At three years, over 80% of patients with
moderately to severely active UC who were in remission with
mirikizumab sustained long-term remission and relief from
disruptive symptoms, including bowel urgency
Mirikizumab also helped over 50% of patients
with moderately to severely active Crohn's disease sustain
long-term endoscopic remission for up to five years
INDIANAPOLIS, Oct. 28,
2024 /PRNewswire/ -- Eli Lilly and Company
(NYSE: LLY) announced results from two, multi-year, Phase 3 studies
that showed patients treated with mirikizumab sustained stable,
long-term remission across two types of inflammatory bowel diseases
(IBD), ulcerative colitis (UC) and Crohn's disease. Data from the
two trials – LUCENT-3 in moderately to severely active UC and
VIVID-2 in moderately to severely active Crohn's disease – will be
presented at the American College of Gastroenterology (ACG) Annual
Meeting from October 25-30, 2024 in
Philadelphia.
Mirikizumab is an interleukin-23p19 (IL23p19) antagonist that
selectively binds to the p19 subunit of IL-23 and inhibits its
interaction with the IL-23 receptor. Inflammation due to the
overactivation of the IL-23 pathway plays a critical role in
pathogenesis of UC and Crohn's disease. Inflammation from UC
and Crohn's disease can lead to disruptive symptoms, including
bowel urgency, that can result in decreased health-related quality
of life and potentially irreversible complications for patients if
left untreated. Mirikizumab is approved in the United States (U.S.) for the treatment of
moderately to severely active UC in adults and is under review with
the U.S. Food and Drug Administration (FDA) for moderately to
severely active Crohn's disease.
"Mirikizumab is the first and only IL23p19 antagonist to report
multi-year, long-term sustained efficacy data in both ulcerative
colitis and Crohn's disease," said Mark
Genovese, M.D., senior vice president of Lilly Immunology
development. "This achievement reflects our commitment to help
people with immune system conditions sustain long-standing
remission and relieve disease burden."
Long-Term Data in Adults with UC
In LUCENT-3,
mirikizumab helped patients with moderately to severely active UC
achieve long-term outcomes, including histologic-endoscopic mucosal
remission, defined as mucosal healing. Mirikizumab also provided
sustained benefit across symptomatic, clinical, endoscopic and
histologic endpoints for up to three years, regardless of previous
failure to TNF inhibitors, tofacitinib or other
biologics. Among those who achieved clinical remission with
mirikizumab at one year in the LUCENT-2 study, the following
results were achieved based upon observed case analysis after an
additional two years of treatment (up to three years
total):
- 81% of patients maintained long-term clinical remission
- 82% achieved long-term endoscopic remission
- 72% had mucosal healing
- 79% achieved corticosteroid-free clinical remission
- Patients demonstrated a sustained clinically meaningful
improvement in symptom score reduction for bowel urgency
(-4.72)
These results were also evaluated using a modified non-responder
imputation and are presented in the About the Mirikizumab
Ulcerative Colitis Program section below.
Among patients receiving mirikizumab in the LUCENT-3 study,
7.4% of patients reported a serious adverse event (AE), while 5.3%
discontinued treatment due to an AE. The long-term safety profile
in patients with moderately to severely active UC was consistent
with the already known safety profile of mirikizumab. These data
were recently published in Inflammatory Bowel
Diseases.
Long-Term Data in Adults with Crohn's Disease
New data
from patients in the Phase 2 program who enrolled into the VIVID-2
long-term extension study showed that patients with moderately to
severely active Crohn's disease treated with mirikizumab maintained
high rates of clinical and endoscopic remission over time. The
following results were achieved based upon observed case analysis
after an additional three years of treatment (up to five years
total):
- 96% of patients had clinical response as measured by the
Crohn's Disease Activity Index (CDAI)
- 87% were in clinical remission as measured by CDAI
- 76% had endoscopic response
- 54% of patients were in endoscopic remission
These results were also evaluated using a modified non-responder
imputation and are presented in the About the Mirikizumab Crohn's
Disease Program section below.
"Despite continued advances, people living with ulcerative
colitis and Crohn's disease are still seeking treatments that can
address difficult-to-manage symptoms such as bowel urgency, and
provide lasting results over time," said Bruce Sands, M.D., M.S., Dr. Burrill B. Crohn
Professor of Medicine and Chief of the Dr. Henry D. Janowitz
Division of Gastroenterology, Icahn School of Medicine at Mount
Sinai. "These multi-year data show mirikizumab is a targeted
therapy that can provide intestinal healing over time and
improvement in key symptoms that matter most to
patients."
Among these patients who enrolled into the VIVID-2 long-term
extension study, 8.5% reported a serious AE and 1.9% discontinued
treatment due to an AE. The long-term safety profile in patients
with moderately to severely active Crohn's disease was consistent
with the already known safety profile of mirikizumab.
Omvoh® (mirikizumab-mrkz) was approved by the FDA in
October 2023 as the first IL23p19
antagonist for the treatment of moderately to severely active UC in
adults and is also approved in 44 countries around the world. Lilly
submitted marketing applications for mirikizumab in Crohn's disease
around the globe, including in the U.S., Canada, Europe, Japan
and China. Additional global
regulatory submissions are planned.
Additionally, Lilly has a combination study in UC with
mirikizumab and eltrekibart, a humanized monoclonal antibody that
binds to the seven ligands that signal through the CXCR1 and CXCR2
chemokine receptors involved in neutrophil movement to sites of
inflammation (NCT06598943). There are also ongoing studies in both
UC (NCT05611671) and Crohn's disease (NCT06226883) with MORF-057, a
selective oral small molecule alpha-4/beta-7 integrin inhibitor
that may improve outcomes and expand treatment options for people
with IBD.
Disclosure: Dr. Sands is a paid consultant for Lilly. He has
not been compensated for any media work.
About the Mirikizumab Ulcerative Colitis
Program
Mirikizumab was studied in two, Phase 3
clinical trials which evaluated the efficacy and safety of
mirikizumab in adults with moderately to severely active ulcerative
colitis (UC) and included patients who had never tried a biologic
(biologic-naïve) and harder-to-treat patients who had previously
taken a biologic that failed. The induction LUCENT-1 and
maintenance LUCENT-2 studies were randomized, double-blind, and
placebo-controlled and included those who 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). Additionally, 41% of
patients in LUCENT-1 had failed at least one biologic, 3% had
failed a JAKi and 57% were biologic and JAKi-naïve.
LUCENT-3, the ongoing long-term Phase 3 extension of LUCENT-1
and LUCENT-2 evaluated the efficacy and safety of mirikizumab in
patients with UC for up to three years. Using a modified
non-responder imputation analysis to handle discontinuation and
missing data, among Week 52 mirikizumab remitters, 70% maintained
long-term clinical remission at Week 152, and response rates for
major efficacy endpoints (including endoscopic remission,
histologic-endoscopic mucosal remission, corticosteroid-free
remission and clinical response) ranged from 63% to 85%.
About the Mirikizumab Crohn's Disease Program
VIVID-1 was a Phase 3, randomized, double-blind, treat-through
study that evaluated the safety and efficacy of mirikizumab
compared with placebo and an active control (ustekinumab) in adults
with moderately to severely active Crohn's disease. Patients
randomized to mirikizumab were administered 900 mg of mirikizumab
intravenously every four weeks from Week 0-12, then 300 mg
subcutaneously every four weeks from Weeks 12-52. In this study,
49% of patients taking mirikizumab or placebo had experienced a
prior biologic failure.
SERENITY, the Phase 2, multi-center, randomized, parallel-arm,
double-blind, placebo-controlled trial was designed to assess the
safety and efficacy of mirikizumab in patients with moderately to
severely active Crohn's disease. At baseline, participants were
randomized with a 2:1:1:2 allocation across four treatment arms
(placebo, mirikizumab 200 mg, mirikizumab 600 mg and mirikizumab
1000 mg). The primary endpoint was endoscopic response as
determined by the proportion of participants achieving at least 50%
reduction from baseline on the Simple Endoscopic Score for Crohn's
Disease (SES-CD) at Week 12. In May
2019, Lilly reported Phase 2 results showing more
patients with moderate to severe Crohn's disease receiving
mirikizumab compared with placebo achieved clinical response and
remission at 12 weeks. Overall, the safety profile at 12 weeks was
consistent with that of mirikizumab in studies of ulcerative
colitis and with the IL23p19 class.
VIVID-2, the ongoing long-term Phase 3 extension of SERENITY and
the VIVID-1 study, evaluated the efficacy and safety of mirikizumab
in patients with Crohn's disease for up to five years. Using a
modified non-responder imputation analysis to handle
discontinuation and missing data, 61% and 44% achieved endoscopic
response and endoscopic remission, respectively, at Week 156. In
addition, 79% and 72% achieved clinical response and clinical
remission, respectively, at Week 156.
Indications and Usage for
Omvoh® (mirikizumab-mrkz) (in the United States)
Omvoh® is indicated for the treatment of moderately
to severely active ulcerative colitis in adults.
Important Safety Information for Omvoh
(mirikizumab-mrkz)
CONTRAINDICATIONS - Omvoh is contraindicated in patients
with a history of serious hypersensitivity reaction to
mirikizumab-mrkz or any of the excipients.
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions
Serious hypersensitivity
reactions, including anaphylaxis during intravenous infusion, have
been reported with Omvoh administration. Infusion-related
hypersensitivity reactions, including mucocutaneous erythema and
pruritus, were reported during induction. If a severe
hypersensitivity reaction occurs, discontinue Omvoh immediately and
initiate appropriate treatment.
Infections
Omvoh may increase the risk of infection.
Do not initiate treatment with Omvoh in patients with a clinically
important active infection until the infection resolves or is
adequately treated. In patients with a chronic infection or a
history of recurrent infection, consider the risks and benefits
prior to prescribing Omvoh. Instruct patients to seek medical
advice if signs or symptoms of clinically important acute or
chronic infection occur. If a serious infection develops or an
infection is not responding to standard therapy, monitor the
patient closely and do not administer Omvoh until the infection
resolves.
Tuberculosis
Evaluate patients for tuberculosis (TB)
infection prior to initiating treatment with Omvoh. Do not
administer Omvoh to patients with active TB infection. Initiate
treatment of latent TB prior to administering Omvoh. Consider
anti-TB therapy prior to initiation of Omvoh in patients with a
history of latent or active TB in whom an adequate course of
treatment cannot be confirmed. Monitor patients for signs and
symptoms of active TB during and after Omvoh treatment. In clinical
trials, subjects were excluded if they had evidence of active TB, a
history of active TB, or were diagnosed with latent TB at
screening.
Hepatotoxicity
Drug-induced liver injury in
conjunction with pruritus was reported in a clinical trial patient
following a longer than recommended induction regimen. Omvoh was
discontinued. Liver test abnormalities eventually returned to
baseline. Evaluate liver enzymes and bilirubin at baseline and for
at least 24 weeks of treatment. Monitor thereafter according to
routine patient management. Consider other treatment options in
patients with evidence of liver cirrhosis. Prompt investigation of
the cause of liver enzyme elevation is recommended to identify
potential cases of drug-induced liver injury. Interrupt treatment
if drug-induced liver injury is suspected, until this diagnosis is
excluded. Instruct patients to seek immediate medical attention if
they experience symptoms suggestive of hepatic dysfunction.
Immunizations
Avoid use of live vaccines in patients
treated with Omvoh. Medications that interact with the immune
system may increase the risk of infection following administration
of live vaccines. Prior to initiating therapy, complete all
age-appropriate vaccinations according to current immunization
guidelines. No data are available on the response to live or
non-live vaccines in patients treated with Omvoh.
ADVERSE REACTIONS
Most common adverse reactions (≥2%)
associated with Omvoh treatment are upper respiratory tract
infections and arthralgia during induction, and upper respiratory
tract infections, injection site reactions, arthralgia, rash,
headache, and herpes viral infection during maintenance.
During induction, Omvoh is available as a single dose vial for
intravenous infusion containing 300 mg/15 mL that is administered
in a healthcare facility. During maintenance, Omvoh is available as
a one-time use prefilled pen or syringe with 100 mg/mL for
subcutaneous injections. See Prescribing Information for dosing
information.
MR HCP ISI 31JUL2024
Please click for Prescribing Information and Medication Guide
for Omvoh. Please click for Instructions for Use included with the
device.
About Omvoh®
Omvoh® (mirikizumab-mrkz) is an interleukin-23p19
antagonist indicated for the treatment of moderately to severely
active ulcerative colitis in adults. Omvoh selectively targets the
p19 subunit of IL-23 and inhibits the IL-23 pathway. Inflammation
due to over-activation of the IL-23 pathway plays a critical role
in the pathogenesis of ulcerative colitis. Treatment of ulcerative
colitis with Omvoh starts with 300-mg IV infusions, once every four
weeks for a total of three infusions, and transitions to two,
100-mg subcutaneous injections every four weeks during maintenance
treatment.
Omvoh and its delivery device base are trademarks owned by Eli
Lilly and Company.
About Lilly
Lilly is a medicine company turning science into healing to
make life better for people around the world. We've been pioneering
life-changing discoveries for nearly 150 years, and today our
medicines help tens of millions of people across the globe.
Harnessing the power of biotechnology, chemistry and genetic
medicine, our scientists are urgently advancing new discoveries to
solve some of the world's most significant health challenges:
redefining diabetes care; treating obesity and curtailing its most
devastating long-term effects; advancing the fight against
Alzheimer's disease; providing solutions to some of the most
debilitating immune system disorders; and transforming the most
difficult-to-treat cancers into manageable diseases. With each step
toward a healthier world, we're motivated by one thing: making life
better for millions more people. That includes delivering
innovative clinical trials that reflect the diversity of our world
and working to ensure our medicines are accessible and affordable.
To learn more, visit Lilly.com and Lilly.com/news,
or follow us
on Facebook, Instagram and LinkedIn. P-LLY
Cautionary Statement Regarding Forward-Looking
Statements
This press release contains forward-looking statements (as that
term is defined in the Private Securities Litigation Reform Act of
1995) about mirikizumab as a potential treatment for people with
moderately to severely active ulcerative colitis and Crohn's
disease and the timeline for future readouts, presentations, and
other milestones relating to mirikizumab and its clinical trials,
and reflects Lilly's current beliefs and expectations. However, as
with any pharmaceutical product, there are substantial risks and
uncertainties in the process of drug research, development, and
commercialization. Among other things, there is no guarantee that
planned or ongoing studies will be completed as planned, that
future study results will be consistent with study results to date,
that mirikizumab will prove to be a safe and effective treatment
for Crohn's disease, that mirikizumab will receive regulatory
approval, or that Lilly will execute its strategy as expected. For
further discussion of these and other risks and uncertainties that
could cause actual results to differ from Lilly's expectations, see
Lilly's Form 10-K and Form 10-Q filings with the United States
Securities and Exchange Commission. Except as required by law,
Lilly undertakes no duty to update forward-looking statements to
reflect events after the date of this release.
Refer to: Cathy Buck;
cathy.buck@lilly.com; +1-317-982-1153 (Lilly media)
Joe Fletcher;
jfletcher@lilly.com; 317-296-2884; (Lilly investors)
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