MIRIKIZUMAB-MRKZ (OMVOH)
Mirikizumab-mrkz (Omvoh) is an immunoglobulin G4 (IgG4) monoclonal antibody that is an interleukin (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.
ULCERATIVE COLITIS (UC)
UC is a chronic
disease. It is a type of inflammatory bowel disease (IBD). UC 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. UC is a relapsing, remitting disease. Individuals cycle
between symptoms of active disease and periods of remission. The severity ranges widely, from few
stools a day up to six or more with continuous bleeding and severe cramping. Most individuals have a mild
to moderate disease course, but about 10% to 15% experience more aggressive disease. Approximately 1.3 million individuals
in the United States currently have UC with the incidence peaking in the third degree of life and 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 (clinically and endoscopically).
Treatment may include medications with or without surgery.
Commonly used medications for the treatment of UC include oral and topical aminosalicylates (e.g., mesalamine, balsalazide, sulfasalazine), oral and topical corticosteroids, immunosuppressants (e.g., azathioprine, 6-mercaptopurine), sphingosine-1-phosphate (S1P) receptor modulators (e.g., ozanimod, etrasimod), Janus kinase (JAK) inhibitors (e.g., tofacitinib, upadacitinib), and biologic therapies, including tumor necrosis factor (TNF) inhibitors (e.g., infliximab, adalimumab, golimumab), integrin receptor antagonists (e.g., vedolizumab), IL-12/23 inhibitors (e.g., ustekinumab), and IL-23 inhibitors (e.g., mirikizumab, risankizumab, guselkumab).
CLINICAL TRIALS
LUCENT-1
The safety and efficacy of mirikizumab-mrkz (Omvoh), used for induction therapy for individuals
with UC, was evaluated in a
phase III, multicenter, randomized, double-blind, placebo-controlled
study (NCT03518086). A total of 1281 individuals with moderately to severely 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% of the
treatment group versus 13.3% of the placebo group achieved clinical
remission (99.875% confidence interval [CI], 3.2–19.1; P<0.001). At
week 12, 63.5% of the treatment group versus 42.2% of the placebo
group experienced a clinical response (99.875% CI, 10.8–32;
P<0.001). At week 12, 36.3% of the treatment group versus 21.1% of the placebo group demonstrated endoscopic remission (99.875% CI, 6.3–24.5; P<0.001). At the end of 12 weeks, 27.1% of the
treatment group versus 13.9% of the placebo group demonstrated
histologic-endoscopic mucosal improvement (99.875% CI, 5.5–21.4; P<0.001).
LUCENT-2
The safety and efficacy of mirikizumab-mrkz (Omvoh), used for maintenance therapy for individuals
with UC, 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 via the subcutaneous (SC) route 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% of the treatment group versus 25.1% of the placebo group achieved
clinical remission (95% CI, 15.2–to 31.2; P<0.001). At week 40, 44.9% of the treatment group and 21.8% of the placebo group had
achieved a glucocorticoid-free clinical remission (95% CI, 13.5–29.1;
P<0.001). At week 40, 63.6% of the treatment group and 36.9% of the placebo group maintained clinical remission (95% CI, 10.4–39.2; P<0.001). At week 40, 58.6% of the treatment group and 29.1% of the placebo group demonstrated endoscopic remission (95% CI,
20.2–36.8; P<0.001). At week 40, 43.3% of the treatment group and
21.8% of the placebo group demonstrated histologic-endoscopic mucosal remission
(95% CI, 12.1–27.6; P<0.001).
LUCENT-3
The long-term safety and
efficacy of mirikizumab-mrkz (Omvoh) therapy for individuals
with UC 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.
CROHN DISEASE
Crohn disease (CD) is a
chronic disease. It is a type of IBD. CD is characterized by inflammation in
the digestive tract, anywhere from the mouth to anus, but most commonly in the
small intestine and the beginning of the large intestine. Individuals may
experience flares, when symptoms are present, followed by periods of
remission, lasting weeks to years, during which the symptoms disappear. The symptoms
usually start slowly and can get worse over time. Common symptoms are diarrhea,
abdominal pain and cramping, and weight loss. Outside of the GI tract, symptoms
can include joint pain or arthritis, painful skin rashes or bumps, eye
irritation, the development of kidney stones, inflammation of the lungs that
can lead to difficulty breathing, or inflammation of the liver and bile ducts
that can cause primary sclerosis cholangitis. It is estimated that 1 million
individuals in the United States have CD. CD is more common in individuals between the
ages of 13 to 30, who have a family member with IBD, who smoke cigarettes, or are of
Jewish descent. Complications of CD can include anemia, osteoporosis or
osteopenia, delayed growth and development, or malnutrition. Serious
complications can include intestinal obstruction, the formation of fistulas, or
the development of abscesses, anal fissures, or ulcers anywhere along the GI
tract. Individuals with CD are also more likely to develop CRC. There is no cure for CD, so the goal of treatment is to maintain remission.
Treatments may include medication with or without surgery.
Commonly
used medications for the treatment of CD are similar to those used for UC and
can include corticosteroids, immunosuppressants, and biologics. However, not
all medications that treat UC can also be used to treat CD. Other medications
can include drugs to treat the symptoms, or complications, of the disease. Up
to 85% of individuals with CD will eventually require some form of
surgery to treat their symptoms or complications.
CLINICAL
TRIALS
VIVID-1
The safety
and efficacy of mirikizumab-mrkz (Omvoh), used for induction therapy for
individuals with CD, was evaluated in a phase III, multicenter, randomized,
double-blind, placebo- and active-controlled study (NCT03926130). A total of 1065
individuals from the efficacy population with moderately to severely active CD
who had an inadequate response to, loss of response, or intolerance to
conventional or biologic therapy for CD were randomly assigned, in a 6:3:2
ratio, to one of three cohorts. Cohort 1 (n=579) received mirikizumab-mrkz (Omvoh) IV
at weeks 0, 4, and 8, followed by treatment via the SC route every 4 weeks
starting at week 12 to week 52. Cohort 2 (n=287) received ustekinumab via the intravenous (IV) route at week 0, followed by treatment via the SC route every 8 weeks starting at week 8 onwards. Cohort 3 (n=199) received placebo in
the same manner as the mirikizumab-mrkz (Omvoh) cohort. At week 12, individuals
in Cohort 3 who did respond to placebo continued on placebo every 4 weeks. At
week 12, individuals in Cohort 3 who did not respond to placebo were switched
to the mirikizumab-mrkz (Omvoh) regimen starting with three IV doses every 4 weeks
followed by SC doses every 4 weeks onwards; their results were
included in composite endpoints of individuals who received mirikizumab-mrkz
(Omvoh). Eighty of 199 participants in
Cohort 3 were switched to treatment with mirikizumab-mrkz (Omvoh). The
coprimary endpoints were 1) the percentage of participants who achieved
clinical response at week 12 and endoscopic response at week 52, and 2) the
percentage of participants who achieved clinical response at week 12 and
clinical remission at week 52. Key secondary endpoints included endoscopic
response at week 12, corticosteroid-free clinical remission at week 52, and
endoscopic remission at week 52. These endpoints were assessed in Cohort 1 and
Cohort 3. A separate noninferiority endpoint, comparing individuals in Cohort
1 to Cohort 2, assessed clinical remission by CD activity index
(CDAI) at week 52. A separate superiority endpoint, comparing individuals in
Cohort 1 to Cohort 2, assessed endoscopic response at 52 weeks.
At week
12, 409 of 579 (70.6%) of participants in Cohort 1 versus 103 of 199 (51.8%) of participants in Cohort 3 experienced clinical response (difference,
18.9% [99.5% CI, 7.5–30.3];
P<0.0001). At week 52, 280 of 579 (48.4%) of participants in Cohort 1
versus 18 of 199 (9%) of participants in Cohort 3 experienced endoscopic
response (difference, 39.1% [99.5% CI, 31.0–47.2]; P<0.0001).
At week 52, 313 of 579 (54.1%) of participants in Cohort 1 versus 39 of 199 (19.6%) of participants in Cohort 3 experienced clinical remission by CDAI
(difference, 34.6% [99.5% CI, 24.7–44.4]; P<0.0001). At week
12, 188 of 579 (32.5%) of participants in Cohort 1 versus 25 of 199 (12.6%) of participants in Cohort 3 achieved endoscopic response (difference,
19.7% [99.5% CI, 11.1–28.2]; P<0.0001. By week 52, 253 of 579
(43.7%) of participants in Cohort 1 versus 37 of 199 (18.6%) of
participants in Cohort 3 achieved corticosteroid-free clinical remission
(difference, 25.0% [99.5% CI, 15.2–34.7]; P<0.0001). At week
52, 95 of 579 (15.9%) of participants in Cohort 1 versus four of 199 (2.0%) of participants in Cohort 3 achieved endoscopic remission (difference,
13.8% [99.5% CI, 8.7–18.9]; P<0.0001). For the
noninferiority endpoint, 313 of 579 (54.1%) of participants in Cohort 1
versus 139 of 287 (48.4%) of participants in Cohort 2 achieved clinical
remission by CDQI by week 52 (difference, 5.7% [95% CI, −1.4 to 12.8]).
For the superiority endpoint, 280 of 579 (48.4%) of participants in Cohort
1 versus 133 of 287 (46.3%) of participants in Cohort 2 achieved endoscopic
response at week 52 (difference, 2.3% [95% CI, −4.7 to 9.3];
P=0.51). In the safety population (n=1150) of all participants who received at
least one dose of the randomized treatment, most adverse event rates were higher
in the Cohort 3 than in Cohort 1. Exceptions of interest were injection site
reactions (65 of 630 [10.8%] versus seven of 211 [6.5%]), hypersensitivity
reactions (50 of 630 [7.9%] versus 11 of 211 [5.2%]), and opportunistic
infections (seven of 630 [1.1%] versus zero of 211 [0%]) when comparing Cohort
3 to Cohort 1. There were three deaths in participants in the clinical
trial: one individual in Cohort 3 due to a pulmonary embolism, one individual
in Cohort 3 who was switched to treatment with mirikizumab-mrkz (Omvoh) due to
disease worsening, and one individual in Cohort 2 due to Escherichia coli
sepsis; none of the deaths were considered to be caused by the study drug or the clinical
trial.
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.
