INDIANAPOLIS, Nov. 19, 2020 /PRNewswire/ -- Eli Lilly and
Company (NYSE: LLY) and Incyte (NASDAQ: INCY) announced today
that the U.S. Food and Drug Administration (FDA) issued an
Emergency Use Authorization (EUA) for the distribution and
emergency use of baricitinib to be used in combination with
remdesivir in hospitalized adult and pediatric patients two years
of age or older with suspected or laboratory confirmed COVID-19 who
require supplemental oxygen, invasive mechanical ventilation, or
extracorporeal membrane oxygenation (ECMO).
"Since the start of the COVID-19 pandemic, Lilly has been
committed to finding potential treatments to help people around the
world who've been impacted by this virus," said David A. Ricks, Lilly chairman and CEO. "Today's
FDA action for baricitinib marks the second Lilly therapy to be
granted an EUA, in addition to the recent neutralizing antibody EUA
for high-risk non-hospitalized patients, increasing the number of
treatment options for COVID-19 patients at different stages of the
disease. This is an important milestone for hospitalized patients
on oxygen, as baricitinib may help speed their recovery."
The FDA grants emergency use authorization to provide
availability of a medicine that may help diagnose, treat or prevent
a life-threatening disease when no adequate and approved
alternatives are available. This use of baricitinib is authorized
only for the duration of the declaration that circumstances exist
justifying the authorization of the emergency use, unless the
authorization is terminated or revoked sooner. The authorization is
temporary and does not replace the formal review and approval
process. In the U.S., baricitinib has not been approved by the FDA
to treat COVID-19, and the efficacy, safety and optimal duration of
treatment of baricitinib for COVID-19 has not been established.
This is the first combination regimen authorized by FDA. Evaluation
of baricitinib's efficacy and safety as a treatment for COVID-19 is
ongoing in clinical trials.
Scientific evidence supporting this EUA:
The EUA is
based on data from the Adaptive COVID-19 Treatment Trial (ACTT-2),
a randomized double-blind, placebo-controlled study to evaluate the
efficacy and safety of baricitinib in combination with remdesivir
versus placebo with remdesivir in hospitalized patients with or
without oxygen requirements conducted by the National Institute of
Allergy and Infectious Diseases (NIAID), part of the National
Institutes of Health (NIH). All patients received standard
supportive care by the trial site hospital. The recommended dose
for this EUA is baricitinib 4-mg once daily for 14 days or until
hospital discharge.
Summary of Key Efficacy and Safety Findings
- Patients treated with baricitinib in combination with
remdesivir had a significant reduction in median time to recovery
from 8 to 7 days (12.5% improvement) compared to remdesivir [hazard
ratio: 1.15; 95% CI 1.00, 1.31; p=0.047].
- Patients treated with baricitinib in combination with
remdesivir were more likely to have a better clinical status at Day
15 compared to patients treated with remdesivir [odds ratio: 1.26;
95% CI 1.01, 1.57; p=0.044].
- The proportion of patients who progressed to ventilation
(non-invasive or invasive) or died by Day 29 was lower in
baricitinib in combination with remdesivir (23%) compared to
remdesivir (28%) [odds ratio: 0.74; 95% CI 0.56, 0.99;
p=0.039].
- The proportion of patients who died by Day 29 was 4.7% for
baricitinib in combination with remdesivir vs. 7.1% for remdesivir,
a relative reduction of 35% [Kaplan
Meier estimated difference in Day 29 probability of
mortality: -2.6% (95% CI -5.8%, 0.5%)].
- Adverse events and serious adverse events were reported in 41%
and 15% of patients treated with baricitinib in combination with
remdesivir, respectively, vs. 48% and 20% in patients treated with
remdesivir. Infections and venous thromboembolism (VTE) occurred in
6% and 4% of patients treated with baricitinib in combination with
remdesivir, respectively, vs. 10% and 3% of patients treated with
remdesivir. No new safety signals were identified for
baricitinib-treated patients.
"The results of ACTT-2 provide physicians and the medical
community much-needed insights and randomized placebo-controlled
evidence supporting the use of baricitinib in combination with
remdesivir for the treatment of hospitalized patients with
COVID-19; also importantly, the progression to ventilation or death
was significantly reduced with the baricitinib-remdesivir
combination," said Andre Kalil,
M.D., professor at the University of Nebraska
Medical Center and a principal investigator of the ACTT
studies. "Few treatment options have received an EUA to treat
COVID-19 so the authorization of baricitinib is an important step
that will give healthcare providers another clinical tool to help
patients with advanced disease."
NIAID and the study investigators expect to have the full
analysis published in a peer-reviewed manuscript soon.
Baricitinib, an oral JAK inhibitor discovered by Incyte and
licensed to Lilly, is approved and commercially available as
OLUMIANT in the U.S. and more than 70 countries as a treatment for
adults with moderate to severe rheumatoid arthritis (RA) and was
recently approved in the European Union for the treatment of adult
patients with moderate to severe atopic dermatitis who are
candidates for systemic therapy.
"As a company, we have worked quickly and collaboratively to
determine the potential utility of our medicines as treatments for
COVID-19 and its related complications," said Hervé Hoppenot,
Incyte CEO. "We are pleased that the FDA has authorized the
use of baricitinib in combination with remdesivir for COVID-19, and
look forward to the opportunity to make more therapies available to
patients around the world affected by the global
pandemic."
Access to baricitinib
Under the EUA, inpatient
pharmacies in the U.S. may order OLUMIANT (baricitinib) 1-mg and
2-mg tablets through Lilly authorized specialty distributors. A
current list of Lilly's authorized distributors of record for the
EUA is available at lillytrade.com. More details about these
efforts are available here or by contacting Lilly's 24-hour
support line at 1-855-LillyC19 (1-855-545-5921).
Lilly is working with hospitals, healthcare professionals and
governments to facilitate patient access to baricitinib and
continues to explore the medicine's potential use in COVID-19 with
other regulatory agencies outside the U.S. With respect to supply,
Lilly remains confident in being able to meet the needs of patients
under the EUA in the U.S., as well as for existing approved
indications around the world.
Important information about baricitinib for
COVID-19
This EUA permits the emergency use of baricitinib,
in combination with remdesivir, for treatment of suspected or
laboratory confirmed COVID-19 in hospitalized adults and pediatric
patients two years of age or older requiring supplemental oxygen,
invasive mechanical ventilation, or ECMO. Although there is limited
safety data, no new safety issues have been identified. Physicians
should avoid the use of baricitinib in patients with known active
tuberculosis and consider if the potential benefits outweigh the
potential risks in patients with active serious infections other
than COVID-19 or chronic/recurrent infections. Prophylaxis for VTE
is recommended unless contraindicated. If clinical features of deep
vein thrombosis/pulmonary embolism occur, patients should be
evaluated promptly and treated appropriately. Evaluate renal,
hematologic and hepatic laboratory values at baseline and
thereafter, and monitor closely when treating patients with
abnormal baseline and post-baseline laboratory values. Avoid use of
live vaccines with baricitinib. If a serious hypersensitivity
occurs, discontinue baricitinib while evaluating the potential
causes of the reaction. Serious venous thrombosis, including
pulmonary embolism, and serious infections have been observed in
COVID-19 patients treated with baricitinib.
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). For media resources, including product images
and fact sheets, please click here.
There are other ongoing trials with baricitinib in COVID-19
hospitalized patients. In June 2020,
Lilly initiated a Phase 3 randomized, double-blind,
placebo-controlled study to evaluate the efficacy and safety of
baricitinib versus background therapy in hospitalized adults with
COVID-19. The study includes a diverse patient population from
Latin America, the U.S.,
Europe and Asia. Further information about this Phase 3
trial and other investigator-initiated trials can be accessed
here or www.lillytrialguide.com.
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: 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, 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 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 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.
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 Lilly's COVID-19 Efforts
Lilly is bringing the
full force of its scientific and medical expertise to attack the
coronavirus pandemic around the world. Existing Lilly medicines are
now being studied to understand their potential in treating
complications of COVID-19, and the company is collaborating with
two partner companies to discover novel antibody treatments for
COVID-19. Lilly is testing both single antibody therapy as well as
combinations of antibodies as potential therapeutics for COVID-19.
Click here for resources related to Lilly's COVID-19
efforts.
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 Olumiant is also
approved in the European Union for the treatment of adult patients
with moderate to severe atopic dermatitis who are candidates for
systemic therapy. 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
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.
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.
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 contains forward-looking statements (as that
term is defined in the Private Securities Litigation Reform Act of
1995) about OLUMIANT (baricitinib) as a potential treatment for
patients with COVID-19 and as a treatment for patients with
rheumatoid arthritis, and about the supply of OLUMIANT, and
reflects Lilly's and Incyte's current beliefs. This press release
also contains forward-looking statements about Lilly's neutralizing
antibodies as potential treatments for patients with or at risk of
infection from COVID-19 and reflects Lilly 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 or Lilly's neutralizing antibody treatments will
prove to be safe and effective treatments for patients with
COVID-19, that OLUMIANT or Lilly's neutralizing antibody treatments
will receive additional regulatory approvals or authorizations,
that OLUMIANT will continue to be commercially successful, or that
we can provide an adequate supply of OLUMIANT or Lilly's
neutralizing antibody treatments in all circumstances. 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.
PP-BC-US-0007 11/2020 ©Lilly USA, LLC 2020. All rights reserved.
1 Olumiant Prescribing Information, 2020.
2 Walker JG and Smith MD. J Rheumatol.
2005;32;1650-1653.
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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