INDIANAPOLIS, Jan. 28, 2022 /PRNewswire/ -- Eli Lilly and
Company (NYSE: LLY) and Incyte (NASDAQ:INCY) today announced
updates on the Phase 3 development program
for OLUMIANT® (baricitinib) in adults with active
systemic lupus erythematosus (also referred to as SLE and lupus)
and the status of the U.S. atopic dermatitis supplemental new drug
application (sNDA).
Lupus program update
Based on top-line efficacy results from two pivotal Phase 3 trials
(SLE-BRAVE-I and II), Lilly has decided to discontinue the Phase 3
development program for OLUMIANT in lupus.
In SLE-BRAVE-I, the baricitinib 4-mg oral dose met the primary
endpoint, demonstrating a statistically significant reduction in
disease activity as measured by the proportion of adults with
active lupus who achieved an SRI-4 response (a composite
measurement of overall disease activity) at Week 52 compared to
placebo. The SLE-BRAVE-II study, which also studied adults with
active lupus, did not meet the primary endpoint of SRI-4 response.
Key secondary endpoints were not met in either
study. Safety findings from both lupus studies were consistent
with previously published OLUMIANT data and did not impact our
decision to discontinue the program. Lilly intends to analyze the
totality of our lupus data to help inform our understanding of the
disease and advance the science and intends to publish findings at
a later date.
Lilly is working with investigators to appropriately conclude
the Phase 3 SLE long-term extension trial, SLE-BRAVE-X, which was
designed to evaluate the long-term safety and efficacy of OLUMIANT
over three years in adults who completed SLE-BRAVE-I or
II.
Atopic dermatitis regulatory update
Lilly is in ongoing discussion with the U.S. Food and Drug
Administration (FDA) regarding the status of the sNDA for OLUMIANT
for the treatment of adults with moderate-to-severe atopic
dermatitis. At this point, the company does not have alignment with
the FDA on the indicated population. Given the Agency's
position, there is a possibility that this could lead to a Complete
Response Letter (CRL). The efficacy and safety profile of OLUMIANT
was evaluated in eight atopic dermatitis clinical trials (six
double-blind, randomized, placebo-controlled studies and two
long-term extension studies) inclusive of patients whose disease is
not adequately controlled with topical prescription therapies or
when those therapies are not advisable. The safety profile in these
trials was consistent with previously published OLUMIANT data.
OLUMIANT was the first JAK inhibitor approved to treat
moderate-to-severe patients with atopic dermatitis who
have an inadequate response to topical treatments in the European
Union and Japan.
"On behalf of all of us at Lilly, we thank the participants,
trial sites and clinical investigators for their essential
contributions to the OLUMIANT atopic dermatitis and lupus programs.
We are disappointed for the millions of people who suffer from
these complex and hard-to-treat autoimmune diseases and are in need
of more treatment options, and we remain committed to pursuing
treatment advances in immunology that can make life better for
people around the world," said Lotus Mallbris, M.D., Ph.D.,
vice president of global immunology development and medical affairs
at Lilly. "These decisions do not affect Lilly's other research
efforts for OLUMIANT or its approved indications. We are confident
in OLUMIANT for approved indications in the U.S. and globally as
OLUMIANT has one of the largest and longest sets of available
safety data in the JAK inhibitor class, including nine years across
the clinical development program."
"This year, we are eager to provide OLUMIANT to more patients in
therapeutic areas where there is significant unmet medical need,"
Mallbris said. "We look forward to potential regulatory approvals
for OLUMIANT in 2022, including COVID-19 for certain hospitalized
patients in the U.S. and severe alopecia areata in the U.S.,
European Union and Japan, where
OLUMIANT has the potential to be a first-in-disease treatment."
More than 325,000 people worldwide have been treated with
OLUMIANT to date across approved indications. On January 13, 2022, the World Health Organization
(WHO) released new guidelines on treatments for COVID-19, strongly
recommending the use of baricitinib in combination with
corticosteroids for severely or critically ill patients. To read
Lilly's statement about the WHO COVID-19 guidelines update, click
here. Baricitinib is approved or authorized for emergency use for
treatment of certain hospitalized patients with COVID-19 in 14
countries. To date, more than 740,000 patients globally are
estimated to have been treated with baricitinib for COVID-19. In
the U.S., baricitinib is authorized by the FDA for emergency use in
hospitalized adults and pediatric patients two years of age or
older requiring supplemental oxygen, noninvasive or invasive
mechanical ventilation, or extracorporeal membrane oxygenation
(ECMO). The FDA has granted priority review for the sNDA for
baricitinib for the treatment of certain hospitalized patients with
COVID-19, with an anticipated regulatory action in Q2 2022.
Authorized Use Under the EUA and Important Safety Information
for baricitinib (in the United
States) for COVID-19
Baricitinib is authorized for use under an Emergency Use
Authorization (EUA) for treatment of COVID-19 in hospitalized
adults and pediatric patients 2 years of age or older requiring
supplemental oxygen, non-invasive or invasive mechanical
ventilation, or ECMO.
Baricitinib has not been approved for the treatment of COVID-19,
but has been authorized for emergency use by the FDA. Baricitinib
is authorized under an EUA only for the duration of the declaration
that circumstances exist justifying the authorization of the EUA of
baricitinib under Section 564(b)(1) of the Act, 21 U.S.C. §
360bbb-3(b)(1), unless the declaration is terminated or
authorization revoked sooner.
For more information about the authorized use of baricitinib in
COVID-19 and mandatory requirements of the EUA, please see the FDA
Letter of Authorization, Fact Sheet for Healthcare Providers and
Fact Sheet for Patients, Parents and Caregivers (English)
(Spanish).
Important Safety Information about baricitinib for
COVID-19
The following provides essential safety
information on the unapproved use of baricitinib under the
Emergency Use Authorization.
Warnings
Serious Infections: There is limited information
regarding use of baricitinib in patients with COVID-19 and
concomitant active serious infections.
Serious infections have occurred in patients receiving
baricitinib. Avoid the use of baricitinib with known active
tuberculosis. Consider if the potential benefits outweigh the
potential risks of baricitinib treatment in patients with active
serious infections other than COVID-19 or chronic/recurrent
infections.
Thrombosis: In hospitalized patients with COVID-19,
prophylaxis for venous thromboembolism is recommended unless
contraindicated. If clinical features of deep vein thrombosis or
pulmonary embolism occur, patients should be evaluated promptly and
treated appropriately.
Abnormal Laboratory Values: There is limited
information regarding use of baricitinib in patients with COVID-19
and any of the following clinical findings: absolute neutrophil
count (ANC) <1000 cells/mm3, absolute lymphocyte
count (ALC) <200 cells/mm3, and hemoglobin
<8g/dL.
Evaluate estimated glomerular filtration rate (eGFR), liver
enzymes, and complete blood count at baseline and thereafter
according to local patient management practice. Monitor closely
when treating patients with abnormal baseline and post-baseline
laboratory values. Follow dose adjustments as recommended in the
Fact Sheet for Healthcare Providers for patients with abnormal
renal, hematological and hepatic laboratory values. Manage patients
according to routine clinical guidelines.
Vaccinations: Avoid use of live vaccines with
baricitinib.
Hypersensitivity: If a serious hypersensitivity
occurs, discontinue baricitinib while evaluating the potential
causes of the reaction.
See Warnings and Precautions in the FDA-approved full
Prescribing Information and Medication Guide for additional
information on risks associated with longer-term treatment with
baricitinib.
Serious Side Effects
Serious venous thrombosis, including pulmonary embolism, and
serious infections have been observed in COVID-19 patients treated
with baricitinib and are known adverse drug reactions of
baricitinib.
Adverse Reactions
In the COVID-19 clinical trials, adverse drug reactions in the
safety population occurring in ≥ 1% of patients treated with
baricitinib were alanine aminotransferase (ALT) ≥3 x upper limit of
normal (ULN) (18.0%), aspartate aminotransferase (AST) ≥3 x ULN
(11.5%), thrombocytosis >600,000 cells/mm3 (8.2%),
creatine phosphokinase (CPK) >5 x ULN (3.7%), neutropenia
<1000 cells/mm3 (2.2%), deep vein thrombosis (1.5%),
pulmonary embolism (1.4%), and urinary tract infection (1.3%).
Use in Specific Populations
Pregnancy: Baricitinib should be used during pregnancy
only if the potential benefit justifies the potential risk for the
mother and the fetus.
Renal Impairment: There are limited data for
baricitinib in patients with severe renal impairment. Baricitinib
is not recommended for patients who are on dialysis, have end-stage
renal disease, or have acute kidney injury.
Hepatic Impairment: Baricitinib has not been studied
in patients with severe hepatic impairment. Baricitinib should only
be used in patients with severe hepatic impairment if the potential
benefit outweighs the potential risk.
Please see Fact Sheet for Healthcare Providers and Fact Sheet
for Patients, Parents and Caregivers (English) or Fact Sheet for
Patients, Parents and Caregivers (Spanish).
BC HCP EUA ISI 28JUL2021
About SLE-BRAVE-I and II Studies
SLE-BRAVE-I and II were global, double-blind,
multicenter studies evaluating the efficacy and safety of
baricitinib 2-mg and 4-mg oral once-daily compared to placebo in
adults with active lupus. The predefined primary endpoint for the
studies was the proportion of participants achieving an SRI-4
response at Week 52. The SRI-4 response is a composite clinical
endpoint used in lupus trials to measure response to treatment
based on decrease in overall disease activity. More than 1,500
adults with active lupus were enrolled across studies, with all
patients in the baricitinib and placebo treatment groups receiving
standard of care background therapy.
About OLUMIANT®
OLUMIANT, a once-daily, oral JAK inhibitor was discovered by
Incyte and licensed to Lilly. It is approved in the U.S. and more
than 75 countries as a treatment for adults with moderate to severe
rheumatoid arthritis and is approved in more than 50 countries,
including the European Union and Japan, for the treatment of adult patients
with moderate to severe atopic dermatitis who are candidates for
systemic therapy. To date, more than 325,000 patients have been
treated with OLUMIANT worldwide across approved indications.
Marketing authorization for the treatment of hospitalized patients
with COVID-19 has been granted for OLUMIANT in multiple countries.
The U.S. FDA-approved labeling for OLUMIANT includes a Boxed
Warning for Serious Infections, Mortality, Malignancy, Major
Adverse Cardiovascular Events, and Thrombosis. See the full
Prescribing Information here. OLUMIANT is also being investigated
in alopecia areata (AA) and juvenile idiopathic arthritis
(JIA).
In December 2009, Lilly and Incyte
announced an exclusive worldwide license and collaboration
agreement for the development and commercialization of OLUMIANT 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) blockers. Limitation of Use: Not
recommended for use in combination with other JAK inhibitors,
biologic disease-modifying antirheumatic drugs (DMARDs), or with
potent immunosuppressants such as azathioprine and
cyclosporine.
IMPORTANT SAFETY INFORMATION FOR OLUMIANT (baricitinib)
tablets
WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR
ADVERSE CARDIOVASCULAR EVENTS, 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.
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 use of 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.
Consider anti-TB therapy prior to initiation of 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.
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.
MORTALITY
In a large, randomized, postmarketing
safety study in rheumatoid arthritis (RA) patients 50 years of age
and older with at least one cardiovascular risk factor comparing
another Janus kinase (JAK) inhibitor to tumor necrosis factor (TNF)
blockers, a higher rate of all-cause mortality, including sudden
cardiovascular death, was observed with the JAK inhibitor.
Consider the benefits and risks for the individual patient prior
to initiating or continuing therapy with Olumiant.
MALIGNANCIES
Lymphoma and other malignancies have
been observed in patients treated with Olumiant. In RA patients
treated with another JAK inhibitor, a higher rate of malignancies
(excluding non-melanoma skin cancer [NMSC]) was observed when
compared with TNF blockers. Patients who are current or past
smokers are at additional increased risk. A higher rate of
lymphomas was observed in patients treated with the JAK inhibitor
compared to those treated with TNF blockers. A higher rate of lung
cancers and an additional increased risk of overall malignancies
were observed in current or past smokers treated with the JAK
inhibitor compared to those treated with TNF blockers.
Consider the benefits and risks for the individual patient prior
to initiating or continuing therapy with Olumiant, particularly in
patients with a known malignancy (other than successfully treated
NMSC), patients who develop a malignancy, and patients who are
current or past smokers.
NMSCs have been reported in patients treated with Olumiant.
Periodic skin examination is recommended for patients who are at
increased risk for skin cancer.
MAJOR ADVERSE CARDIOVASCULAR EVENTS
In RA patients
50 years of age and older with at least one cardiovascular risk
factor treated with another JAK inhibitor, a higher rate of major
adverse cardiovascular events (MACE) (defined as cardiovascular
death, myocardial infarction [MI], and stroke) was observed when
compared with TNF blockers. Patients who are current or past
smokers are at additional increased risk. Discontinue Olumiant in
patients that have experienced a myocardial infarction or
stroke.
Consider the benefits and risks for the individual patient prior
to initiating or continuing therapy with Olumiant, particularly in
patients who are current or past smokers and patients with other
cardiovascular risk factors. Inform patients about the symptoms of
serious cardiovascular events and the steps to take if they
occur.
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. In RA patients 50 years of age and older with at least one
cardiovascular risk factor treated with another JAK inhibitor, a
higher rate of thrombosis was observed when compared with TNF
blockers. Avoid Olumiant in patients at risk. Discontinue Olumiant
and promptly evaluate patients with symptoms of thrombosis.
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
Most common adverse reactions
include: upper respiratory tract infections (16.3%, 11.7%), nausea
(2.7%, 1.6%), herpes simplex (0.8%, 0.7%), and herpes zoster (1.0%,
0.4%) for Olumiant 2-mg and placebo, respectively.
PREGNANCY AND LACTATION
Limited data on Olumiant use
in pregnant women are not sufficient to inform a drug-associated
risk for major birth defects or miscarriage. Advise women not to
breastfeed during treatment with Olumiant.
HEPATIC AND RENAL IMPAIRMENT
Olumiant is not
recommended in patients with severe hepatic or severe renal
impairment.
Please click to access full Prescribing
Information, including Boxed Warning about Serious
Infections, Mortality, Malignancy, Major Adverse Cardiovascular
Events, and Thrombosis, and Medication Guide.
BA HCP ISI 06DEC2021
About Lilly in Immunology
Lilly is bringing our
heritage of championing groundbreaking, novel science to immunology
and is driven to change what's possible for people living with
autoimmune diseases. There are still significant unmet needs, as
well as personal and societal costs, for people living with a
variety of autoimmune diseases and our goal is to minimize the
burden of disease. Lilly is investing in leading-edge clinical
approaches across its immunology portfolio in hopes of transforming
the autoimmune disease treatment experience. We've built a deep
pipeline and are focused on advancing cutting edge science to find
new treatments that offer meaningful improvements to support the
people and the communities we serve.
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
Lilly Forward-Looking Statement
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 other approved indications and potential
treatment for patients with systematic lupus erythematosus 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
drug 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; +1-317-407-8879
(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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