INDIANAPOLIS, Sept. 14, 2017 /PRNewswire/ -- Eli Lilly and
Company (NYSE: LLY) and Incyte Corporation (NASDAQ: INCY) today
announced new safety and efficacy data from a Phase 2 study of
baricitinib in people with moderate-to-severe atopic dermatitis
(AD). The results showed that baricitinib in combination with a
mid-potency topical corticosteroid (TCS) significantly improved the
signs and symptoms of AD compared to TCS alone. The results were
presented in an oral presentation today at the European Academy of
Dermatology and Venereology (EADV) Annual Meeting in Geneva, Switzerland.
"Atopic dermatitis has a significant impact on the quality of
life, including the emotional and social wellbeing of people with
the disease," said James McGill,
M.D., distinguished medical fellow and global brand development
leader, Lilly Bio-Medicines. "Baricitinib demonstrated clinical
efficacy in a Phase 2 study in atopic dermatitis. The study was
designed to understand the safety and efficacy of baricitinib in
patients refractory to topical steroids. In this population,
baricitinib was able to achieve improvement in both itch and skin
inflammation. Based on these data, we plan to initiate a Phase 3
clinical program for atopic dermatitis later this year."
After 16 weeks of treatment, 61 percent of patients treated with
4-mg of baricitinib in combination with TCS (n=38) achieved a 50
percent or greater reduction in their overall disease severity as
measured by the Eczema Area and Severity Index (EASI-50), compared
to 37 percent of patients treated with TCS alone (n=49),
(p<0.05). Among patients treated with 2-mg of baricitinib in
combination with TCS (n=37), 57 percent achieved EASI-50, although
these results were not statistically different compared to
treatment with TCS alone (p=0.065). At four weeks, 68 percent of
patients treated with 4-mg baricitinib in combination with TCS and
62 percent of patients treated with 2-mg of baricitinib in
combination with TCS achieved EASI-50, compared to 16 percent of
patients treated with TCS alone (p<0.001).
"Importantly, in this study, patients had to fail four weeks of
supervised therapy with a mid-potency topical corticosteroid before
randomization, selecting for a difficult to treat patient
population," said Emma
Guttman-Yassky, M.D., Ph.D., Sol and Clara Kest professor of
dermatology, vice chair Department of Dermatology, director of the
Center for Excellence in Eczema and director of the Laboratory of
Inflammatory Skin Diseases in the Department of Dermatology at
Icahn School of Medicine at Mount Sinai Medical Center in
New York. "These new results
suggest that baricitinib may have the potential to become an oral
treatment option for patients suffering from atopic dermatitis who
are unable to achieve adequate control with TCS."
During the treatment period, treatment-emergent adverse events
(TEAE) occurred in 49 percent of patients treated with TCS, 46
percent and 71 percent of the 2-mg and 4-mg baricitinib in
combination with TCS groups, respectively. The most common TEAEs in
the 4-mg baricitinib in combination with TCS group were upper
respiratory tract infections and nasopharyngitis, headache, and
increases in asymptomatic laboratory changes, namely increases in
creatine phosphokinase (CPK).
INDICATIONS AND USAGE FOR OLUMIANT
Therapeutic
Indications
Baricitinib was approved in February 2017 for the treatment of adults with
moderate-to-severe-active rheumatoid arthritis in the European
Union and is marketed as Olumiant
IMPORTANT SAFETY INFORMATION FOR OLUMIANT BASED ON THE EU
APPROVED SUMMARY OF PRODUCT CHARACTERISTICS
CONTRAINDICATIONS
Hypersensitivity to the active
substance or to any of the excipients.
Pregnancy.
SPECIAL WARNINGS AND PRECAUTIONS FOR USE
Infections
Baricitinib is associated with an
increased rate of infections such as upper respiratory tract
infections compared to placebo. In treatment naïve patients,
combination with methotrexate resulted in increased frequency of
infections compared to baricitinib monotherapy. The risks and
benefits of treatment with Olumiant should be carefully considered
prior to initiating therapy in patients with active, chronic or
recurrent infections. If an infection develops, the patient should
be monitored carefully and Olumiant therapy should be temporarily
interrupted if the patient is not responding to standard therapy.
Olumiant treatment should not be resumed until the infection
resolves.
Tuberculosis
Patients should be screened for
tuberculosis (TB) before starting Olumiant therapy. Olumiant should
not be given to patients with active TB. Anti-TB therapy should be
considered prior to initiation of Olumiant in patients with
previously untreated latent TB.
Haematological Abnormalities
Absolute Neutrophil Count (ANC) < 1 x 109 cells/L,
Absolute Lymphocyte Count (ALC) < 0.5 x 109 cells/L
and haemoglobin < 8 g/dL were reported in less than 1% of
patients in clinical trials. Treatment should not be initiated, or
should be temporarily interrupted, in patients with an ANC < 1 x
109 cells/L, ALC < 0.5 x 109 cells/L or
haemoglobin < 8 g/dL observed during routine patient
management.
The risk of lymphocytosis is increased in elderly patients with
rheumatoid arthritis. Rare cases of lymphoproliferative disorders
have been reported.
Viral Reactivation
Viral reactivation, including
cases of herpes virus reactivation (e.g., herpes zoster, herpes
simplex), were reported in clinical studies. Herpes zoster was
reported more commonly in patients ≥ 65 years of age who had
previously been treated with both biologic and conventional DMARDs.
If a patient develops herpes zoster, Olumiant treatment should be
temporarily interrupted until the episode resolves.
Screening for viral hepatitis should be performed in accordance
with clinical guidelines before starting therapy with Olumiant.
Patients with evidence of active hepatitis B or C infection were
excluded from clinical trials. Patients, who were positive for
hepatitis C antibody but negative for hepatitis C virus RNA, were
allowed to participate. Patients with hepatitis B surface antibody
and hepatitis B core antibody, without hepatitis B surface antigen,
were also allowed to participate; such patients should be monitored
for expression of hepatitis B virus (HBV) DNA. If HBV DNA is
detected, a liver specialist should be consulted to determine if
treatment interruption is warranted.
Vaccination
No data are available on the response to
vaccination with live or inactivated vaccines in patients receiving
baricitinib. Use with live, attenuated vaccines during, or
immediately prior to, Olumiant therapy is not recommended.
International treatment guidelines on vaccination in rheumatoid
arthritis patients should be followed when varicella zoster
vaccination is considered prior to treatment with Olumiant.
Lipids
Dose dependent increases in blood lipid
parameters were reported in patients treated with baricitinib
compared to placebo. Elevations in LDL cholesterol decreased to
pre-treatment levels in response to statin therapy. Lipid
parameters should be assessed approximately 12 weeks following
initiation of Olumiant therapy and thereafter patients should be
managed according to international clinical guidelines for
hyperlipidaemia. The effect of these lipid parameter elevations on
cardiovascular morbidity and mortality has not been determined.
Hepatic transaminase elevations
Increases in alanine
transaminase (ALT) and aspartate transaminase (AST) to ≥ 5 and ≥ 10
x upper limit of normal (ULN) were reported in less than 1% of
patients in clinical trials. In treatment-naïve patients,
combination with methotrexate resulted in increased frequency of
hepatic transaminase elevations compared with baricitinib
monotherapy. If increases in ALT or AST are observed during routine
patient management and drug-induced liver injury is suspected,
Olumiant should be temporarily interrupted until this diagnosis is
excluded.
Malignancy
The risk of malignancies including
lymphoma is increased in patients with rheumatoid arthritis.
Immunomodulatory medicinal products may increase the risk of
malignancies including lymphoma. The clinical data are insufficient
to assess the potential incidence of malignancies following
exposure to baricitinib. Long-term safety evaluations are
ongoing.
Venous Thromboembolism
Events of deep venous
thrombosis (DVT) and pulmonary embolism (PE) have been reported in
patients receiving baricitinib. Olumiant should be used with
caution in patients with risk factors for DVT/PE, such as older
age, obesity, a medical history of DVT/PE, or patients undergoing
surgery and immobilisation. If clinical features of DVT/PE occur,
Olumiant treatment should be temporarily interrupted and patients
should be evaluated promptly, followed by appropriate
treatment.
Laboratory Monitoring
Please refer to the SmPC for
laboratory measures and monitoring guidance.
Immunosuppressive Medicinal Products
Combination with biologic DMARDs or other Janus kinase (JAK)
inhibitors is not recommended, as a risk of additive
immunosuppression cannot be excluded. Data concerning use of
baricitinib with potent immunosuppressive medicinal products (e.g.,
azathioprine, tacrolimus, ciclosporin) are limited and caution
should be exercised when using such combinations.
ADVERSE REACTIONS
Undesirable Effects: Summary of
Safety Profile
The most commonly reported adverse drug
reactions (ADRs) occurring in ≥ 2% of patients treated with
Olumiant monotherapy or in combination with conventional synthetic
DMARDs were increased LDL cholesterol (33.6%), upper respiratory
tract infections (14.7%) and nausea (2.8%). Infections reported
with Olumiant treatment included Herpes zoster.
Please see Summary of Product
Characteristics for additional information.
About Baricitinib
Baricitinib is a once-daily oral
JAK inhibitor currently in clinical studies for inflammatory and
autoimmune diseases. 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,
suggesting that JAK inhibitors may be useful for the treatment of a
broad range of inflammatory conditions, including rheumatoid
arthritis.
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. Baricitinib was submitted for regulatory
review seeking marketing approval for the treatment of rheumatoid
arthritis in the U.S., the European Union and Japan in 2016. Baricitinib was approved in the
EU in February 2017 and in
Japan in July 2017. In April
2017, the U.S. Food and Drug Administration issued a
Complete Response Letter on the New Drug Application for
baricitinib. Baricitinib remains under review in other markets. It
is also being studied for the treatment of atopic dermatitis and
systemic lupus erythematosus. The Phase 3 program for psoriatic
arthritis is expected to begin in 2018.
About Atopic Dermatitis
Atopic dermatitis (AD), a
serious form of 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 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.2,3 AD affects
approximately 1-3 percent of adults worldwide.4
Moderate-to-severe AD is characterized by intense itching,
resulting in visibly damaged skin, sleep loss and a significant
impact on patients' quality of life. AD patients often experience
anxiety, depression and reduced self-esteem.5 Like other
chronic inflammatory diseases, AD is immune-mediated and involves a
complex interplay of immune cells and inflammatory
cytokines.6
About the Baricitinib Phase 2 Clinical Trial in Atopic
Dermatitis
The safety and efficacy of baricitinib in
patients with moderate-to-severe AD was evaluated in a Phase 2
randomized, double-blind, placebo-controlled study over 16 weeks
(NCT02576938). In the trial, 124 patients were randomized 4:3:3 to
placebo or baricitinib 2-mg or 4-mg once daily dose. All patients
received background Triamcinolone 0.1% cream for four weeks prior
to randomization, and throughout the trial as indicated by the
product label and the treating physician. The primary objective of
the study was the proportion of patients achieving a ≥50%
improvement in EASI scores (EASI-50). The study also compared the
SCORing Atopic Dermatitis (SCORAD) score and EASI total score
percent change from baseline (CFB) between groups. Patient-reported
outcomes (PROs) assessed at each visit included Dermatology Life
Quality Index (DLQI), Itch Numeric Rating Scale (NRS) and Patient
Oriented Eczema Measure (POEM).
About Incyte
Incyte Corporation is a Wilmington, Delaware-based biopharmaceutical
company focused on the discovery, development and commercialization
of proprietary therapeutics. For additional information on Incyte,
please visit the Company's web site at www.incyte.com.
Follow @Incyte on Twitter at https://twitter.com/Incyte.
About Eli Lilly and Company
Lilly is a global
healthcare leader that unites caring with discovery to 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
This press release contains forward-looking statements (as that
term is defined in the Private Securities Litigation Reform Act of
1995) about baricitinib as a potential treatment for patients with
atopic dermatitis, and reflects Lilly's
and Incyte's current belief. 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 future study results will be
consistent with the results to date or that baricitinib 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 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.
1 Zuberbier 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.
2 Thijs 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.
3 Langan SM, Thomas KS,
Williams HC. What is meant by "flare" in atopic dermatitis? A
systematic review and proposal. Arch Dermatol.
2006;142:1190-1196.
4 Nutten S. Atopic dermatitis: global epidemiology and
risk factors. Annals of Nutrition and Metabolism.
2015;66(suppl 1): 8-16.
5 Yosipovitch G, Papoiu AD. What causes itch in atopic
dermatitis? Current Allergy and Asthma Reports.
2008;8:306-311.
6 Weidinger, S, Novak, N. Atopic dermatitis. The
Lancet Volume 387. 2016;10023:1109-1122.
Refer to:
|
Danielle Neveles;
danielle.neveles@lilly.com; +1-317-796-4564 (Lilly
media)
|
|
Phil Johnson;
johnson_philip_l@lilly.com; +1-317-655-6874 (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)
|
View original content with
multimedia:http://www.prnewswire.com/news-releases/baricitinib-meets-primary-endpoint-in-phase-2-study-of-patients-with-moderate-to-severe-atopic-dermatitis-300518896.html
SOURCE Eli Lilly and Company; Incyte Corporation