Mirikizumab-mrkz (Omvoh)

Number: 1048

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Brand Selection for Medically Necessary Indications for Commercial Medical Plans

As defined in Aetna commercial policies, health care services are not medically necessary when they are more costly than alternative services that are at least as likely to produce equivalent therapeutic or diagnostic results. Omvoh is more costly to Aetna than other targeted immune modulators for certain indications. There is a lack of reliable evidence that Omvoh is superior to the lower cost targeted immune modulators for the medically necessary indications listed below. Therefore, Aetna considers Omvoh to be medically necessary only for members who have a contraindication, intolerance or ineffective response to the available equivalent alternative targeted immune modulators per criteria below.

Moderately to Severely Active Crohn's Disease (CD)

For the treatment of CD, member has a contraindication, intolerance or ineffective response to all of the following available equivalent alternative targeted immune modulators (one-month trial each): Entyvio, Skyrizi, either PyzchivaFootnote* or Stelara, Tremfya, and either Avsola, Inflectra, or Renflexis.

Moderately to Severely Active Ulcerative Colitis (UC)

For the treatment of UC, member has a contraindication, intolerance or ineffective response to all of the following available equivalent alternative targeted immune modulators (one-month trial each): Entyvio, Skyrizi, either PyzchivaFootnote* or Stelara, Tremfya, and either Avsola, Inflectra or Renflexis.

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses mirikizumab-mrkz (Omvoh) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of mirikizumab-mrkz (Omvoh) is required of all Aetna participating providers and members in applicable plan designs. For precertification of mirikizumab-mrkz (Omvoh), call (866) 752-7021 or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification. 

1. Prescriber Specialties

   This medication must be prescribed by or in consultation with a gastroenterologist.

2. Criteria for Initial Approval

   Aetna considers mirikizumab-mrkz (Omvoh) medically necessary for the following indications:

   1. Treatment of moderately to severely active ulcerative colitis;
   2. Treatment of moderately to severely active Crohn's disease.

   Aetna considers all other indications as experimental, investigational, or unproven.

3. Continuation of Therapy

   Aetna considers continuation of mirikizumab-mrkz (Omvoh) therapy medically necessary for the following indications:

   1. Ulcerative colitis (UC)

      1. All members (including new members) who are using the requested medication for moderately to severely active ulcerative colitis and who achieve or maintain remission; or
      2. All members (including new members) who are using the requested medication for moderately to severely active ulcerative colitis and who achieve or maintain a positive clinical response as evidenced by low disease activity or improvement in signs and symptoms of the condition when there is improvement in any of the following from baseline:
         
         
         1. Stool frequency; or
         2. Rectal bleeding; or
         3. Urgency of defecation; or
         4. C-reactive protein (CRP); or
         5. Fecal calprotectin (FC); or
         6. Appearance of the mucosa on endoscopy, computed tomography enterography (CTE), magnetic resonance enterography (MRE), or intestinal ultrasound; or
         7. Improvement on a disease activity scoring tool (e.g., Ulcerative Colitis Endoscopic Index of Severity [UCEIS], Mayo score);

   2. Crohn's disease (CD)

      1. For all members (including new members) who are using the requested medication for moderately to severely active Crohn’s disease and who achieve or maintain remission; or
      2. For all members (including new members) who are using the requested medication for moderately to severely active Crohn’s disease and who achieve or maintain a positive clinical response as evidenced by low disease activity or improvement in signs and symptoms of the condition when there is improvement in any of the following from baseline:
         
         
         1. Abdominal pain or tenderness; or
         2. Diarrhea; or
         3. Body weight; or
         4. Abdominal mass; or
         5. Hematocrit; or
         6. Appearance of the mucosa on endoscopy, computed tomography enterography (CTE), magnetic resonance enterography (MRE), or intestinal ultrasound; or
         7. Improvement on a disease activity scoring tool (e.g., Crohn’s Disease Activity Index [CDAI] score).

4. Other 

   Member has been evaluated for tuberculosis (TB) infection prior to initiation of treatment with a biologic or targeted synthetic drug associated with an increased risk of TB.

   Member cannot use the requested medication concomitantly with any other biologic drug or targeted synthetic drug for the same indication.

5. Related Policies 

   1. CPB 0249 - Inflammatory Bowel Disease: Serologic Markers and Pharmacogenomic and Metabolic Assessment of Thiopurine Therapy
   2. CPB 0341 - Infliximab
   3. CPB 0655 - Adalimumab
   4. CPB 0761 - Certolizumab Pegol (Cimzia)
   5. CPB 0790 - Golimumab (Simponi and Simponi Aria)
   6. CPB 0885 - Vedolizumab (Entyvio)
   7. CPB 0912 - Ustekinumab
   8. CPB 1009 - Risankizumab-rzaa (Skyrizi)
   9. CPB 1011 - Guselkumab (Tremfya)

Dosage and Administration

Note: Approvals may be subject to dosing limits in accordance with FDA-approved labeling, accepted compendia, and/or evidence-based practice guidelines. Below includes dosing recommendations as per the FDA-approved prescribing information.

Omvoh is supplied in the following dosage forms and strengths:

• Intravenous (IV) infusion: 300 mg/15 mL (20 mg/mL) solution in a single-dose vial
• Subcutaneous (SC) injection:
  
  
  • 100 mg/mL solution in a single-dose prefilled pen and prefilled syringe
  • 200 mg/2 mL solution in a single-dose prefilled pen
  • 200 mg/2 mL (100 mg/mL) solution in a single-dose prefilled syringe

Ulcerative Colitis

• Induction dosage: 300 mg administered by IV infusion over at least 30 minutes at Week 0, Week 4, and Week 8. IV use is intended to be administered by a healthcare professional.
• Maintenance dosage: 200 mg administered by SC injection (given as two consecutive injections of 100 mg each) at Week 12, and every 4 weeks thereafter. A full maintenance dose will require 2 prefilled pens or 2 prefilled syringes. Individuals may self-inject after training in SC injection technique under the guidance and supervision of a healthcare professional.

Crohn's Disease

• Induction dosage: 900 mg administered intravenously over at least 90 minutes at Week 0, Week 4, and Week 8.
• Maintenance dosage: 300 mg subcutaneously (given as two consecutive injections of 100 mg and 200 mg in any order) at Week 12 and every 4 weeks thereafter. A full maintenance dose will require 2 prefilled pens or 2 prefilled syringes. Individuals may self-inject after training in SC injection technique under the guidance and supervision of a healthcare professional.

Source: Eli Lilly, 2025

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
71045 – 71048	Radiologic examination, chest
87116	Culture, tubercle or other acid-fast bacilli (e.g., TB, AFB, mycobacterial) any source, with isolation and presumptive identification of isolates
86480	Tuberculosis test, cell mediated immunity antigen response measurement; gamma interferon
86481	enumeration of gamma interferon-producing T-cells in cell suspension
86580	Skin test; tuberculosis, intradermal [Mantoux]
87556	Infectious agent detection by nucleic acid (DNA or RNA); Mycobacteria tuberculosis, amplified probe technique
87798	Infectious agent detection by nucleic acid (DNA or RNA), not otherwise specified; amplified probe technique, each organism [GeneXpert MTB/RIF]
96365 – 96368	Intravenous infusion, for therapy, prophylaxis, or diagnosis (specify substance or drug)
96372	Therapeutic, prophylactic, or diagnostic injection (specify substance or drug); subcutaneous or intramuscular
96401	Chemotherapy administration, subcutaneous or intramuscular; non-hormonal anti-neoplastic
96413 – 96415	Chemotherapy administration, intravenous infusion technique
HCPCS codes covered if selection criteria are met:
J2267	Injection, mirikizumab-mrkz, 1 mg
ICD-10 codes covered if selection criteria are met:
K50.00-K50.919	Crohn's disease [regional enteritis]
K51.00 - K51.919	Ulcerative colitis [moderately to severely active]

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Background

U.S. Food and Drug Administration (FDA)-Approved Indications 

• Treatment of moderately to severely active ulcerative colitis in adults;
• Treatment of moderately to severely active Crohn's disease in adults.

Mirikizumab-mrkz, an interleukin-23 antagonist, is branded as Omvoh (Eli Lilly and Company). Omvoh is a biologic medication that works by blocking the activity of interleukin-23 (IL-23), a cytokine with pro-inflammatory properties that is involved in mucosal inflammation. 

Mirikizumab-mrkz is a humanized IgG4 monoclonal antibody that targets p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor. IL-23 is involved in mucosal inflammation and affects the differentiation, expansion, and survival of T cell subsets, and innate immune cell subsets, which represent sources of pro-inflammatory cytokines. Mirikizumab-mrkz stops the IL-23 pathway, inhibiting the release of cytokines and chemokines responsible for the inflammation linked to ulcerative colitis and Crohn's disease.

The label for Omvoh carries warnings and precautions for hypersensitivity reactions, risk of infection, and hepatotoxicity. Serious hypersensitivity reactions, including anaphylaxis during intravenous infusion, have been reported with Omvoh administration.

Omvoh should not be administered to patients with active tuberculosis (TB) infection. Per the prescribing information, treatment of latent TB should be initiated prior to administering Omvoh. Consider anti-TB therapy prior to initiation of Omvoh in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. In addition, patients should be monitored for signs and symptoms of active TB during and after Omvoh treatment.  

Patients receiving Omvoh should avoid use of live vaccines. Medications that interact with the immune system may increase the risk of infection following administration of live vaccines.

The most common adverse reactions (2% or more) for persons with ulcerative colitis who received an induction dose included upper respiratory tract infections and arthralgia. For persons who received maintenance dose of Omvoh, the most common adverse reactions (2% or more) included upper respiratory tract infections, injection site reactions, arthralgia, rash, headache, and herpes viral infection.  

The most common adverse reactions (5% or more) for persons with Crohn's disease include upper respiratory infections, injection site reactions, headache, arthralgia, and elevated liver tests.

Available data from case reports of mirikizumab-mrkz use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

The safety and effectiveness of Omvoh has not been established in pediatric patients. 

Ulcerative Colitis

Ulcerative colitis (UC) is a serious, chronic and progressive immune-mediated inflammatory bowel disease (IBD) in which the lining of the colon becomes inflamed and develops ulcers, leading to bleeding and diarrhea. The inflammation almost always affects the rectum and lower part of the colon, but it can affect the entire colon. Two main goals of treatment for UC are to achieve remission and maintain remission.

In October 2023, the FDA approved Omvoh (mirikizumab-mrkz) infusion (300 mg/15 mL)/injection (100 mg/mL) for the treatment of moderately to severely active UC in adults. FDA approval was based on the safety and efficacy outcomes from two randomized, double-blind, placebo-controlled, phase 3 clinical studies (LUCENT-1 and LUCENT-2) which met its primary and key secondary endpoints, including sustained clinical remission, for induction and maintenance use of mirikizumab-mrkz in adults with moderately to severely active UC. 

LUCENT-1 (NCT03518086)] was a 12-week induction study (n=1279) that was followed by a 40-week maintenance study (n=581) LUCENT-2 (NCT03524092), for a total of 52 week of continuous mirikizumab-mrkz therapy. The studies included adult patients with moderately to severely active UC who were biologic-naïve, or had inadequate response, loss of response, or failed to tolerate any of the following: corticosteroids, immunomodulators (6-mercaptopurine and azathioprine), biologic therapy (TNF blocker, vedolizumab) or Janus kinase inhibitors (JAKi, tofacitinib). Patients who were on concomitant UC therapies during LUCENT-1 were required to continue on stable doses of oral aminosalicylates and immunomodulators (6-mercaptopurine, azathioprine, methotrexate). Corticosteroid tapering was required for patients who were receiving corticosteroids at baseline and achieved clinical response in LUCENT-1. At baseline, 57% were biologic and JAKi naïve, 41% had failed at least one biologic, and 3% had failed a JAKi. 

In LUCENT-1, efficacy was evaluated in 1062 adult patients who were randomized 3:1 to receive mirikizumab-mrkz (300 mg) intravenous (IV) or placebo IV at Week 0, Week 4, and Week 8. Patients (n=506) who achieved clinical response at Week 12 were re-randomized 2:1 to receive mirikizumab-mrkz (200 mg) or placebo via subcutaneous injection every 4 weeks for another 40 weeks in the LUCENT-2 trial. Disease activity was assessed based on the modified Mayo score (mMS), which ranges from 0 to 9 and has three subscores that are each scored from 0 (normal) to 3 (most severe): stool frequency, rectal bleeding, and findings on centrally read endoscopy subscore. At baseline, patients had a mMS of 5 to 9, including a centrally read endoscopy subscore of 2 or 3. An endoscopy subscore of 2 was defined by marked erythema, absent vascular pattern, friability, and erosions; and a subscore of 3 was defined by spontaneous bleeding and ulceration. Patients had a median mMS of 7, and 58% had severely active disease (mMS of 7 to 9). The primary endpoint of both trials were clinical remission at Week 12 and Week 52, respectively. The secondary endpoints of LUCENT-1 were clinical response, endoscopic improvement, and histologic-endoscopic mucosal improvement (HEMI) at 12 weeks. The secondary endpoints of LUCENT-2 were endoscopic improvement, maintenance of clinical remission in patients who achieved clinical remission at 12 weeks, corticosteroid-free clinical remission, HEMI and bowel urgency improvement (defined as patients achieving a weekly average urgency numeric rating scale of 0 to 1) at 40 weeks (a total of 52 weeks of treatment). 

After 12 weeks of treatment, 24% (n=795) achieved clinical remission compared to 15% of placebo (n=267); 65% (n=795) achieved clinical response compared to 43% of placebo (n=267); 34% achieved endoscopic improvement compared to 21% of placebo; and 25% achieved HEMI compared to 14% of placebo.

At 40 weeks (for a total of 52 weeks of treatment), 51% (n=337) achieved clinical remission compared to 27% of placebo (n=169); 53% (n=208) of patients who were biologic and JAKi naive achieved clinical remission compared to 33% of placebo (n=109); 45% (n=121) of patients who had prior biologic or JAKi failure achieved clinical remission compared to 15% of placebo (n=59); 50% (n=337) achieved corticosteroid-free clinical remission compared to 27% of placebo (n=169); 58% (n=337) achieved endoscopic improvement compared to 30% of placebo (n=169); 66% (n=128) achieved maintenance of clinical remission in patients who achieved clinical remission at Week 12 compared to 40% of placebo (n=62); and 43% (n=337) achieved HEMI compared to 22% of placebo (n=169).

Per a post-hoc analysis, nearly all patients (99%) who achieved clinical remission at one year were steroid-free. Patients in steroid-free clinical remission were steroid-free for at least three months prior to the end of the 52-week assessment. Among those who achieved clinical remission at 12 weeks, approximately two-thirds (66%) of patients maintained clinical remission through one year of continuous treatment compared to placebo (40%) (Eli Lilly, 2023).

In summary, mirikizumab-mrkz (Omvoh) was found to be more effective than placebo in inducing and maintaining clinical remission in patients with moderately to severely active ulcerative colitis.

Crohn's Disease

Crohn's disease is a chronic inflammatory bowel disease (IBD) that affects any part of the digestive tract, from the mouth to the anus. It causes inflammation and damage to the lining of the intestines, leading to symptoms such as diarrhea, fever, abdominal pain and cramping, blood in the stools, weight loss, and fatigue.

On January 15, 2025, the FDA approved Omvho (mirikizumab-mrkz) for the treatment of moderately to severely active Crohn's disease in adults. Approval is based on outcomes from the Phase 3 VIVID-1 study that showed Omvoh worked better than a placebo in treating moderate to severe Crohn's disease in people who had an inadequate response, loss of response, or intolerance to corticosteroids, immunomodulators, and/or biologics.

VIVID-1 (NCT03926130) was a randomized, double-blind, placebo-controlled 52-week study that evaluated the safety and efficacy of mirikizumab in adult patients with moderately to severely active Crohn’s disease who had an inadequate response, loss of response, or intolerance to corticosteroids, immunomodulators (azathioprine, 6-mercaptopurine and methotrexate) and/or biologics (TNF blockers, integrin receptor antagonists). A total of 679 patients were included in the study (mirikizumab group, n=511; placebo, n=168). At baseline, 47% had a loss of response, inadequate response, or intolerance to one or more biologic therapy. Patients received mirikizumab 900mg by intravenous (IV) infusion at Week 0, Week 4 and Week 8 followed by a maintenance dose of 300mg by subcutaneous injection (SC) at Week 12 and then every 4 weeks (Q4W) for 40 weeks, or placebo. Patients randomized to placebo who did not achieve clinical response by patient-reported outcome at 12 weeks (40% of placebo patients) were subsequently switched to mirikizumab treatment. Clinical remission was defined as Crohn’s Disease Activity Index (CDAI) less than 150. Endoscopic response was defined as greater than 50% reduction from baseline in Simple Endoscopic Score for Crohn's disease (SES-CD) total score, based on central reading. Bowel urgency was also assessed with an Urgency Numeric Rating Scale (UNRS) of 0 to 10. The coprimary endpoints of clinical remission by CDAI and endoscopic response by SES-CD were assessed at Week 52. Both primary endpoints in VIVID-1 were achieved. At Week 52, 53% of patients treated with mirikizumab achieved clinical remission versus 36% of placebo (p<0.001), and 46% had visible healing of the intestinal lining (endoscopic response) versus 36% of placebo (p<0.001). Additionally, a greater proportion of patients treated with mirikizumab compared to placebo achieved clinical remission (34% versus 23%) and endoscopic remission (10% versus 4%) at Week 12.

The overall safety profile of mirikizumab in patients with moderately to severely active Crohn's disease was generally consistent with its known safety profile in patients treated for ulcerative colitis.

Patients who completed Week 52 of VIVID-1 and, in the investigator's opinion, would derive clinical benefit from treatment with mirikizumab, were enrolled in VIVID-2. In VIVID-2, the primary objective is to evaluate the long-term effect of mirikizumab in clinical remission by CDAI and endoscopic response at Week 52 of treatment in VIVID-2 (totaling 104 weeks of continuous treatment). Safety is being assessed from the first dose in VIVID-2. Open-label extension studies may have selection bias as patients who cannot tolerate treatment or do not respond may drop out of the study prior to the extension (Eli Lilly, 2025).

In summary, mirikizumab-mrkz (Omvoh) was found to be more effective than placebo in inducing and maintaining clinical remission in patients with moderately to severely active Crohn's disease.

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References