INDIANAPOLIS, Jan.
24, 2020 /PRNewswire/ -- Eli Lilly and Company (NYSE:
LLY) and Incyte (NASDAQ: INCY) announced today that baricitinib met
the primary endpoint in BREEZE-AD4, an investigational Phase 3,
randomized, placebo-controlled study evaluating the safety and
efficacy of baricitinib in combination with topical corticosteroids
(TCS) for the treatment of adult patients with moderate to
severe atopic dermatitis (AD) who were inadequate responders,
intolerant or had contraindication to treatment with cyclosporine.
The primary endpoint was defined by the proportion of patients
achieving at least a 75% or greater change from baseline in their
Eczema Area and Severity Index (EASI) at Week 16.
"There is a high need for additional treatment options for
patients living with moderate to severe AD, particularly those who
failed conventional systemic treatments like cyclosporine,"
said Lotus Mallbris, M.D., Ph.D., vice president of immunology
development at Lilly. "As we look to progress our treatment
portfolio for chronic skin conditions, the continued insights from
the development program in AD further the potential of baricitinib
to pursue this indication and to reach patients."
BREEZE-AD4 is a multicenter, double-blind, randomized,
placebo-controlled study conducted outside of the U.S. The study
evaluated the efficacy and safety of the 1-mg, 2-mg and 4-mg doses
of baricitinib in combination with TCS in patients with moderate to
severe AD who have experienced failure to cyclosporine or are
intolerant to—or have contraindication to—cyclosporine. In this
study, the 4-mg dose of baricitinib plus TCS met the primary
endpoint as defined by the proportion of participants achieving
EASI75 at Week 16.
All arms in
combination with TCS
|
Placebo
(n=93)
|
Baricitinib 1-mg
(n=93)
|
Baricitinib 2-mg
(n=185)
|
Baricitinib 4-mg
(n=92)
|
EASI75 at Week 16, n
(%)
|
16 (17.2)
|
21
(22.6) ǂ
|
51
(27.6) ǂ
|
29 (31.5)*
|
vIGAa of 0
or 1 at Week 16, n (%)
|
9 (9.7)
|
12
(12.9) ǂ
|
28
(15.1) ǂ
|
20 (21.7)*
|
4-point improvement
in Itch NRS at Week 16, n (%)
|
7 (8.2)
|
18 (23.1)*
|
38
(22.9)**
|
29
(38.2)***
|
ǂ P n.s. * P
≤ 0.05, ** P≤0.01, and *** P≤0.001 for baricitinib compared to
placebo by analysis unadjusted for multiplicity. Non-responder
imputation upon rescue with high/very high potency TCS.
avIGA = validated Investigator's Global
Assessment
|
The safety profile was consistent with the known safety findings
of baricitinib in AD. The most common treatment-emergent adverse
events (TEAEs) included nasopharyngitis, headache, and influenza.
No venous thromboembolic events (VTEs) or deaths were reported in
the trial.
Lilly recently submitted baricitinib for regulatory review in
Europe as a treatment for patients
with moderate to severe atopic dermatitis and plans to submit for
approval in the U.S. and Japan in
2020. Full results from the BREEZE-AD4 study will be disclosed at
future scientific venues and in peer-reviewed journals.
Baricitinib is approved for the treatment of adults with
moderately to severely active rheumatoid arthritis (RA) in more
than 60 countries, including the U.S., member states of the EU and
Japan, and is marketed as
OLUMIANT®.
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. Treatment for latent
infection should be considered 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 local 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 to ≥5x and ≥10x upper limit of
normal were observed for both ALT and AST 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.
ADVERSE REACTIONS
Adverse reactions (≥1%) include: upper respiratory tract
infections (16.3%, 14.7%, 11.7%), nausea (2.7%, 2.8%, 1.6%), herpes
simplex (0.8%, 1.8%, 0.7%) and herpes zoster (1.0%, 1.4%, 0.4%) for
Olumiant 2 mg, baricitinib 4 mg, and placebo, respectively.
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 11OCT2019
About BREEZE-AD4
BREEZE-AD4 is a long-term,
multicenter, double-blind, randomized, placebo-controlled, Phase 3
study in adult patients with moderate to severe atopic dermatitis
(AD). BREEZE-AD4, conducted outside of the U.S., evaluated the
efficacy and safety of the 1-mg, 2-mg and 4-mg doses of baricitinib
in combination with topical corticosteroids in participants with
moderate to severe AD who have experienced failure to cyclosporine
or are intolerant to—or have contraindication to—cyclosporine. The
primary endpoint was defined by the proportion of participants
achieving Eczema Area and Severity Index 75 (EASI75) at Week 16.
BREEZE-AD1, -AD2 and -AD7 results were disclosed in 2019.
About OLUMIANT®
OLUMIANT is a once-daily,
oral JAK inhibitor approved in the U.S. for the treatment of adults
with moderately to severely active rheumatoid arthritis who have
had an inadequate response to one or more TNF inhibitor therapies,
and approved outside of the U.S. for patients with moderately to
severely active rheumatoid arthritis who have had an inadequate
response to one or more DMARDs.1 There are four known
JAK enzymes: JAK1, JAK2, JAK3 and TYK2. JAK-dependent cytokines
have been implicated in the pathogenesis of a number of
inflammatory and autoimmune diseases.2 OLUMIANT has
greater inhibitory potency at JAK1, JAK2 and TYK2 relative to JAK3;
however, the relevance of inhibition of specific JAK enzymes to
therapeutic effectiveness is not currently
known.1 OLUMIANT is approved in more than 60
countries.
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.3 AD is a
heterogeneous disease both clinically and biologically, but may be
characterized by chronic baseline symptoms of itch, redness and
skin damage that are often punctuated with episodic, sometimes
unpredictable, flares or exacerbations.4,5 AD
affects approximately 1-3% of adults worldwide.6
Moderate to severe AD is characterized by intense itching,
resulting in visibly damaged skin.7 Like other
chronic inflammatory diseases, AD is immune-mediated and involves a
complex interplay of immune cells and inflammatory
cytokines.8
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 healthcare 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 www.lilly.com and newsroom.lilly.com/social-channels. P-LLY
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.
This press release also 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 as a potential treatment for
patients with moderate- to severe atopic dermatitis, and reflects
Lilly's and Incyte's current beliefs. However, as with any
pharmaceutical product, there are substantial risks and
uncertainties in the process of development and commercialization.
Among other things, there can be no guarantee 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.
1Olumiant Prescribing Information, 2019.
2Walker JG and Smith MD. J Rheumatol.
2005;32;1650-1653.
3Zuberbier T, Orlow SJ, Paller AS, et al. Patient
perspectives on the management of atopic dermatitis. The Journal of
Allergy and Clinical Immunology. 2006;118: 226-32.
4Thijs JL, Strickland I, Bruijnzeel-Koomen C, et. al.
Moving toward endotypes in atopic dermatitis: identification of
patient clusters based on serum biomarker analysis. The Journal of
Allergy and Clinical Immunology. 2017.
5Langan SM, Thomas KS,
Williams HC. What is meant by "flare" in atopic dermatitis? A
systematic review and proposal. Arch Dermatol.
2006;142:1190-1196.
6Nutten S. Atopic dermatitis: global epidemiology and
risk factors. Annals of Nutrition and Metabolism. 2015;66(suppl 1):
8-16.
7Yosipovitch G, Papoiu AD. What causes itch in atopic
dermatitis? Current Allergy and Asthma Reports.
2008;8:306-311.
8Weidinger, S, Novak, N. Atopic dermatitis. The Lancet
Volume 387. 2016;10023:1109-1122.
Refer
to:
|
Kristen Basu;
basu_kristen_porter@lilly.com; +1-317-447-2199 (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)
|
|
Michael Booth, DPhil;
mbooth@incyte.com; +1-302-498-5914 (Incyte investors)
|
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