

The decision to target the p19 subunit represents a strategic refinement in biologic therapy for IBD. Earlier therapies, such as ustekinumab, target the p40 subunit, which is common to both IL-12 and IL-23.[3] Consequently, p40 inhibition blocks the activity of both cytokine pathways. While effective, this dual blockade also affects the IL-12/Th1 pathway, which plays a distinct role in host defense against certain pathogens. By selectively targeting the p19 subunit, Mirikizumab's activity is confined to the IL-23 pathway, leaving the IL-12 pathway intact.[3] This targeted approach is designed to maximize therapeutic efficacy against the key pathogenic driver of IBD while minimizing broader immunosuppressive effects, potentially leading to an improved benefit-risk profile.

Further underscoring its sophisticated design, Mirikizumab is an engineered IgG4κ monoclonal antibody incorporating several key mutations to optimize its stability and safety.[15] These include:

• S228P: A mutation in the hinge region that prevents "Fab-arm exchange," a phenomenon common to native IgG4 antibodies that can lead to the formation of bispecific antibodies and reduce therapeutic potency. This modification stabilizes the molecule into a conventional, monospecific antibody structure.
• F234A and L235A: These mutations in the Fc region are designed to abrogate effector functions by eliminating binding to Fc gamma receptors (FcγR). This ensures that the antibody acts as a pure neutralizing agent, blocking its target without recruiting other immune cells or triggering antibody-dependent cell-mediated cytotoxicity (ADCC).
• K447>del: A deletion at the C-terminus to reduce structural heterogeneity.

This level of precision protein engineering ensures that the therapeutic effect of Mirikizumab is derived solely from the specific neutralization of IL-23, without confounding effects from the antibody backbone itself. This approach is a hallmark of next-generation biologic therapies, designed for maximal target specificity and safety.

Clinical Efficacy in Moderately to Severely Active Ulcerative Colitis

The LUCENT Phase 3 Program Overview

The clinical efficacy and safety of Mirikizumab for the treatment of ulcerative colitis were definitively established in the LUCENT Phase 3 program. This comprehensive program consisted of two pivotal, randomized, double-blind, placebo-controlled trials: LUCENT-1, a 12-week induction study, and LUCENT-2, a 40-week maintenance study for patients who responded to induction therapy.[6] The program was followed by LUCENT-3, a long-term, open-label extension study to assess durability and safety over several years.[2] The trials enrolled adult patients with moderately to severely active UC who had previously failed or were intolerant to conventional therapies (e.g., corticosteroids, immunomodulators) or biologic treatments.[7]

Induction of Remission (LUCENT-1)

The LUCENT-1 trial was designed to evaluate the efficacy of Mirikizumab in inducing clinical remission in 1,281 patients. Participants were randomized in a 3:1 ratio to receive Mirikizumab 300 mg administered intravenously (IV) or placebo every four weeks for 12 weeks.[9]

The study successfully met its primary endpoint, demonstrating a statistically significant and clinically meaningful benefit for Mirikizumab. At week 12, 24.2% of patients in the Mirikizumab group achieved clinical remission, compared to 13.3% in the placebo group (p<0.001).[6]

Mirikizumab also demonstrated superiority across all major secondary endpoints, underscoring its broad efficacy during the induction phase. Key secondary outcomes at week 12 included [6]:

• Clinical Response: 65% of Mirikizumab-treated patients achieved clinical response, versus 43% of placebo-treated patients.
• Endoscopic Remission: 36% of patients in the Mirikizumab arm achieved endoscopic remission, compared to 21% in the placebo arm (p<0.001).
• Histologic-Endoscopic Mucosal Improvement: 27% of patients receiving Mirikizumab achieved this composite endpoint of deep healing, versus 14% for placebo (p<0.001).

A particularly noteworthy aspect of the LUCENT program was its pioneering assessment of bowel urgency. This symptom, defined as the sudden or immediate need for a bowel movement, is frequently cited by patients as one of the most debilitating and socially disruptive aspects of UC. The LUCENT trials were the first to incorporate a validated, patient-reported Urgency Numeric Rating Scale and formally evaluate it as an endpoint.[9] Mirikizumab demonstrated a significant improvement in bowel urgency compared to placebo, addressing a critical unmet need and marking a shift in IBD clinical trial design toward more patient-centric outcomes.[28]

Maintenance of Remission (LUCENT-2)

Patients who achieved a clinical response to Mirikizumab at the end of the 12-week LUCENT-1 induction study were eligible for enrollment in the LUCENT-2 maintenance trial. In this study, 544 patients were re-randomized in a 2:1 ratio to receive either Mirikizumab 200 mg administered subcutaneously (SC) or placebo every four weeks for an additional 40 weeks, for a total of 52 weeks of continuous treatment.[9]

The primary endpoint of the maintenance phase was clinical remission at week 52. Mirikizumab was significantly superior to placebo in maintaining remission, with 49.9% of patients in the Mirikizumab group achieving this endpoint compared to 25.1% in the placebo group (p<0.001).[9] This result confirms the ability of Mirikizumab to sustain the benefits achieved during induction over the long term. The superiority of Mirikizumab was consistent across key secondary endpoints, including sustained endoscopic remission, histologic improvement, and continued relief from bowel urgency through the 52-week treatment period.[9]

Long-Term Efficacy and Durability (LUCENT-3)

The LUCENT-3 open-label extension study provided crucial data on the long-term durability of Mirikizumab's effect, following patients for up to three years.[11] The results demonstrated high rates of sustained efficacy among patients who were in clinical remission after one year of treatment. Analysis of this cohort after an additional two years of continuous therapy (three years total) revealed remarkable durability of response [11]:

• 81% of patients maintained long-term clinical remission.
• 82% of patients maintained long-term endoscopic remission.
• 72% of patients achieved mucosal healing.
• 79% of patients maintained corticosteroid-free clinical remission.

These sustained, deep responses were observed regardless of patients' prior treatment history, including those who had previously failed TNF inhibitors or other advanced therapies, highlighting Mirikizumab's robust efficacy in a difficult-to-treat population.[11]

Clinical Efficacy in Moderately to Severely Active Crohn's Disease

The VIVID Phase 3 Program Overview

The efficacy of Mirikizumab in Crohn's disease was established through the VIVID Phase 3 program, with VIVID-1 serving as the pivotal 52-week induction and maintenance trial.[8] This study featured a robust design that included both a placebo arm and an active-control arm with ustekinumab, allowing for both regulatory assessment and comparative evaluation.[33] The program also includes the VIVID-2 long-term extension study, which follows patients to assess durability of response and long-term safety.[8] The VIVID-1 trial enrolled adults with moderately to severely active CD who had an inadequate response, loss of response, or intolerance to conventional and/or biologic therapies.[8]

Induction and Maintenance Efficacy (VIVID-1)

VIVID-1 was a randomized, double-blind, treat-through study, a design in which patients remain on their assigned treatment for the full 52-week duration, which more closely reflects real-world clinical practice compared to traditional re-randomization designs.[34] The study successfully achieved its co-primary endpoints at week 52, demonstrating the superiority of Mirikizumab over placebo [8]:

• Clinical Remission by Crohn's Disease Activity Index (CDAI): At one year, 53% of patients treated with Mirikizumab achieved clinical remission, compared to 36% in the placebo group (p<0.001).
• Endoscopic Response: At one year, 46% of patients treated with Mirikizumab achieved endoscopic response (visible healing of the intestinal lining), compared to 23% in the placebo group (p<0.001).

These comparisons to placebo are particularly conservative and underscore the potency of Mirikizumab. A significant portion of patients in the placebo arm (40%) who were not responding at 12 weeks were switched to open-label Mirikizumab, yet the primary analysis still showed a highly significant benefit for the group initially randomized to Mirikizumab.[6] Furthermore, Mirikizumab was superior to placebo on all key major secondary endpoints (

p<0.000001).[8]

Comparative Efficacy vs. Ustekinumab (VIVID-1)

The inclusion of an active comparator arm with ustekinumab in VIVID-1 provides valuable data for clinical positioning. The results of this head-to-head comparison are nuanced and reveal important distinctions between the two therapies.

• Clinical Remission: Mirikizumab demonstrated non-inferiority to ustekinumab in achieving CDAI clinical remission at week 52 (p=0.113), indicating a comparable effect on symptom control.[8] However, it did not demonstrate superiority.
• Endoscopic Response: Mirikizumab did not meet the pre-specified endpoint for non-inferiority compared to ustekinumab for endoscopic response (p=0.51).[8] This suggests that, based on macroscopic endoscopic assessment, ustekinumab may have an edge in achieving mucosal healing at one year.

This split verdict—comparable symptom control but not comparable endoscopic healing—presents a complex clinical picture. It suggests that for patients where the primary goal is symptomatic relief, Mirikizumab is a valid alternative to ustekinumab. However, if achieving the highest degree of visible mucosal healing is the priority, the data from VIVID-1 does not support Mirikizumab as being equivalent to ustekinumab.

However, a deeper analysis of tissue-level healing revealed a different and compelling story. Despite the endoscopic findings, post-hoc analyses showed that Mirikizumab was superior to ustekinumab in achieving histologic response at week 52 (58.2% vs. 48.8%; p=0.0075).[35] This superiority was also observed in the difficult-to-treat subgroup of patients with prior biologic failure.[35] This finding suggests that Mirikizumab may promote a more profound level of healing at the cellular and microscopic level, which may not be fully captured by standard endoscopic scoring. This aligns with the evolving treatment goals in IBD, as advocated by organizations like the European Crohn's and Colitis Organisation (ECCO), which are moving toward histologic remission as a more ambitious target associated with better long-term outcomes.[36] This positions Mirikizumab as a therapy that may be uniquely effective at resolving the fundamental cellular inflammation that drives long-term bowel damage.

Long-Term Efficacy and Durability (VIVID-2)

The VIVID-2 open-label extension study is providing data on the long-term maintenance of response in patients with CD. The results indicate strong durability. Among patients who achieved both clinical remission and endoscopic response after one year in VIVID-1, nearly 90% maintained clinical remission after an additional year of treatment (two years total).[8] Similarly, among those who achieved an endoscopic response at one year, over 80% maintained that response after a second year of treatment.[8] These data support the role of Mirikizumab in providing stable, long-term disease control in Crohn's disease.

The following table summarizes the key primary efficacy outcomes from the pivotal Phase 3 trials that supported the regulatory approvals of Mirikizumab for both UC and CD.

Indication	Trial	Endpoint	Mirikizumab Arm (%)	Placebo Arm (%)	p-value	Source(s)
Ulcerative Colitis	LUCENT-1 (Induction)	Clinical Remission @ Week 12	24.2	13.3	<0.001	6
Ulcerative Colitis	LUCENT-2 (Maintenance)	Clinical Remission @ Week 52	49.9	25.1	<0.001	9
Crohn's Disease	VIVID-1	CDAI Clinical Remission @ Week 52	53	36*	<0.001	10
Crohn's Disease	VIVID-1	Endoscopic Response @ Week 52	46	23*	<0.001	10
*Placebo arm included patients who switched to Mirikizumab at Week 12 if non-responsive.

Comprehensive Safety, Tolerability, and Risk Management Profile

Overall Safety Profile

The safety of Mirikizumab has been extensively evaluated across its clinical development programs for both ulcerative colitis and Crohn's disease. The overall safety profile is consistent and manageable, aligning with the known risks of other biologic therapies that modulate the IL-23 pathway.[8] In the pivotal LUCENT trials for UC, the frequency of treatment-emergent adverse events (TEAEs) was similar between the Mirikizumab and placebo groups. Notably, there were numerically fewer serious adverse events (SAEs) and discontinuations due to adverse events in patients receiving Mirikizumab compared to placebo during the induction phase.[26] Long-term extension studies have not identified any new safety signals, confirming its suitability for chronic administration.[11]

Common Adverse Reactions

The most frequently reported adverse reactions are generally mild to moderate in severity. The profile is slightly different between the two approved indications.

• In Ulcerative Colitis:
• Induction Phase: The most common adverse reactions were upper respiratory tract infections (URTIs), including nasopharyngitis (8% with Mirikizumab vs. 6% with placebo) and arthralgia (joint pain) (2% vs. 1%).[6]
• Maintenance Phase: Common reactions included URTIs (14% vs. 12%), injection site reactions, arthralgia (7% vs. 4%), rash, headache, and herpes viral infections.[6]
• In Crohn's Disease:
• Induction and Maintenance: The most common adverse reactions reported through 52 weeks included URTIs, injection site reactions, headache, arthralgia, and elevated liver tests.[6]

Warnings and Precautions

The prescribing information for Mirikizumab includes several important warnings and precautions that require clinical attention and patient monitoring.

• Hypersensitivity Reactions: Serious hypersensitivity reactions, including anaphylaxis, have been reported during intravenous infusion. Other infusion-related reactions such as mucocutaneous erythema and pruritus have also occurred. In the event of a severe hypersensitivity reaction, Mirikizumab must be discontinued immediately and appropriate medical treatment initiated.[6]
• Infections: As an immunomodulatory agent, Mirikizumab may increase the risk of infections by lowering the immune system's ability to fight them. Treatment should not be initiated in patients with a clinically important active infection. Patients with a history of chronic or recurrent infections should be considered for treatment with caution. If a patient develops a serious infection while on therapy, Mirikizumab should be withheld until the infection is resolved.[4]
• Tuberculosis (TB): Patients must be evaluated for tuberculosis infection prior to initiating Mirikizumab. Treatment is contraindicated in patients with active TB. If latent TB is diagnosed, treatment for TB must be initiated before starting Mirikizumab therapy.[4]
• Hepatotoxicity: Cases of drug-induced liver injury have been reported in clinical trials.[4] Therefore, it is recommended to obtain liver enzyme (transaminases) and bilirubin levels prior to initiating treatment. Patients should be monitored for signs and symptoms of liver injury (e.g., unexplained rash, nausea, fatigue, abdominal pain, jaundice, dark urine). If drug-induced liver injury is suspected, Mirikizumab should be interrupted until the diagnosis is excluded.[6] This specific warning and requirement for baseline testing underscores the importance of monitoring liver function with this agent.
• Immunizations: The use of live vaccines in patients receiving Mirikizumab should be avoided, as the immune response may be altered and the risk of infection from the vaccine increased. It is recommended that all age-appropriate vaccinations be brought up to date according to current immunization guidelines prior to starting therapy.[4]

Use in Special Populations

• Pregnancy: There is insufficient data from the use of Mirikizumab in pregnant women to establish a drug-associated risk. However, as an IgG monoclonal antibody, Mirikizumab is expected to be actively transported across the placenta, particularly during the third trimester. This could potentially lead to immunosuppression in the in utero-exposed infant.[1] A pregnancy exposure registry has been established to monitor maternal and fetal outcomes in women who are exposed to Mirikizumab during pregnancy.[10]
• Lactation: It is unknown whether Mirikizumab is excreted in human milk or absorbed systemically by a breastfed infant. Because Mirikizumab is a large protein molecule (approx. 147 kDa), the amount secreted into breast milk is likely to be very low. Furthermore, it would probably be degraded in the infant's gastrointestinal tract, leading to minimal systemic absorption.[39]

Global Regulatory Approvals and Market Access

U.S. Food and Drug Administration (FDA) Trajectory

Mirikizumab's path to approval in the United States involved an initial setback followed by successful approvals for both major IBD indications. In April 2023, Eli Lilly received a Complete Response Letter from the FDA for its initial Biologics License Application (BLA) for ulcerative colitis. This delay was not related to the clinical data on efficacy or safety but was due to issues identified during a pre-approval inspection related to the drug's manufacturing process.[6] This event highlights the critical importance of Chemistry, Manufacturing, and Controls (CMC) in the development of complex biologic products, where a robust and compliant manufacturing process is as crucial as clinical success for regulatory approval.

After successfully addressing the manufacturing concerns, Mirikizumab received its first FDA approvals:

• Ulcerative Colitis: Approval was granted on October 26, 2023, making Omvoh the first IL-23p19 antagonist to be approved for the treatment of moderately to severely active UC in the United States.[6]
• Crohn's Disease: Following the positive results of the VIVID-1 study, the FDA expanded the indication to include moderately to severely active Crohn's disease on January 15, 2025.[6]

European Medicines Agency (EMA) Trajectory

The regulatory process in the European Union proceeded smoothly, leading to timely approvals for both indications.

• Ulcerative Colitis: The Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion for the UC indication in March 2023.[7] This was followed by a full marketing authorization from the European Commission in May 2023.[7]
• Crohn's Disease: The CHMP adopted a positive opinion recommending approval for the CD indication on December 12, 2024. A final decision from the European Commission is anticipated in early 2025.[33]

Approvals in Other Regions

Mirikizumab has also achieved market access in other key regions, following a strategic global submission plan.

• Japan: The drug received its first global approval in Japan in March 2023 for the treatment of ulcerative colitis.[15]
• United Kingdom: The National Institute for Health and Care Excellence (NICE), which provides guidance for the National Health Service (NHS) in England, has recommended Mirikizumab as a treatment option for both ulcerative colitis (October 2023) and Crohn's disease (May 2025).[49]

Dosing, Formulations, and Clinical Administration

Available Formulations

Mirikizumab is provided as a sterile, preservative-free, clear to opalescent, colorless to slightly yellow or brown solution. It is available in several presentations to support the distinct induction and maintenance phases of treatment [1]:

• For Intravenous Infusion:
• Single-dose vial containing 300 mg of Mirikizumab in 15 mL of solution (concentration of 20 mg/mL).
• For Subcutaneous Injection:
• Single-dose prefilled pen or prefilled syringe containing 100 mg of Mirikizumab in 1 mL of solution (concentration of 100 mg/mL).
• Single-dose prefilled pen or prefilled syringe containing 200 mg of Mirikizumab in 2 mL of solution (concentration of 100 mg/mL). This formulation is indicated only for the maintenance treatment of Crohn's disease.[40]

Dosing and Administration Regimens

The recommended dosing for Mirikizumab is specific to each indication, with a higher dose required for the treatment of Crohn's disease compared to ulcerative colitis. This suggests that a greater level of drug exposure may be necessary to control the inflammatory processes in CD. The distinct dosing strategies are a critical consideration for clinical practice and have significant implications for treatment cost and logistics.

The following table details the approved dosing and administration schedules.

Phase	Indication	Dose	Route	Frequency / Schedule	Key Administration Details	Source(s)
Induction	Ulcerative Colitis	300 mg	Intravenous (IV) Infusion	Weeks 0, 4, and 8	Infuse over at least 30 minutes.	6
Induction	Crohn's Disease	900 mg	Intravenous (IV) Infusion	Weeks 0, 4, and 8	Infuse over at least 90 minutes.	6
Maintenance	Ulcerative Colitis	200 mg	Subcutaneous (SC) Injection	Week 12, then every 4 weeks	Administer as two consecutive 100 mg injections.	6
Maintenance	Crohn's Disease	300 mg	Subcutaneous (SC) Injection	Week 12, then every 4 weeks	Administer as two consecutive injections of 100 mg and 200 mg, in any order.	10

Preparation and Handling

Proper preparation and administration techniques are essential for the safety and efficacy of Mirikizumab.

• Intravenous Preparation: For administration by a healthcare provider, the required volume of Mirikizumab solution is withdrawn from the vial(s) and diluted into an infusion bag containing either 0.9% Sodium Chloride Injection or 5% Dextrose Injection. The bag should be gently inverted to mix and not shaken. The infusion should be started immediately after preparation, though the diluted solution is stable under refrigeration for a limited time.[40]
• Subcutaneous Administration: For maintenance therapy, patients or caregivers may self-inject Mirikizumab after receiving proper training. The prefilled pens or syringes should be removed from the refrigerator and allowed to warm to room temperature for 30-45 minutes before use. Injections should be administered into the abdomen, thigh, or back of the upper arm, and injection sites should be rotated with each dose. The devices should not be injected into skin that is tender, bruised, red, or hard.[41]

Therapeutic Positioning and Comparative Landscape

Mirikizumab's Place in IBD Treatment Algorithms

Mirikizumab is positioned as an advanced therapy for adult patients with moderately to severely active ulcerative colitis or Crohn's disease.[1] It is intended for patients who have had an inadequate response to, lost response to, or were intolerant of conventional therapies such as corticosteroids and immunomodulators, or other biologic treatments, most commonly TNF-alpha inhibitors.[1] Within the therapeutic armamentarium, it joins other classes of advanced treatments, including other biologics (e.g., anti-integrins, other interleukin inhibitors) and small molecule Janus kinase (JAK) inhibitors.[1] The choice among these agents is guided by factors such as prior treatment history, disease phenotype, safety considerations, patient preference, and payer access.

Comparative Analysis

The IBD market is a competitive space with multiple effective biologic agents. Understanding Mirikizumab's profile relative to key comparators is essential for clinical decision-making.

• vs. Ustekinumab (Stelara): Ustekinumab targets the p40 subunit shared by IL-12 and IL-23. The head-to-head data from the VIVID-1 trial in Crohn's disease showed that Mirikizumab was non-inferior for achieving clinical remission but failed to show non-inferiority for endoscopic response.[8] However, Mirikizumab demonstrated superiority in achieving histologic response, suggesting a deeper level of tissue healing.[35] This creates a nuanced choice for clinicians, balancing symptomatic control against different measures of mucosal healing. Economic models suggest that while ustekinumab may be less costly during induction, Mirikizumab is projected to be a more cost-effective option during long-term maintenance therapy.[52]
• vs. Risankizumab (Skyrizi): Risankizumab is another highly selective IL-23p19 inhibitor and is Mirikizumab's most direct competitor. Both have shown strong efficacy in Crohn's disease.[24] While they share a mechanism, they differ in their dosing regimens and approved indications (Risankizumab is also approved for psoriasis and psoriatic arthritis).[54] There are currently no head-to-head clinical trials comparing Mirikizumab and Risankizumab, and experts have identified this as a critical evidence gap needed to guide optimal positioning and sequencing of these two agents.[34]
• vs. Vedolizumab (Entyvio): Vedolizumab is an anti-integrin antibody that works by a distinct, gut-selective mechanism, preventing leukocyte trafficking into the intestinal tissue. This contrasts with Mirikizumab's systemic immunomodulatory approach. Indirect treatment comparisons suggest that Mirikizumab, vedolizumab, and ustekinumab have broadly similar efficacy in ulcerative colitis.[50] The choice between these agents often comes down to safety profiles (vedolizumab's gut-selectivity may be preferred in patients with a high risk of systemic infections) and patient-specific factors.

The following table provides a high-level comparison of Mirikizumab against these key biologic competitors in the IBD space.

Drug (Brand/Generic)	Mechanism of Action	Approved IBD Indications	Administration (Induction)	Administration (Maintenance)
Mirikizumab (Omvoh)	Selective IL-23p19 Inhibitor	Ulcerative Colitis, Crohn's Disease	IV Infusion (every 4 weeks x 3)	SC Injection (every 4 weeks)
Ustekinumab (Stelara)	IL-12 and IL-23 p40 Inhibitor	Ulcerative Colitis, Crohn's Disease	Single IV Infusion (weight-based)	SC Injection (every 8 weeks)
Risankizumab (Skyrizi)	Selective IL-23p19 Inhibitor	Ulcerative Colitis, Crohn's Disease	IV Infusion (every 4 weeks x 3)	SC Injection (every 8 weeks)
Vedolizumab (Entyvio)	α4​β7​ Integrin Antagonist	Ulcerative Colitis, Crohn's Disease	IV Infusion (Weeks 0, 2, 6)	IV Infusion or SC Injection (every 8 weeks)

Future Outlook and Unmet Needs

Ongoing and Future Clinical Research

Eli Lilly and Company is pursuing a robust clinical development program to further define the role of Mirikizumab and expand its potential applications.

• Pediatric IBD: Recognizing the significant need for effective and safe therapies for children and adolescents with IBD, the SHINE-ON master protocol (NCT04844606) is actively recruiting pediatric participants with either UC or CD to evaluate the drug in this population.[55]
• Long-Term Extension Studies: The LUCENT-3 (UC, NCT03519945) and VIVID-2 (CD) open-label extension studies are ongoing. These trials are critical for generating multi-year data on the durability of efficacy and the long-term safety profile, which is essential for building confidence in the chronic use of the therapy.[11]
• Innovative Combination Therapy: A novel Phase 3b study (NCT06937086) is currently recruiting patients with UC who also have comorbid obesity or are overweight. This trial will evaluate Mirikizumab administered concurrently with Tirzepatide, a dual GIP/GLP-1 receptor agonist widely used for type 2 diabetes and weight management.[56] This forward-thinking trial design moves beyond treating a single disease in isolation and explores a holistic approach that addresses the complex interplay between metabolic and autoimmune inflammation, potentially pioneering a new treatment paradigm.

Other Investigational Areas

Prior to its focus on IBD, Mirikizumab was extensively investigated as a treatment for plaque psoriasis. Multiple Phase 1, 2, and 3 clinical trials were completed for this indication.[58] While this did not lead to a regulatory approval for psoriasis, the data from these trials helped to establish the drug's mechanism and safety profile in other IL-23-mediated diseases.

Unmet Needs and Future Directions

Mirikizumab addresses several key unmet needs in IBD management, particularly its demonstrated ability to improve patient-reported outcomes like bowel urgency and its potential to induce deep, histologic remission, which may be associated with improved long-term outcomes and reduced risk of bowel damage.[9]

However, challenges remain. A critical need across all IBD therapies is the development of predictive biomarkers that can identify which patients are most likely to respond to a specific mechanism of action, allowing for more personalized and effective treatment selection from the outset. Another key question for the field is the efficacy of one IL-23 inhibitor after the failure of another. As both Mirikizumab and Risankizumab become more widely used, understanding their interchangeability and sequencing will be crucial.[34]

Finally, post-marketing efforts are focused on enhancing the patient experience. The development and study of a citrate-free formulation of Mirikizumab is a prime example. This new formulation was shown to be bioequivalent to the original commercial formulation but was associated with a lower frequency of injection site pain and reactions, representing a meaningful improvement in tolerability for patients on long-term subcutaneous therapy.[61] This focus on life-cycle management demonstrates a commitment to refining the product based on real-world patient feedback.

Conclusion

Mirikizumab (Omvoh) has emerged as a potent and selective inhibitor of the IL-23p19 pathway, establishing itself as a valuable new therapeutic option for adults with moderately to severely active ulcerative colitis and Crohn's disease. Its mechanism provides a targeted approach to suppressing a key driver of intestinal inflammation while sparing the IL-12 pathway.

The comprehensive LUCENT and VIVID clinical trial programs have demonstrated its efficacy in inducing and, crucially, maintaining clinical remission and endoscopic improvement over multiple years. The therapy has set a new standard by formally addressing and achieving significant improvements in the burdensome symptom of bowel urgency, reflecting a positive shift toward more patient-centric endpoints in IBD research. Furthermore, emerging data suggesting superiority in achieving histologic remission compared to an active comparator in Crohn's disease points toward its potential to induce a deeper level of mucosal healing, a key goal for preventing long-term disease progression.

With a manageable and well-characterized safety profile consistent with its drug class, and flexible formulations supporting both intravenous induction and subcutaneous maintenance, Mirikizumab is well-positioned within the competitive IBD therapeutic landscape. Ongoing research in pediatric populations and innovative combination therapies will further clarify its role. For clinicians and patients navigating the complexities of IBD management, Mirikizumab offers a durable, effective, and targeted treatment that addresses both objective measures of disease activity and the symptoms that matter most to patients.

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