INDIANAPOLIS, Feb. 9, 2021 /PRNewswire/ --
The U.S. Food and Drug Administration (FDA) granted
Emergency Use Authorization (EUA) for investigational
bamlanivimab (LY-CoV555) 700 mg and etesevimab (LY-CoV016)
1400 mg together, Eli Lilly and Company (NYSE: LLY) announced
today. This therapy is authorized for the treatment of mild to
moderate COVID-19 in patients aged 12 and older who are at
high risk for progressing to severe COVID-19 and/or
hospitalization. Bamlanivimab and etesevimab should be administered
together via a single intravenous infusion as soon as possible
after a positive COVID-19 test and within 10 days of symptom
onset.
In addition, the FDA has authorized infusion times for
bamlanivimab alone and bamlanivimab and etesevimab together to be
as short as 16 or 21 minutes, respectively – a significant
reduction from the previously authorized time of 60 minutes. This
decision has been made in response to feedback received from
front-line nurses and doctors administering these infusions and are
aimed at reducing the burden on the healthcare system.
"Lilly has dedicated our time, resources, and expertise to
discover and develop therapies to treat COVID-19," said
Daniel Skovronsky, M.D., Ph.D.,
Lilly's chief scientific officer and president of Lilly Research
Laboratories. "Bamlanivimab alone under emergency use
authorization has already provided many people with an early
treatment option that could prevent hospitalizations and we are
excited to now add an additional therapeutic option with a similar
demonstrated clinical benefit. Additionally, with the risk of
resistance emerging as various strains of the virus arise,
bamlanivimab and etesevimab together could potentially allow
efficacy against a broader range of naturally occurring SARS-CoV-2
variants as these new strains spread around the world."
The EUA is based on Phase 3 data from the BLAZE-1 trial,
announced January 26, 2021, which
demonstrated bamlanivimab and etesevimab together reduced the risk
of COVID-19 hospitalizations and death by 70 percent. These data
replicate earlier results, published in The Journal of the
American Medical Association, in a much larger group of
patients. Additionally, the outcomes seen with bamlanivimab and
etesevimab together are consistent with the reduction in risk of
hospitalization or ER visits seen with bamlanivimab alone. The most
common adverse event more often reported for patients receiving
bamlanivimab and etesevimab together versus placebo was nausea on
the day of infusion.
While Phase 2 and Phase 3 trials evaluated a range of doses of
bamlanivimab alone and bamlanivimab and etesevimab together, data
demonstrated consistent and similar clinical effects among all
doses studied. Additionally, initial results from an ongoing Phase
2 study provide viral load and pharmacodynamic/pharmacokinetic data
which demonstrated bamlanivimab 700 mg and etesevimab 1400 mg
together produced similar effects to those observed in the Phase 3
trial with bamlanivimab 2800 mg and etesevimab 2800
mg together. Together, these data provide confidence in the
authorized dose, which expands available supply to help more
patients without sacrificing potential efficacy.
The FDA grants EUA 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
administration of bamlanivimab and etesevimab together is
authorized only for the duration of the declaration, unless the
authorization is terminated or revoked sooner. The authorization is
temporary and does not replace the formal review and approval
process. The administration of bamlanivimab and etesevimab together
remains investigational and has not been approved under a Biologics
License Application (BLA). Evaluation of its safety and efficacy is
ongoing in clinical trials. Data from these studies will be used to
support a future BLA submission for the treatment.
Bamlanivimab alone is authorized in numerous countries, while
bamlanivimab and etesevimab together is currently authorized in the
U.S. and Italy. Lilly will
continue working with global regulators to make these therapies
available around the world. In an effort to help as many patients
as possible, Lilly will continue to supply bamlanivimab alone under
the authorizations granted in various countries while continuing to
accelerate manufacturing of etesevimab for use around the world.
Lilly, in collaboration with Amgen, plans to manufacture up to 1
million doses of etesevimab for administration with bamlanivimab by
mid-2021. There are 100,000 doses ready immediately and an
additional 150,000 doses will be available throughout the first
quarter.
"As COVID-19 cases, hospitalizations and subsequent deaths
continue to rise, we are committed to working with the U.S.
government to supply our antibody therapies for use by patients
across the country," Skovronsky added.
Lilly anticipates procurement and allocation of bamlanivimab and
etesevimab together will mirror the process followed for
bamlanivimab alone – making the therapy available directly to
governments for allocation based on unmet needs. Global allocation
will be made based on Lilly's guiding
principles that aim to ensure access for patients with high
unmet need, no matter where they live.
For more information about the use of bamlanivimab alone or
bamlanivimab and etesevimab together for the treatment of mild to
moderate COVID-19 in high-risk patients under the FDA's emergency
use authorization, contact Lilly's 24-hour support line at
1-855-LillyC19 (1-855-545-5921). Patients and physicians can visit
covid.infusioncenter.org or the HHS Therapeutics Distribution
locator to find a potential treatment location.
For media resources, including product images and fact sheets,
please click here.
Important Information about bamlanivimab alone and
bamlanivimab and etesevimab together
Bamlanivimab and
etesevimab together and bamlanivimab alone have not been approved
by the FDA for any use. It is not known if bamlanivimab and
etesevimab together or bamlanivimab alone are safe and
effective for the treatment of COVID-19.
Bamlanivimab and etesevimab together and bamlanivimab alone
are authorized under Emergency Use Authorization only for the
duration of the declaration that circumstances exist justifying the
authorization of the emergency use under Section 564(b)(1) of the
Act, 21 U.S.C § 360bbb-3(b)(1), unless the authorization is
terminated or revoked sooner.
Healthcare providers should review the Fact Sheet for
information on the authorized use of bamlanivimab and etesevimab
together and bamlanivimab alone 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 bamlanivimab and etesevimab
together. Please see the FDA Letter of Authorization, Fact Sheet
for Healthcare Providers, and Fact Sheet for Patients, Parents and
Caregivers (English) (Spanish) for bamlanivimab alone.
Authorized Use and Important Safety
Information
Bamlanivimab and etesevimab together and
bamlanivimab alone are authorized for use under EUA for
treatment of mild to moderate COVID-19 in adults and pediatric
patients (12 years of age and older weighing at least 40
kg) with positive results of direct SARS-CoV-2 viral testing,
and who are at high risk for progressing to severe COVID-19 and/or
hospitalization.
Limitations of Authorized Use
- Bamlanivimab and etesevimab together and bamlanivimab alone are
not authorized for use in patients:
-
- who are hospitalized due to COVID-19, OR
- who require oxygen therapy due to COVID-19, OR
- who require an increase in baseline oxygen flow rate due to
COVID-19 in those on chronic oxygen therapy due to underlying
non-COVID-19 related comorbidity.
- Treatment with bamlanivimab and etesevimab together has not
been studied in patients hospitalized due to COVID-19. Benefit of
treatment with bamlanivimab alone has not been observed in patients
hospitalized due to COVID-19. Monoclonal antibodies, such as
bamlanivimab and etesevimab, may be associated with worse clinical
outcomes when administered to hospitalized patients with COVID-19
requiring high flow oxygen or mechanical ventilation.
Important Safety Information
There are limited
clinical data available for bamlanivimab and etesevimab
together and bamlanivimab alone. Serious and unexpected adverse
events may occur that have not been previously reported with
bamlanivimab and etesevimab together and bamlanivimab alone.
Hypersensitivity Including Anaphylaxis and
Infusion-Related Reactions
Serious hypersensitivity
reactions, including anaphylaxis, have been observed with
administration of bamlanivimab and etesevimab together and
bamlanivimab alone. If signs and symptoms of a clinically
significant hypersensitivity reaction or anaphylaxis occur,
immediately discontinue administration and initiate appropriate
medications and/or supportive care.
Infusion-related reactions have been observed with
administration of bamlanivimab and etesevimab together and
bamlanivimab alone. These reactions may be severe or life
threatening. Signs and symptoms of infusion-related reactions may
include:
- fever, difficulty breathing, reduced oxygen saturation, chills,
fatigue, arrhythmia (e.g. atrial fibrillation, sinus tachycardia,
bradycardia), chest pain or discomfort, weakness, altered mental
status, nausea, headache, bronchospasm, hypotension, hypertension,
angioedema, throat irritation, rash including urticaria, pruritus,
myalgia, dizziness, and diaphoresis.
If an infusion-related reaction occurs, consider slowing or
stopping the infusion and administer appropriate medications and/or
supportive care.
Clinical Worsening After Bamlanivimab
Administration
Clinical worsening of COVID-19 after
administration of bamlanivimab has been reported and may include
signs or symptoms of fever, hypoxia or increased respiratory
difficulty, arrhythmia (e.g., atrial fibrillation, sinus
tachycardia, bradycardia), fatigue, and altered mental status. Some
of these events required hospitalization. It is not known if these
events were related to bamlanivimab use or were due to progression
of COVID-19.
Limitations of Benefit and Potential Risk in Patients with
Severe COVID-19
Treatment with bamlanivimab and
etesevimab together has not been studied in patients hospitalized
due to COVID-19. Benefit of treatment with bamlanivimab alone has
not been observed in patient hospitalized due to COVID-19.
Monoclonal antibodies, such as bamlanivimab and etesevimab,
may be associated with worse clinical outcomes when administered to
hospitalized patients with COVID-19 requiring high flow oxygen or
mechanical ventilation. See Limitations of Authorized Use.
Adverse Events
Bamlanivimab and etesevimab
together
Based on Phase 2 data from BLAZE-1, nausea was the
most commonly reported adverse event, reported by 4% of subjects in
both bamlanivimab and etesevimab together and placebo groups.
Pruritus and pyrexia were more frequently reported from subjects
treated with both bamlanivimab and etesevimab (2% and 1%) compared
to placebo (1% and 0%, respectively).
Based on Phase 3 data from BLAZE-1, the most common adverse
events were nausea, dizziness, and rash. These events each occurred
in 1% of subjects treated with bamlanivimab and etesevimab together
and in 1% of placebo subjects.
Bamlanivimab alone
Adverse events reported in at least
1% of BLAZE-1 clinical trial participants on bamlanivimab 700 mg
alone or placebo were nausea (3% vs 4%), diarrhea (1% vs 5%),
dizziness (3% vs 2%), headache (3% vs 2%), pruritus (2% vs 1%) and
vomiting (1% vs 3%).
Use in Specific
Populations
Pregnancy
There are
insufficient data on the use of bamlanivimab and etesevimab
together and bamlanivimab alone during pregnancy. Bamlanivimab and
etesevimab together and bamlanivimab alone should only be used
during pregnancy if the potential benefit outweighs the potential
risk for the mother and the fetus.
Breastfeeding
There are no available data on
the presence of bamlanivimab or etesevimab in human or animal
milk, the effects on the breastfed infant, or the effects on milk
production. Breastfeeding individuals with COVID-19 should follow
practices according to clinical guidelines to avoid exposing the
infant to COVID-19.
About bamlanivimab
Bamlanivimab is a recombinant,
neutralizing human IgG1 monoclonal antibody (mAb) directed against
the spike protein of SARS-CoV-2. It is designed to block viral
attachment and entry into human cells, thus neutralizing the virus,
potentially treating COVID-19. Bamlanivimab emerged from the
collaboration between Lilly and AbCellera to create antibody
therapies for the prevention and treatment of COVID-19. Lilly
scientists rapidly developed the antibody in less than three months
after it was discovered by AbCellera and the scientists at the
National Institute of Allergy and Infectious Diseases (NIAID)
Vaccine Research Center. It was identified from a blood sample
taken from one of the first U.S. patients who recovered from
COVID-19.
Lilly has successfully completed a Phase 1 study of
bamlanivimab in hospitalized patients with COVID-19
(NCT04411628). A Phase 2/3 study in people recently diagnosed
with COVID-19 in the ambulatory setting (BLAZE-1, NCT04427501) is
ongoing. A Phase 3 study of bamlanivimab for the prevention of
COVID-19 in residents and staff at long-term care facilities
(BLAZE-2, NCT04497987) is also ongoing. In addition, bamlanivimab
is being tested in the National Institutes of Health-led ACTIV-2
study in ambulatory COVID-19 patients.
About etesevimab
Etesevimab (LY-CoV016, also known as
JS016) is a recombinant fully human monoclonal neutralizing
antibody, which specifically binds to the SARS-CoV-2 surface spike
protein receptor binding domain with high affinity and can block
the binding of the virus to the ACE2 host cell surface receptor.
Point mutations were introduced into the native human IgG1 antibody
to mitigate effector function. Lilly licensed etesevimab from
Junshi Biosciences after it was jointly developed by Junshi
Biosciences and Institute of Microbiology, Chinese Academy of
Science (IMCAS). Junshi Biosciences leads development
in Greater China, while Lilly leads development in the rest of
the world.
Lilly has successfully completed a Phase 1 study (NCT04441931)
of etesevimab in healthy U.S. volunteers to evaluate the safety,
tolerability, pharmacokinetics and immunogenicity. A Phase 2/3
study in people recently diagnosed with COVID-19 in the ambulatory
setting (BLAZE-1, NCT04427501) is ongoing. Junshi Biosciences has
completed a similar Phase 1 study in healthy volunteers in
China and has initiated Phase
1b/2 trials in COVID-19 patients
globally.
About BLAZE-1
BLAZE-1 (NCT04427501) is
a randomized, double-blind, placebo-controlled Phase 2/3 study
designed to assess the efficacy and safety of bamlanivimab alone or
bamlanivimab and etesevimab together for the treatment of
symptomatic COVID-19 in the outpatient setting. To be eligible,
patients were required to have mild or moderate symptoms of
COVID-19 as well as a positive SARS-CoV-2 test based on a sample
collected no more than three days prior to drug infusion.
In the Phase 2 portion of BLAZE-1, cohorts of mild to moderate
recently diagnosed COVID-19 patients, were randomized to one of
three doses of bamlanivimab (700 mg, 2800 mg, and 7000
mg), bamlanivimab 2800 mg plus etesevimab 2800 mg, or placebo.
Results from the Phase 2 cohorts of BLAZE-1 were published in the
New England Journal of Medicine and The Journal of the
American Medical Association.
In the Phase 3 portion of BLAZE-1, the combination therapy arms
enrolled mild to moderate, recently diagnosed COVID-19 patients who
are at high risk for progressing to severe COVID-19 and/or
hospitalization, studying bamlanivimab 2800 mg plus etesevimab 2800
mg versus placebo. The primary outcome measure for the Phase 3
portion of the BLAZE-1 trial was the percentage of participants who
experience COVID-related hospitalizations or death from any cause
by day 29. The key secondary endpoints were change from baseline to
day 7 in SARS-CoV-2 viral load, persistently high SARS-CoV-2 viral
load on day 7, time to sustained symptom resolution, and
COVID-related hospitalization, ER visit or death from any cause
from baseline by day 29. Additional endpoints include change from
baseline in viral load at other time points, symptom improvement,
symptom resolution, as well as safety.
The study is ongoing with additional treatment arms. Across all
treatment arms, the trial will enroll up to 3,300 participants.
About BLAZE-4
BLAZE-4 (NCT04634409) is a
randomized, double-blind, placebo-controlled trial designed to
assess the efficacy and safety of bamlanivimab alone, and
bamlanivimab and etesevimab together, at various doses, versus
placebo for the treatment of symptomatic COVID-19 in the outpatient
setting. Across all treatment arms, the trial will enroll an
estimated 1,000 participants in the
United States and Puerto
Rico.
The primary outcome measure is percentage of participants who
have a viral load greater than 5.27 at day 7. Additional endpoints
include change from baseline to day 7 in SARS-CoV-2 viral load,
percentage of participants who experience COVID-related
hospitalization, ER visit or death from baseline through day 29, as
well as safety.
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.
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 www.lilly.com/news. P-LLY
Lilly 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 bamlanivimab (LY-CoV555) alone or bamlanivimab
and etesevimab (LY-CoV016) together as potential treatments for
patients with COVID-19, as well as its supply, and reflects Lilly's
current beliefs and expectations. However, as with any such
undertaking, there are substantial risks and uncertainties in the
process of drug development and commercialization. Among other
things, there can be no guarantee that future study results
will be consistent with the results to date, that bamlanivimab
alone or bamlanivimab and etesevimab together will prove to be safe
and effective treatments or successful preventative therapies for
COVID-19, that bamlanivimab alone or bamlanivimab and etesevimab
together will receive regulatory approvals or additional
authorizations, or that Lilly can provide an adequate supply of
bamlanivimab alone or bamlanivimab and etesevimab together in all
circumstances. For a further discussion of these and other
risks and uncertainties that could cause actual results to differ
from Lilly's expectations, please see Lilly's most recent Forms
10-K and 10-Q filed with the U.S. Securities and Exchange
Commission. Lilly undertakes no duty to update forward-looking
statements.
PP-LI-US-0373 02/2021 ©Lilly USA, LLC 2021. All rights reserved.
#
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Refer to:
|
Molly McCully;
mccully_molly@lilly.com; 317-478-5423 (Media)
|
|
Dani Barnhizer;
dbarnhizer@lilly.com; 317-607-6119 (Media)
|
|
Kevin Hern;
hern_kevin_r@lilly.com; 317-277-1838 (Investors)
|
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