INDIANAPOLIS, June 16, 2017 /PRNewswire/ -- Eli Lilly and
Company (NYSE: LLY) and Incyte Corporation (NASDAQ: INCY) today
announced a new pooled analysis of data from eight
Olumiant® (baricitinib) clinical trials, showing that
baricitinib-treated and placebo-treated patients with
moderate-to-severe rheumatoid arthritis (RA) had similar rates of
serious infection incidents. Additionally, new data from the
long-term extension (LTE) of Phase 3 trials showed that two years
of baricitinib treatment significantly lowered the rate of joint
damage progression and maintained an overall low disease activity
(LDA) throughout the treatment period in these patients. These
results were presented at an oral presentation and two poster
presentations at the Annual European Congress of Rheumatology
(EULAR 2017) in Madrid.
"We are pleased to present these data, which support the
evidence that baricitinib may be a potential long-term, oral
treatment option for people with moderate-to-severe RA, many of
whom are not achieving treatment goals with existing therapies,"
said James McGill, M.D.,
distinguished medical fellow and global brand development leader,
Lilly Bio-Medicines. "We are hopeful that baricitinib may help to
meet the needs of healthcare providers and their patients with RA
as they work toward achieving overall treatment goals."
Pooled infection data from 8 clinical trials
A pooled analysis of data from eight completed baricitinib
clinical trials (four Phase 3, three Phase 2, one Phase 1) and one
LTE study showed that there were similar incidence rates (IR) of
severe infection events between the baricitinib and placebo
groups.
- Specifically, during the first 24 weeks of treatment, in six
trials, incidence rates of serious infections in the baricitinib (4
mg) and placebo groups were 3.8 and 4.2 per 100 patient-years
(IR/100 PY), respectively. Additionally, the study also showed that
in a set of four clinical trials, IRs of serious infections per 100
PY in the 2 mg and 4 mg groups were 4.2 and 5.7, respectively,
compared to 5.1 in the placebo group in this set.
- The study also identified that concomitant corticosteroids use,
prior biologics use, non-normal BMI, Asian region of enrollment,
and advancing age are the key risk factors for serious
infections.
"Rheumatoid arthritis is a chronic disease that is often
associated with serious infections," said Kevin L. Winthrop, M.D., M.P.H., assistant
professor at Oregon Health and Science University. "These results
suggest that baricitinib treatment may not increase the incidence
of serious infections in patients with moderate-to-severe
rheumatoid arthritis compared to placebo."
Efficacy data from long-term extension study
Two presentations from a LTE study of baricitinib in
moderate-to-severe RA patients showed the continued efficacy and
long-term benefit with two years of treatment.
- Specifically, one of the analyses showed that at two years,
progression of structural joint damage, measured by change in the
van der Heijde modified total sharp score (mTSS), was significantly
lower in patients treated with baricitinib throughout the two-year
period compared to those who were first treated with placebo or
methotrexate before switching to baricitinib.
- A second analysis of up to two years in a long-term extension
study showed that among patients treated with baricitinib for up to
three years, the proportion of patients with low disease activity
(LDA) at 24 weeks in different treatment groups across trials
remained similar or increased up to three years. Additionally, the
results also showed that most patients who had responded to
treatment before entering the long-term extension study maintained
their response throughout the two-year extension period.
-
- In this study, achieving a Simplified Disease Activity Index
(SDAI) score ≤11 was considered as LDA.
"These data suggest the potential of baricitinib as an option to
control the progression of joint damage and overall disease
activity, which is important because long-term control is a key
goal in chronic inflammatory diseases like rheumatoid arthritis,"
said Steven Stein, M.D., chief
medical officer, Incyte Corporation.
Baricitinib was approved in February
2017 for the treatment of adults with moderate-to-severe RA
in the European Union and is marketed as Olumiant®.
INDICATIONS AND USAGE FOR OLUMIANT
Therapeutic indications
Olumiant is indicated for the
treatment of moderate to severe active rheumatoid arthritis in
adult patients who have responded inadequately to, or who are
intolerant to one or more disease-modifying anti-rheumatic drugs.
Olumiant may be used as monotherapy or in combination with
methotrexate.
IMPORTANT SAFETY INFORMATION FOR OLUMIANT
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.
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.
About Olumiant
Olumiant® (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., European Union and Japan in 2016, and was approved in the EU in
February 2017.
About Rheumatoid Arthritis
Rheumatoid arthritis (RA)
is an autoimmune disease characterized by inflammation and
progressive destruction of joints. More than 23 million people
worldwide suffer from RA.i Approximately three
times as many women as men have the
disease.ii Current treatment of RA includes the use
of non-steroidal anti-inflammatory drugs (NSAIDs), oral
conventional disease-modifying antirheumatic drugs (cDMARDs) – such
as methotrexate, the current standard of care, and injectable and
intravenous biological disease-modifying antirheumatic drugs
(bDMARDs) that target selected mediators implicated in the
pathogenesis of RA.iii Despite current treatment
options, many patients do not reach their therapeutic goals or are
not able to achieve sustained remission.iv There remains
an important need to provide additional treatment options to
improve overall patient care.
About Baricitinib Phase 3 Trials
Lilly and Incyte
conducted four successful pivotal Phase 3 clinical trials of
baricitinib in patients with moderate- to-severe active rheumatoid
arthritis to support regulatory submission in most countries. Two
of the four studies included pre-specified comparisons to approved
DMARDs: one to methotrexate (RA-BEGIN) and one to adalimumab
(RA-BEAM). An additional Phase 3 study was initiated to support
clinical development in China. The
clinical trial program includes a wide range of patients including
those who are methotrexate-naïve, inadequate responders to
methotrexate, inadequate responders to conventional synthetic
disease modifying antirheumatic drugs, or inadequate responders to
biologic DMARDs including TNF inhibitors. Patients completing any
of the Phase 3 studies can enroll in a long-term extension study.
For additional information on this clinical trial program, please
visit www.clinicaltrials.gov.
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 rheumatoid arthritis, and reflects Lilly's and
Incyte's current belief. 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 baricitinib will receive 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.
i WHO Global Burden of Disease Report, (table 7, page
32) 2004,
http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_full.pdf
(Accessed: May 16, 2017)
ii Arthritis Foundation, What is Rheumatoid
Arthritis?,
http://www.arthritis.org/about-arthritis/types/rheumatoid-arthritis/what-is-rheumatoid-arthritis.php
(Accessed: May 16, 2017)
iii Arthritis Foundation, Rheumatoid Arthritis
Treatment,
http://www.arthritis.org/about-arthritis/types/rheumatoid-arthritis/treatment.php
(Accessed: May 16, 2017)
iv McWilliams DF, Kiely PDW, Young A, Walsh DA.
Baseline factors predicting change from the initial DMARD treatment
during the first 2 years of rheumatoid arthritis: experience in the
ERAN inception cohort. BMC Musculoskeletal Disorders.
2013;14:1-7.
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)
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SOURCE Eli Lilly and Company