Ulcerative colitis (UC) is a chronic
disease. UC is a type of inflammatory bowel disease (IBD). It is characterized
by inflammation and ulcerations of the colon and rectum resulting in the
symptoms of abdominal pain, diarrhea, increased stool frequency, increased
stool urgency, and rectal bleeding. Outside of the gastrointestinal (GI) tract,
symptoms can include eye conditions (redness, irritation), mouth ulcerations, skin
conditions (redness, swelling, rashes), and joint conditions (pain, swelling).
UC may have a slow onset and worsen over the course of weeks to months, or it
may start suddenly. Individuals with UC may experience periods of remission, lasting
weeks to years, where the symptoms improve, or they may have periods of mild,
moderate, or severe disease activity. Approximately 600,000 to 900,000 individuals
in the United States currently have UC. UC is more common in individuals between the ages
of 15 and 30 who have a first-degree relative with IBD. Complications of UC can
include anemia, dehydration, osteopenia/osteoporosis, delayed growth and
development in children, increased risk of colorectal cancer (CRC), intestinal
perforation, and fulminant UC or toxic megacolon. There is no cure for UC, so
the goal of therapy is the treatment of symptoms and disease remission.
Treatment may include medications with or without surgery.
Commonly used medications for
the treatment of UC include oral/topical aminosalicylates (e.g., balsalazide,
mesalamine, sulfasalazine), oral/topical corticosteroids, immunosuppressants
(e.g., methotrexate, 6-mercaptopurine [6-MP], azathioprine), sphingosine-1 phosphate (S1P) receptor modulators (e.g., ozanimod, etrasimod), Janus kinase
(JAK) inhibitors (e.g., tofacitinib, upadacitinib), and biologics (e.g., tumor
necrosis factor [TNF] blockers [e.g., infliximab, adalimumab, certolizumab, golimumab,
natalizumab], integrin receptor blockers [vedolizumab], interleukin [IL]-12 and IL-23
blockers [ustekinumab]).
Mirikizumab-mrkz
(Omvoh) is an immunoglobulin G4 (IgG4) monoclonal antibody that is
an IL-23 blocker. IL-23 is involved in mucosal inflammation. By
blocking IL-23, the treatment can inhibit the release of proinflammatory
cytokines and chemokines and thus ameliorate intestinal inflammation.
According to the US Food and
Drug Administration (FDA) label, the recommended dosage of mirikizumab-mrkz
(Omvoh) is 300 mg administered by intravenous (IV) infusion at weeks 0, 4, and
8 for induction therapy. The recommended maintenance dosage is 200 mg
administered by subcutaneous (SC) injection (administered as two injections of
100 mg each) at week 12, then every 4 weeks thereafter.
CLINICAL TRIALS
LUCENT-1
The safety and efficacy of mirikizumab-mrkz (Omvoh), used for induction, was evaluated in a
phase III, multicenter, randomized, double-blind, placebo-controlled
study (NCT03518086). A total of 1281 individuals with moderate to severe active
UC who had an inadequate response to, loss of response, or intolerance to
conventional or biologic therapy for UC were randomly assigned in a 3:1 ratio to mirikizumab-mrkz (Omvoh) or placebo. The
individuals received treatment at weeks 0, 4, and 8. The primary endpoint was
percentage of individuals who achieved clinical remission (defined as achieving
a modified Mayo score [MMS] subscore for rectal bleeding of 0, stool frequency
of 0 or 1 with 1 point or greater decrease from baseline, and endoscopy of 0 or
1 [excluding friability]) at 12 weeks. Secondary endpoints included percentage
of individuals with a clinical response at 12 weeks, percentage of individuals
with endoscopic remission at 12 weeks, percentage of individuals with histologic remission at 12 weeks, and percentage of individuals with endoscopic response at 12 weeks.
In the modified
intention-to-treat (mITT) population, 868 individuals received mirikizumab-mrkz
(Omvoh) and 294 individuals received placebo. At week 12, 24.2 percent of the
treatment group versus 13.3 percent of the placebo group achieved clinical
remission (99.875 percent confidence interval [CI], 3.2–19.1; P<0.001). At
week 12, 63.5 percent of the treatment group versus 42.2 percent of the placebo
group experienced a clinical response (99.875 percent CI, 10.8–32;
P<0.001). At week 12, 36.3 percent of the treatment group versus 21.1
percent of the placebo group demonstrated endoscopic remission (99.875 percent
CI, 6.3–24.5; P<0.001). At the end of 12 weeks, 27.1 percent of the
treatment group versus 13.9 percent of the placebo group demonstrated
histologic-endoscopic mucosal improvement (99.875 percent CI, 5.5–21.4; P<0.001).
LUCENT-2
The safety and efficacy of mirikizumab-mrkz (Omvoh), used for maintenance, was evaluated in a phase III, multicenter,
randomized, double-blind, placebo-controlled study (NCT03524092). Individuals
who had a clinical response to treatment with mirikizumab-mrkz (Omvoh) by week
12 in LUCENT-1 were randomly assigned again in a 2:1 ratio to receive maintenance
therapy with either mirikizumab-mrkz (Omvoh) or placebo, both administered
subcutaneously every 4 weeks for 40 weeks. The primary endpoint was
percentage of individuals who achieved clinical remission at week 40. Secondary
endpoints included percentage of individuals who achieved a glucocorticoid-free
clinical remission, the percentage of individuals who maintained clinical
remission, percentage of individuals who demonstrated endoscopic remission at
week 40, and percentage of individuals with histologic remission at 40 weeks.
A total of 365 individuals received
mirikizumab-mrkz (Omvoh) and 179 individuals received placebo. At week 40, 49.9
percent of the treatment group versus 25.1 percent of the placebo group achieved
clinical remission (95 percent CI, 15.2–to 31.2; P<0.001). At week 40, 44.9
percent of the treatment group and 21.8 percent of the placebo group had
achieved a glucocorticoid-free clinical remission (95 percent CI, 13.5–29.1;
P<0.001). At week 40, 63.6 percent of the treatment group and 36.9 percent
of the placebo group maintained clinical remission (95 percent CI, 10.4–39.2; P<0.001). At week 40, 58.6 percent of the treatment group and 29.1
percent of the placebo group demonstrated endoscopic remission (95 percent CI,
20.2–36.8; P<0.001). At week 40, 43.3 percent of the treatment group and
21.8 percent of the placebo group demonstrated histologic-endoscopic mucosal remission
(95 percent CI, 12.1–27.6; P<0.001).
LUCENT-3
The long-term safety and
efficacy of mirikizumab-mrkz (Omvoh) is being evaluated in an ongoing phase
III, multicenter, open-label extension study (NCT03519945). Individuals from
LUCENT-1 or LUCENT-2 are able to enroll in this long-term (160 weeks) study.
The primary endpoint is percentage of individuals who achieve clinical remission
at week 52. Secondary endpoints include percentage of individuals who achieve
endoscopic remission at week 52, percentage of individuals who achieve
corticosteroid-free remission at week 52, percentage of individuals who achieve
histologic-endoscopic mucosal remission at week 52, and percentage of
individuals who undergo UC surgeries (including colectomy) by week 160.
OFF-LABEL
INDICATIONS
There
may be additional indications contained in the Policy section of this document
due to evaluation of criteria highlighted in the Company's off-label policy,
and/or review of clinical guidelines issued by leading professional
organizations and government entities.