INDIANAPOLIS, Oct. 7, 2020 /PRNewswire/ -- Eli Lilly and
Company (NYSE: LLY) today announced additional details on its
SARS-CoV-2 neutralizing antibody programs – including interim data
on combination therapy in recently diagnosed patients with
mild-to-moderate COVID-19 – and plans to make these therapies
broadly available to patients.
"Our teams have worked tirelessly the last seven months to
discover and develop these potential antibody treatments," said
Daniel Skovronsky, M.D., Ph.D.,
Lilly's chief scientific officer and president of Lilly Research
Laboratories. "We believe the data generated to date provide
sufficient evidence that both monotherapy and combination therapy
may be effective to treat COVID-19 in patients with a high risk for
serious outcomes. Lilly is diligently working with regulators
around the world to make these treatments available."
Investors, media and the general public are invited to a
conference call today at noon EDT,
where Lilly will provide more data and discussion on these
programs. The webcast information is available here. A replay
will also be available on the website following the conference
call.
Combination therapy clinical trial data
Data from a new interim analysis of the BLAZE-1 clinical trial
showed that combination therapy with two of Lilly's SARS-CoV-2
neutralizing antibodies reduced viral load, symptoms and
COVID-related hospitalization and ER visits. The randomized,
double-blind, placebo-controlled Phase 2 study evaluated LY-CoV555
and LY-CoV016, which bind complementary regions of the SARS-CoV-2
spike protein, for the treatment of symptomatic COVID-19 in the
outpatient setting. The combination cohort enrolled recently
diagnosed patients with mild-to-moderate COVID-19, who were
assigned to 2800 mg of each antibody (n=112) or placebo
(n=156).
The combination therapy significantly reduced viral load at day
11 (p=0.011), meeting the primary endpoint of the study. Most
patients, including those receiving placebo, demonstrated near
complete viral clearance by day 11. Further, combination treatment
reduced viral levels at day 3 (p=0.016) and day 7
(p<0.001)—earlier time points during the course of infection
when higher viral loads are typically seen. Combination therapy
also significantly reduced the time-weighted average change from
baseline from day 1 to 11. An exploratory analysis showed that the
proportion of patients with persistent high viral load at day 7 for
combination therapy was lower (3.0 percent) versus placebo (20.8
percent), corresponding to a nominal p value of p<0.0001 without
multiplicity adjustment. No emergent putative resistance variants
have been observed thus far in patients treated with combination
therapy.
Combination therapy also met prespecified clinical endpoints,
including the time-weighted average change from baseline in total
symptom score from day 1 to 11 (p=0.009). The improvement in
symptoms was observed as early as three days after dosing and was
similar in magnitude and timing to improvements previously seen
with LY-CoV555 monotherapy. The rate of COVID-related
hospitalization and ER visits was lower for patients treated with
combination therapy (0.9 percent) versus placebo (5.8 percent), a
relative risk reduction of 84.5 percent (p=0.049). This was also
similar to observations for LY-CoV555 monotherapy.
Combination therapy has been generally well tolerated with no
drug-related serious adverse events. In LY-CoV555 monotherapy
studies there have been isolated drug-related infusion reactions or
hypersensitivity that were generally mild (two reported as serious infusion reactions,
all patients recovered). Treatment emergent adverse events were
comparable to placebo for both LY-CoV555 monotherapy and
combination therapy.
Lilly is working to publish the monotherapy and combination
therapy data in peer-reviewed journals as soon as possible.
Manufacturing and supply update
To be able to quickly provide treatment to patients around the
world, Lilly invested in large-scale manufacturing of both
antibodies at risk – even before data demonstrated their potential
to become a meaningful therapeutic option for COVID-19.
For monotherapy, Lilly is focused on the 700 mg dose of
LY-CoV555 since similar clinical effects were seen across all dose
levels tested in BLAZE-1. Lilly anticipates it could supply as many
as one million doses of 700 mg LY-CoV555 monotherapy in Q4 2020,
with 100,000 available in October. With respect to the supply of
combination therapy, Lilly anticipates it will have 50,000 doses
available in Q4 2020. The supply of combination therapy will
increase substantially beginning in Q1 2021, as additional
manufacturing resources come online throughout the year, including
Lilly's recently announced manufacturing collaboration with Amgen
(NASDAQ: AMGN). Lilly is also pursuing additional partnerships to
provide antibodies to resource-limited countries.
Regulatory update
Based on the combination therapy data, along with the previously
disclosed findings for LY-CoV555 monotherapy, Lilly has engaged
global regulators, including the FDA regarding potential EUA. Lilly
has now submitted an initial request for EUA for LY-CoV555
monotherapy in higher-risk patients who have been recently
diagnosed with mild-to-moderate COVID-19. We expect to submit a
subsequent request for EUA for combination therapy in November,
pending clinical trial enrollment, once additional safety data
accumulate and sufficient supply is manufactured. Lilly anticipates
having data to support a biologics license application (BLA)
submission for combination therapy as early as Q2 2021.
Conversations with global regulators are ongoing.
The BLAZE-1 clinical trial (NCT04427501) continues to enroll a
confirmatory cohort of higher-risk patients who have been recently
diagnosed with mild-to-moderate COVID-19, testing the ability of
the antibody combination to reduce the number of patients with
persistent high viral load and reduce COVID-related
hospitalizations. In addition, Lilly is studying lower doses of
combination therapy and alternative delivery options in planned or
ongoing clinical trials. Other ongoing clinical trials include a
Phase 3 study of LY-CoV555 monotherapy for the prevention of
COVID-19 in residents and staff at long-term care facilities
(BLAZE-2, NCT04497987). In addition, LY-CoV555 monotherapy is being
tested in the National Institutes of Health-led ACTIV-2 and ACTIV-3
studies of ambulatory and hospitalized COVID-19 patients. Data from
these other ongoing trials are not yet available. Thus far, over
850 trial participants have been dosed with LY-CoV555 (alone or in
combination with LY-CoV016), contributing to the safety data
supporting this potential treatment.
Open-label pragmatic study in COVID-19 outpatients
To generate additional efficacy and safety data, Lilly plans to
initiate a pragmatic, open-label study in the coming weeks,
enrolling patients treated with either monotherapy or combination
therapy, with a focus on collecting data regarding
hospitalizations, deaths and safety.
Moving forward, LY-CoV555 and LY-CoV016 will be referred to as
bamlanivimab and etesevimab, respectively.
About BLAZE-1
BLAZE-1 (NCT04427501) is a randomized, double-blind,
placebo-controlled Phase 2 study designed to assess the efficacy
and safety of LY-CoV555 and LY-CoV016 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.
The monotherapy arms of the trial enrolled mild-to-moderate
recently diagnosed COVID-19 patients, studying three doses of
LY-CoV555 (700 mg, 2800 mg, and 7000 mg) versus placebo. The
combination arm of the trial enrolled mild-to-moderate, recently
diagnosed COVID-19 patients, studying LY-CoV555 2800 mg plus
LY-CoV016 2800 mg versus placebo. Placebo patients were shared
across all therapy arms in the completed cohorts.
The primary outcome measure for these completed arms of the
BLAZE-1 trial was change from baseline to day 11 in SARS-CoV-2
viral load. Additional endpoints include the percentage of
participants who experience COVID-related hospitalization, ER visit
or death from baseline through day 29, as well as safety.
The study is ongoing with additional treatment arms. Across all
treatment arms, the trial will enroll an estimated 800
participants.
About bamlanivimab (LY-CoV555)
LY-CoV555 is a potent, neutralizing 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 preventing and treating
COVID-19. LY-CoV555 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 enrollment and primary safety
assessments of LY-CoV555 in a Phase 1 study of hospitalized
patients with COVID-19 (NCT04411628) and long-term follow-up is
ongoing. A Phase 2 study in people recently diagnosed with
COVID-19 in the ambulatory setting (BLAZE-1, NCT04427501) is
ongoing. Lilly recently initiated a Phase 3 study for the
prevention of COVID-19 in residents and staff at long-term care
facilities (BLAZE-2, NCT04497987). In addition, LY-CoV555 is being
tested in the National Institutes of Health-led ACTIV-2 and ACTIV-3
studies of ambulatory and hospitalized COVID-19 patients.
About etesevimab (LY-CoV016)
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 effectively 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.
A SARS-CoV-2 challenge study was conducted in rhesus macaques and
showed LY-CoV016 is effective for both prophylactic and therapeutic
venues against SARS-CoV-2 infection. Lilly licensed LY-CoV016 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 LY-CoV016 in healthy U.S. volunteers to evaluate the safety,
tolerability, pharmacokinetics and immunogenicity. LY-CoV016 has
been well tolerated and no drug-related severe adverse events
(SAEs) have been observed to date.
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 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 media 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 LY-CoV555 and LY-CoV016 as
a potential treatment for patients with or at risk of
infection from COVID-19 and reflects Lilly's current
beliefs. 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 LY-CoV555 and
LY-CoV016 will prove to be a safe and effective treatment or
preventative for COVID-19, that LY-CoV555 and LY-CoV016 will
receive regulatory approvals or authorizations, or that we can
provide an adequate supply of LY-CoV555 and LY-CoV016 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.
Refer to:
|
Molly McCully;
mccully_molly@lilly.com; 317-478-5423 (Media)
|
|
Kevin Hern;
hern_kevin_r@lilly.com; 317-277-1838
(Investors)
|
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SOURCE Eli Lilly and Company