INDIANAPOLIS, April 8, 2021 /PRNewswire/ -- Eli Lilly and
Company (NYSE: LLY) and Incyte (NASDAQ:INCY) announced today
results of COV-BARRIER, a Phase 3 study evaluating baricitinib 4 mg
once daily plus standard of care (SoC) versus placebo plus SoC. The
trial did not meet statistical significance on the primary
endpoint, which was defined as a difference in the proportion of
participants progressing to the first occurrence of non-invasive
ventilation including high flow oxygen or invasive mechanical
ventilation including extracorporeal membrane oxygenation (ECMO) or
death by Day 28. Baricitinib-treated patients were 2.7 percent less
likely than those receiving standard of care to progress to
ventilation (non-invasive or mechanical) or death, a difference
that was not statistically significant (odds ratio [OR]: 0.85; 95%
CI 0.67, 1.08; p=0.1800).
In COV-BARRIER, treatment with baricitinib in addition to SoC
(which included 79% receiving corticosteroids and 19% receiving
remdesivir, with some receiving both) resulted in a significant
reduction (nominal p-value=0.0018) in death from any cause by 38
percent (n/N: 62/764 [8.1%] baricitinib, 100/761 [13.1%] placebo;
hazard ratio [HR]: 0.57; 95% CI: 0.41, 0.78) by Day 28. A numerical
reduction in mortality was observed for all baseline severity
subgroups of baricitinib-treated patients and was most pronounced
for patients receiving non-invasive mechanical ventilation at
baseline (17.5% versus 29.4% for baricitinib plus SoC versus SoC;
hazard ratio [HR]: 0.52; 95% CI: 0.33, 0.80; nominal
p-value=0.0065). A reduction in mortality was also seen for the
pre-specified subgroups of patients being treated with or without
corticosteroids at baseline.
"There remains a driving unmet need for treatments with the
potential to further decrease mortality for COVID-19 patients,"
said co-primary investigator E. Wesley
Ely, M.D., MPH, professor of medicine and co-director of the
Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center
at Vanderbilt University Medical
Center. "While COV-BARRIER did not hit the primary endpoint based
on stages of disease progression, the data show that baricitinib
meaningfully reduced the risk of mortality above and beyond the
recommended standard of care, without additional safety risks.
These important findings advance our pursuit of treatment options
to save lives in hospitalized COVID-19 patients."
The frequency of adverse events and serious adverse events were
generally similar in the baricitinib (44.5% and 14.7%,
respectively) and placebo (44.4% and 18.0%, respectively) groups.
Serious infections and venous thromboembolism (VTE) occurred in 8.5
percent and 2.7 percent of patients treated with baricitinib,
respectively, versus 9.8 percent and 2.5 percent of patients
treated with placebo. No new safety signals potentially related to
the use of baricitinib were identified.
Lilly intends to publish detailed results of this study in a
peer-reviewed journal in the coming months. Lilly will share the
data from COV-BARRIER with regulatory authorities in the U.S.,
European Union and other geographies to evaluate next steps for
baricitinib for the treatment of hospitalized COVID-19
patients.
"Since the beginning of the pandemic, we have worked to expand
the science behind COVID-19 therapies," said Ilya Yuffa, senior vice president and president
of Lilly Bio-Medicines. "Even though the study did not show a
statistically-significant benefit on the primary endpoint, this
trial showed the largest effect reported to date for reduction in
mortality observed for this patient population with COVID-19. As
there remains an urgent need to reduce COVID-related deaths in
hospitalized patients, we hope these results will provide further
understanding and support for baricitinib's potential role in
treatment on top of the current standard of care."
COV-BARRIER (NCT04421027) is the first global, randomized,
double-blind, placebo-controlled study to assess baricitinib versus
placebo in patients hospitalized with COVID-19 receiving SoC which
could include corticosteroids, antimalarials, antivirals, and/or
azithromycin. This Phase 3 study of 1,525 patients began in
June 2020 and enrolled hospitalized
patients who did not require supplemental oxygen (ordinal scale
[OS] 4), required supplemental oxygen (OS 5) or high-flow
oxygen/non-invasive ventilation (OS 6). Patients were also required
to have at least one increased marker of inflammation, an indicator
of risk of disease progression. All patients were treated with SoC
per local clinical practice including 79 percent receiving
corticosteroids (with 91% of those patients receiving
dexamethasone) and 19 percent receiving remdesivir at baseline,
with some receiving both. Patients were randomized 1:1 to
baricitinib 4 mg or placebo for up to 14 days or until discharge
from the hospital. The study was global and included diverse
patients from several countries with high prevalence of COVID-19
hospitalizations – the U.S., Brazil, Mexico, Argentina, Russia, India, UK, Spain, Italy,
Germany, Japan and Korea. An addendum to the study was
initiated in December 2020 to include
mechanically ventilated (OS 7) patients at baseline and is
currently enrolling.
The COV-BARRIER trial was designed to complement the Adaptive
COVID-19 Treatment Trial (ACTT-2) sponsored by the National
Institute of Allergy and Infectious Diseases (NIAID), part of the
National Institutes of Health (NIH). ACTT-2 began in
May 2020 and has published results
from 1,033 patients. Patients who received baricitinib in
combination with remdesivir had a shorter median time to recovery
compared to patients who received remdesivir alone. In ACTT-2,
there was a significant reduction in the proportion of patients
progressing to noninvasive ventilation, invasive mechanical
ventilation or death, in the baricitinib plus remdesivir group
compared to remdesivir. A numerical decrease in mortality risk
through Day 29 was observed in patients treated with baricitinib
plus remdesivir compared to remdesivir.
"While the trend observed for the primary endpoint was not
significant, the demonstration of a potential effect on mortality
is a clinically important finding. This effect on mortality was
seen with or without corticosteroids and/or remdesivir at the time
of enrollment," said Vincent C.
Marconi, M.D., professor of medicine and global health at
Emory University School of Medicine and
Emory's Rollins
School of Public Health, a co-principal investigator of
COV-BARRIER and a co-investigator on the ACTT-2 study. "These
results – along with those from the NIAID-sponsored ACTT-2 study
evaluating baricitinib in combination with remdesivir – add to the
growing body of data supporting the use of baricitinib in certain
hospitalized patients with COVID-19."
Additional research is ongoing to further evaluate the potential
role of baricitinib in COVID-19, including NIAID's ACTT-4 trial
(evaluating the efficacy and safety of baricitinib or dexamethasone
in combination with remdesivir in hospitalized adults with COVID-19
on supplemental oxygen), the RECOVERY trial in the UK and several
investigator-initiated trials.
An emergency use authorization (EUA) was issued by the U.S. Food
and Drug Administration (FDA) on Nov. 19,
2020 for baricitinib in combination with remdesivir in
hospitalized patients with COVID-19 requiring supplemental oxygen,
invasive mechanical ventilation, or ECMO. Please see below for
important warnings and information about the authorized use of
baricitinib in the U.S. More than 200,000 patients globally
are estimated to have been treated with baricitinib for
COVID-19.
Baricitinib, an oral JAK inhibitor, was discovered
by Incyte and licensed to Lilly. It 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 active
rheumatoid arthritis (RA) and in the European Union and
Japan for the treatment of adult
patients with moderate to severe atopic dermatitis (AD) who are
candidates for systemic therapy.
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) in combination with remdesivir, for treatment
of suspected or laboratory confirmed coronavirus disease 2019
(COVID-19) in hospitalized adults and pediatric patients 2 years of
age or older, requiring supplemental oxygen, invasive mechanical
ventilation, or extracorporeal membrane oxygenation
(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 authorization is
terminated or revoked sooner.
For information on the authorized use of baricitinib and
mandatory requirements under the EUA, please review 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: 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: Evaluate 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.
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 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.
There are limited clinical data available for baricitinib use in
coronavirus 2019 (COVID-19). Additional information regarding
baricitinib for its FDA-approved indication, including safety
information, may be found in the full Prescribing Information,
including Boxed Warning about Serious Infections, Malignancies, and
Thrombosis, and Medication Guide.
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.
BC HCP EUA ISI 19NOV2020
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 being studied to understand
their potential in treating complications of COVID-19, and the
company is collaborating with partner companies to discover and
develop 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 and here for baricitinib's EUA.
About OLUMIANT ® (baricitinib)
OLUMIANT is a once-daily, oral JAK inhibitor approved in
the U.S. and more than 70 countries as a treatment for
adults with moderate to severe rheumatoid arthritis and was
recently approved in the European Union and Japan for the treatment of adult patients with
moderate to severe atopic dermatitis who are candidates for
systemic therapy. The U.S. FDA-approved labeling for
Olumiant includes a Boxed Warning for Serious Infections,
Malignancy, and Thrombosis. See the full Prescribing
Information here. Baricitinib is also being investigated in
alopecia areata (AA), juvenile idiopathic arthritis (JIA) and
systematic lupus erythematosus (SLE).
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.
Cautionary Statement Regarding Forward-Looking
Statements
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
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 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, that OLUMIANT will receive additional regulatory
approvals or authorizations or be commercially successful, or that
OLUMIANT will be safe and effective as a treatment for COVID-19.
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:
|
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)
|
|
Christine Chiou;
cchiou@incyte.com; +1-302-274-4773 (Incyte investors)
|
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