INDIANAPOLIS, April 23, 2021 /PRNewswire/ -- Through new
analyses of BREEZE-AD5 Phase 3 clinical trial data and an extended
safety analysis across multiple trials, Eli Lilly and Company
(NYSE: LLY) and Incyte's (NASDAQ:INCY) OLUMIANT®
(baricitinib) 2-mg tablet taken once daily showed improvement in
key measured treatment outcomes compared to placebo, and helped
further characterize the long-term safety profile in adults with
moderate to severe atopic dermatitis (AD). In one BREEZE-AD5
analysis, OLUMIANT provided concurrent improvements in the severity
and extent of AD, other key symptoms and quality of life as early
as one week, as measured by percent change from baseline compared
to placebo. In a separate BREEZE-AD5 analysis, adults with AD on
10-50% of their bodies at baseline who were treated with OLUMIANT
showed significant improvements in the severity and extent of
disease compared to placebo. In the integrated safety analysis of
eight AD studies of OLUMIANT, there were no increases in rates for
treatment-emergent adverse events, serious adverse events or
serious infections with long-term OLUMIANT therapy compared to the
placebo-controlled period. These results are being presented
virtually at the American Academy of Dermatology's Virtual Meeting
Experience (AAD VMX), April 23-25,
2021.
"Atopic dermatitis is the most common chronic, inflammatory skin
disease among adults and can pose significant challenges for those
who suffer from this debilitating disease," said Lotus Mallbris,
M.D., Ph.D., vice president of immunology development at Lilly. "We
are encouraged by these additional new analyses of the BREEZE-AD5
study results, in which OLUMIANT showed early improvement across
multiple symptoms among patients with moderate to severe atopic
dermatitis. We are pleased the extended safety analysis helps
further define the long-term safety profile of OLUMIANT in atopic
dermatitis."
OLUMIANT 2-mg Concurrently Improved Extent, Severity and Key
Symptoms of AD in as Early as One Week
In a post-hoc analysis of BREEZE-AD5, patients treated with
OLUMIANT 2-mg showed statistically significant and concurrent
improvements in the extent and severity of AD, as well as key
symptoms such as itch, nighttime awakenings due to itch, skin
discomfort and pain, and quality of life, as early as one week as
measured by percent change from baseline compared to placebo.
Patients taking OLUMIANT had statistically significant improvements
from baseline (p<0.05) across all measures compared to placebo
at one week and four weeks:
- Skin Measures:
-
- Eczema Area and Severity Index (EASI), which is a validated,
clinical scoring system measuring the extent and severity of
AD:
-
- At one week: 25.3% for OLUMIANT vs. 7.2% for placebo
- At four weeks: 50.9% for OLUMIANT vs. 24.0% for placebo
- Key Symptoms:
-
- Itch Numeric Rating Scale (NRS):
-
- At one week: 13.5% for OLUMIANT vs. -0.2% for placebo
- At four weeks: 29.0% for OLUMIANT vs. 12.5% for placebo
- Skin Pain NRS (Skin discomfort and pain):
-
- At one week: 12.0% for OLUMIANT vs. 2.6% for placebo
- At four weeks: 27.6% for OLUMIANT vs. 13.6% for placebo
- AD Sleep Scale (ADSS) Item 2 (number of nighttime awakenings
due to itch):
-
- At one week: 20.9% for OLUMIANT vs. 3.9% for placebo
- At four weeks: 37.6% for OLUMIANT vs. 14.1% for placebo
- Composite Outcomes, Including Quality of Life:
-
- Dermatology Life Quality Index (DLQI):
-
- At one week: 27.2% for OLUMIANT vs. 12.9% for placebo
- At four weeks: 40.4% for OLUMIANT vs. 17.5% for placebo
- Patient Oriented Eczema Measure (POEM):
-
- At one week: 18.0% for OLUMIANT vs. 6.7% for placebo
- At four weeks: 29.3% for OLUMIANT vs. 10.8% for placebo
For methodology, see "About the Analyses" section below.
Patients with AD on 10-50% of Their Bodies at Baseline
Treated with OLUMIANT 2-mg Experienced Significant Improvements in
Severity and Extent of AD
A post-hoc analysis of BREEZE-AD5 was conducted to evaluate the
efficacy of OLUMIANT 2-mg based on baseline Body Surface Area
(BSA), which measures the extent to which a patient's skin is
affected by AD. At two weeks, 2 out of 10 patients with a BSA
10-50% at baseline who were treated with OLUMIANT saw significant
improvements in the severity and extent of their AD compared to
placebo (20.2% vs. 5.9%, p≤0.01), as measured by a 75% improvement
in Eczema Area Severity Index (EASI 75).
At 16 weeks, nearly 4 out of 10 patients with a BSA 10-50% at
baseline who were treated with OLUMIANT saw significant
improvements in the severity and extent of their AD compared to
placebo (37.5% vs. 9.9%, p≤0.001) as measured by EASI 75.
At 16 weeks, approximately 3 out of 10 patients with a BSA
10-50% at baseline who were treated with OLUMIANT saw significant
improvements in the severity and extent of the AD compared to
placebo (31.7% vs. 6.9%, p≤0.001) based on achievement of clear or
almost clear skin, as measured by the validated Investigator Global
Assessment for Atopic Dermatitis [vIGA-AD (0,1)].
OLUMIANT was also evaluated in patients with BSA >50% at
baseline. Among these patients, results for OLUMIANT were
numerically higher but not statistically significant compared to
placebo. Safety for the baseline BSA 10-50% subgroup was consistent
with the overall safety population across the OLUMIANT clinical
program in AD.
For methodology, see "About the Analyses" section below.
"Patients with moderate to severe atopic dermatitis may have
different treatment needs given the extent and severity of their
disease," said Eric Simpson, M.D.,
M.C.R., Professor of Dermatology and Director of Clinical Research
at Oregon Health & Science University in Portland and co-author of these analyses.
"These results are exciting because they can help provide more
clarity to dermatologists on how patients with atopic dermatitis on
10-50% of their bodies may respond to a systemic therapy, such as
OLUMIANT."
Long-Term Analysis Supports Safety Profile of OLUMIANT 2-mg
in AD
The safety profile for OLUMIANT 2-mg was evaluated in eight AD
clinical studies (six double-blind, randomized, placebo-controlled
studies and two long-term extension studies). In the 16-week
placebo-controlled period, there was no observed increase in rates
of serious adverse events or serious infections with OLUMIANT
therapy compared to placebo, and rates remained similar in the
long-term extensions. There were no reports of deep vein thrombosis
and pulmonary embolism across these studies.
OLUMIANT showed no increase in anemia, neutropenia, lymphopenia
or elevated liver enzymes compared to placebo as measured by mean
change from baseline, and there was no additional increase in these
lab changes with long-term therapy. There was no increase in
risk of eczema herpeticum with OLUMIANT compared to placebo (0.2%
vs. 0.4%), but an increase in cases of herpes simplex (2.0% vs.
0.9%) was observed.
For methodology, see "About the Analyses" section below.
"Given how challenging this multidimensional disease is to
treat, patients with AD need additional options that can help them
manage their disease when other therapies have not been effective,"
Dr. Mallbris continued. "OLUMIANT has the potential to be the first
oral JAK inhibitor approved for adults with moderate to severe
atopic dermatitis in the U.S. When approved, it would also have one
of the largest sets of available safety data in its class for
AD."
About The Analyses
- Rapid and Concurrent Improvements in the Signs and Symptoms
of Atopic Dermatitis with Baricitinib in the Phase 3 Study,
BREEZE-AD5
-
- 440 patients from the Phase 3 BREEZE-AD5 trial were randomized
1:1:1 to once-daily placebo or OLUMIANT 1-mg or 2-mg. Percent
changes from baseline were assessed for the following measures in
the first four weeks of the study: EASI, itch NRS, skin pain NRS,
ADSS item 2, DLQI and POEM. P-values shown above were not adjusted
for multiplicity.
- Efficacy of Baricitinib 2-mg Stratified by Baseline Body
Surface Area in Adults with Moderate to Severe Atopic
Dermatitis
-
- In a post-hoc analysis, 293 patients from the Phase 3
BREEZE-AD5 trial were divided into subgroups of baseline BSA 10-50%
and >50%. Subgroups were evaluated for the proportion of
patients achieving a ≥75% reduction in EASI (EASI 75) and vIGA-AD™
(0,1). Safety was also assessed in the subgroup of patients with
BSA 10-50% at baseline. P-values shown above were not adjusted for
multiplicity.
- Extended Safety Analysis of Baricitinib 2-mg in Adult
Patients with Atopic Dermatitis: An Integrated Analysis from 8
Randomized Clinical Trials
-
- OLUMIANT 2-mg was studied in six double-blind, randomized,
placebo-controlled studies and two long-term extension studies.
Incidence rates (IR)/100 patient-years at risk (PYR) were
calculated. The analysis included 1,598 patients who received
OLUMIANT 2-mg for 1,434.2 combined patient years of exposure
(median 330 days).
OLUMIANT, an oral JAK inhibitor discovered by Incyte and
licensed to Lilly, is currently under review by the U.S. Food and
Drug Administration as an investigational medication for the
treatment of adults with moderate to severe AD. Outside the U.S.,
it is the first JAK inhibitor approved for AD in more than 40
countries. It is also being investigated for the treatment of
adults with alopecia areata, systemic lupus erythematosus, juvenile
idiopathic arthritis, COVID-19 and for its approved indication for
rheumatoid arthritis.
About OLUMIANT®
OLUMIANT is a once-daily,
oral JAK inhibitor approved in the U.S. and more than 70
countries as a treatment for adults with moderate to severe
rheumatoid arthritis (RA). It is also approved in the European
Union, Japan and other countries for the treatment of
adult patients with moderate to severe atopic dermatitis who are
candidates for systemic therapy. The U.S. FDA-approved
labeling for Olumiant includes a Boxed Warning for Serious
Infections, Malignancy, and Thrombosis. See the full Prescribing
Information here.
In December
2009, Lilly and Incyte announced an exclusive
worldwide license and collaboration agreement for the development
and commercialization of baricitinib and certain follow-on
compounds for patients with inflammatory and autoimmune
diseases.
Indication and Usage for OLUMIANT (baricitinib) tablets (in
the United States) for RA
patients
OLUMIANT® (baricitinib) 2-mg is indicated for
the treatment of adult patients with moderately to severely active
rheumatoid arthritis who have had an inadequate response to one or
more tumor necrosis factor (TNF) antagonist therapies. Limitation
of Use: Use of OLUMIANT in combination with other JAK inhibitors,
biologic disease-modifying antirheumatic drugs (DMARDs), or with
potent immunosuppressants such as azathioprine and cyclosporine is
not recommended.
IMPORTANT SAFETY INFORMATION FOR OLUMIANT (baricitinib)
tablets
WARNING: SERIOUS INFECTIONS, MALIGNANCY, AND
THROMBOSIS
SERIOUS INFECTIONS: Patients treated with Olumiant are at
risk for developing serious infections that may lead to
hospitalization or death. Most patients who developed these
infections were taking concomitant immunosuppressants such as
methotrexate or corticosteroids. If a serious infection develops,
interrupt Olumiant until the infection is controlled. Reported
infections include:
- Active tuberculosis (TB), which may present with pulmonary
or extrapulmonary disease. Test patients for latent TB before
initiating Olumiant and during therapy. If positive, start
treatment for latent infection prior to Olumiant use.
- Invasive fungal infections, including candidiasis and
pneumocystosis. Patients with invasive fungal infections may
present with disseminated, rather than localized, disease.
- Bacterial, viral, and other infections due to opportunistic
pathogens.
Carefully consider the risks and benefits of Olumiant prior
to initiating therapy in patients with chronic or recurrent
infection.
Closely monitor patients for the development of signs and
symptoms of infection during and after treatment with Olumiant
including the possible development of TB in patients who tested
negative for latent TB infection prior to initiating
therapy.
MALIGNANCIES: Lymphoma and other malignancies have been
observed in patients treated with Olumiant.
THROMBOSIS: Thrombosis, including deep venous thrombosis
(DVT) and pulmonary embolism (PE), has been observed at an
increased incidence in patients treated with Olumiant compared to
placebo. In addition, there were cases of arterial thrombosis. Many
of these adverse events were serious and some resulted in death.
Patients with symptoms of thrombosis should be promptly
evaluated.
WARNINGS AND PRECAUTIONS
SERIOUS INFECTIONS: The most common serious
infections reported with Olumiant included pneumonia, herpes
zoster, and urinary tract infection. Among opportunistic
infections, tuberculosis, multidermatomal herpes zoster, esophageal
candidiasis, pneumocystosis, acute histoplasmosis, cryptococcosis,
cytomegalovirus, and BK virus were reported with Olumiant. Some
patients have presented with disseminated rather than localized
disease, and were often taking concomitant immunosuppressants such
as methotrexate or corticosteroids. Avoid Olumiant in patients with
an active, serious infection, including localized infections.
Consider the risks and benefits of treatment prior to initiating
Olumiant in patients:
- with chronic or recurrent infection
- who have been exposed to TB
- with a history of a serious or an opportunistic infection
- who have resided or traveled in areas of endemic tuberculosis
or endemic mycoses; or
- with underlying conditions that may predispose them to
infection.
Closely monitor patients for infections during and after
Olumiant treatment. Interrupt Olumiant if a patient develops a
serious infection, an opportunistic infection, or sepsis. Do not
resume Olumiant until the infection is controlled.
Tuberculosis – Before initiating
Olumiant, evaluate and test patients for latent or active
infection and treat patients with latent TB with standard
antimycobacterial therapy. Olumiant should not be given to patients
with active TB. Consider anti-TB therapy prior to initiating
Olumiant in patients with a history of latent or active TB in whom
an adequate course of treatment cannot be confirmed, and for
patients with a negative test for latent TB but who have risk
factors for TB infection. Monitor patients for TB during Olumiant
treatment.
Viral Reactivation – Viral reactivation,
including cases of herpes virus reactivation (e.g., herpes zoster),
were reported in clinical studies with Olumiant. If a patient
develops herpes zoster, interrupt Olumiant treatment until the
episode resolves.
The impact of Olumiant on chronic viral hepatitis reactivation
is unknown. Screen for viral hepatitis in accordance with clinical
guidelines before initiating Olumiant.
MALIGNANCY AND LYMPHOPROLIFERATIVE
DISORDERS: Malignancies were observed in Olumiant
clinical studies. Consider the risks and benefits of Olumiant prior
to initiating therapy in patients with a known malignancy other
than a successfully treated non-melanoma skin cancer (NMSC) or when
considering continuing Olumiant in patients who develop a
malignancy. NMSCs were reported in patients treated with Olumiant.
Periodic skin examination is recommended for patients who are at
increased risk for skin cancer.
THROMBOSIS: Thrombosis, including DVT and PE,
has been observed at an increased incidence in Olumiant-treated
patients compared to placebo. In addition, arterial thrombosis
events in the extremities have been reported in clinical studies
with Olumiant. Many of these adverse events were serious and some
resulted in death. There was no clear relationship between platelet
count elevations and thrombotic events. Use Olumiant with
caution in patients who may be at increased risk of thrombosis. If
clinical features of DVT/PE or arterial thrombosis occur, evaluate
patients promptly and treat appropriately.
GASTROINTESTINAL PERFORATIONS: Gastrointestinal
perforations have been reported in Olumiant clinical studies,
although the role of JAK inhibition in these events is not known.
Use Olumiant with caution in patients who may be at increased
risk for gastrointestinal perforation (e.g., patients with a
history of diverticulitis). Promptly evaluate patients who present
with new onset abdominal symptoms for early identification of
gastrointestinal perforation.
LABORATORY ABNORMALITIES:
Neutropenia – Olumiant treatment was
associated with an increased incidence of neutropenia (absolute
neutrophil count [ANC] <1000 cells/mm3) compared
to placebo. Avoid initiation or interrupt Olumiant treatment in
patients with an ANC <1000 cells/mm3. Evaluate
at baseline and thereafter according to routine patient
management.
Lymphopenia – Absolute lymphocyte count (ALC)
<500 cells/mm3 were reported in Olumiant
clinical trials. Lymphocyte counts less than the lower limit of
normal were associated with infection in patients treated with
Olumiant, but not placebo. Avoid initiation or interrupt Olumiant
treatment in patients with an ALC
<500 cells/mm3. Evaluate at baseline and
thereafter according to routine patient management.
Anemia – Decreases in hemoglobin levels to
<8 g/dL were reported in Olumiant clinical trials. Avoid
initiation or interrupt Olumiant treatment in patients with
hemoglobin <8 g/dL. Evaluate at baseline and thereafter
according to routine patient management.
Liver Enzyme Elevations – Olumiant treatment
was associated with increased incidence of liver enzyme elevation
compared to placebo. Increases of ALT ≥5x upper limit of normal
(ULN) and increases of AST ≥10x ULN were observed in patients in
Olumiant clinical trials.
Evaluate at baseline and thereafter according to routine patient
management. Promptly investigate the cause of liver enzyme
elevation to identify potential cases of drug-induced liver injury.
If increases in ALT or AST are observed and drug-induced liver
injury is suspected, interrupt Olumiant until this diagnosis is
excluded.
Lipid Elevations – Treatment with Olumiant
was associated with increases in lipid parameters, including total
cholesterol, low-density lipoprotein cholesterol, and high-density
lipoprotein cholesterol. Assess lipid parameters approximately
12 weeks following Olumiant initiation. Manage patients
according to clinical guidelines for the management of
hyperlipidemia.
VACCINATIONS: Avoid use of live vaccines with
Olumiant. Update immunizations in agreement with current
immunization guidelines prior to initiating Olumiant
therapy.
HYPERSENSITIVITY: Reactions such as
angioedema, urticaria, and rash that may reflect drug sensitivity
have been observed in patients receiving Olumiant, including
serious reactions. If a serious hypersensitivity reaction occurs,
promptly discontinue Olumiant while evaluating the potential causes
of the reaction.
ADVERSE REACTIONS
Adverse reactions (occurring in ≥1%
of Olumiant-treated patients in placebo-controlled trials) include:
upper respiratory tract infections, headache, abdominal pain,
nausea, herpes simplex, urinary tract infection, acne, and herpes
zoster.
USE IN SPECIFIC POPULATIONS
PREGNANCY AND LACTATION: No information is available
to support the use of Olumiant in pregnancy or lactation. Advise
women not to breastfeed during treatment with Olumiant.
HEPATIC AND RENAL IMPAIRMENT: Olumiant is not
recommended in patients with severe hepatic impairment or in
patients with severe renal impairment.
Please click to access full Prescribing
Information, including Boxed Warning about Serious infections,
Malignancies, and Thrombosis, and Medication Guide.
BA HCP ISI 09JUL2020
About Atopic Dermatitis
Atopic dermatitis (AD), or
atopic eczema, is a chronic, relapsing skin disease characterized
by intense itching, dry skin and inflammation that can be present
on any part of the body.1 AD is a heterogeneous
disease both biologically and clinically, but may be characterized
by a highly variable appearance in which flares occur in an
unpredictable manner.
Moderate to severe AD is characterized by intense itching, which
leads to an itch-scratch cycle that further damages the
skin.1 Like other chronic inflammatory diseases, AD is
immune-mediated and involves a complex interplay of immune cells
and inflammatory cytokines.2
About Lilly in Dermatology
By following the science
through unchartered territory, we continue Lilly's legacy of
delivering innovative medicines that address unmet needs and have
significant impacts on people's lives around the world.
Skin-related diseases are more than skin deep. We understand the
devastating impact this can have on people's lives. At Lilly,
we are relentlessly pursuing a robust dermatology pipeline to
provide innovative, patient-centered solutions so patients with
skin-related diseases can aspire to live life without
limitations.
About Eli Lilly and Company
Lilly is a global health
care leader that unites caring with discovery to create medicines
that make life better for people around the world. We were founded
more than a century ago by a man committed to creating high-quality
medicines that meet real needs, and today we remain true to that
mission in all our work. Across the globe, Lilly employees work to
discover and bring life-changing medicines to those who need them,
improve the understanding and management of disease, and give back
to communities through philanthropy and volunteerism. To learn more
about Lilly, please visit us at lilly.com and
lilly.com/newsroom.
About Incyte
Incyte is a Wilmington, Delaware-based, global
biopharmaceutical company focused on finding solutions for serious
unmet medical needs through the discovery, development and
commercialization of proprietary therapeutics. For additional
information on Incyte, please visit Incyte.com and follow
@Incyte.
OLUMIANT® is a registered trademark owned or licensed
by Eli Lilly and Company, its subsidiaries, or affiliates.
P-LLY
This press release contains forward-looking statements (as that
term is defined in the Private Securities Litigation Reform Act of
1995) about OLUMIANT (baricitinib) as a treatment for patients with
rheumatoid arthritis and a possible treatment for patients with
atopic dermatitis and other conditions and reflects Lilly's and
Incyte's current beliefs and expectations. However, as with any
pharmaceutical product, there are substantial risks and
uncertainties in the process of research, development, and
commercialization. Among other things, there can be no guarantee
that planned or ongoing studies will be completed as planned, that
future study results will be consistent with the results to date,
and that OLUMIANT will receive additional regulatory approvals, or
be commercially successful. For further discussion of these and
other risks and uncertainties, see Lilly's and Incyte's most recent
respective Form 10-K and Form 10-Q filings with the United States
Securities and Exchange Commission. Except as required by law,
Lilly and Incyte undertake no duty to update forward-looking
statements to reflect events after the date of this release.
Refer to:
|
Marlo Scott;
scott_marlo@lilly.com; +1-317-607-8879 (Lilly media)
|
|
Kevin Hern;
hern_kevin_r@lilly.com; +1-317-277-1838 (Lilly
investors)
|
|
Catalina Loveman;
cloveman@incyte.com; +1-302-498-6171 (Incyte media)
|
|
Christine Chiou;
cchiou@incyte.com; +1-302-274-4773 (Incyte investors)
|
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