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FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
to Rule 13a-16 or 15d-16 of
the
Securities Exchange Act of 1934
For the
month of August 2021
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
AZD7442 prophylaxis
trial met primary endpoint
20
August 2021 07:00 BST
AZD7442 PROVENT Phase III prophylaxis trial met primary
endpoint
in preventing COVID-19
77% reduced risk of developing symptomatic COVID-19
First long-acting antibody combination to prevent
COVID-19
Positive high-level results from the PROVENT Phase III pre-exposure
prophylaxis trial showed AstraZeneca's AZD7442 achieved a
statistically significant reduction in the incidence of symptomatic
COVID-19, the trial's primary endpoint.
AZD7442, a combination of two long-acting antibodies (LAAB),
reduced the risk of developing symptomatic COVID-19 by 77% (95%
confidence interval (CI): 46, 90), compared to placebo. The trial
accrued 25 cases of symptomatic COVID-19 at the primary
analysis.
There were no cases of severe COVID-19 or COVID-19-related deaths
in those treated with AZD7442. In the placebo arm, there were three
cases of severe COVID-19, which included two deaths.
AZD7442 is the first antibody combination (non-vaccine) modified to
potentially provide long-lasting protection that has demonstrated
prevention of COVID-19 in a clinical trial.
The trial included 5,197 participants in a 2:1
randomisation AZD7442 to placebo. The primary analysis was based on
5,172 participants who did not have SARS-CoV-2 infection at
baseline.
More than 75% of participants had co-morbidities, which include
conditions that have been reported to cause a reduced immune
response to vaccination.
The LAAB was well tolerated and preliminary analyses show adverse
events were balanced between the placebo and AZD7442
groups.
Myron J. Levin, MD, Professor of Pediatrics and Medicine,
University of Colorado School of Medicine, US, and principal
investigator on the trial, said: "The PROVENT data show that one
dose of AZD7442, delivered in a convenient intramuscular form, can
quickly and effectively prevent symptomatic COVID-19. With these
exciting results, AZD7442 could be an important tool in our arsenal
to help people who may need more than a vaccine to return to their
normal lives."
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, said: "We need additional approaches for individuals who
are not adequately protected by COVID-19 vaccines. We are very
encouraged by these efficacy and safety data in high-risk people,
showing our long-acting antibody combination has the potential to
protect from symptomatic and severe disease, alongside vaccines. We
look forward to sharing further data from the AZD7442 Phase III
clinical trial programme later this year."
AZD7442 was optimised using AstraZeneca's proprietary YTE half-life
extension technology, which could afford up to 12 months of
protection from COVID-19, and is delivered by intramuscular
injection.
Preliminary 'in vitro' findings from investigators at Oxford
University and Columbia University demonstrate that AZD7442
neutralises recent emergent SARS-CoV-2 viral variants, including
the Delta variant.1-6
AstraZeneca will prepare regulatory submission of the prophylaxis
(PROVENT and STORM CHASER) data to health authorities for potential
emergency use authorisation or conditional approval of AZD7442.
Full results from PROVENT will be submitted for publication in a
peer-reviewed medical journal and presented at a forthcoming
medical meeting.
PROVENT
PROVENT is a Phase III, randomised, double-blind,
placebo-controlled, multi-centre trial assessing the safety and
efficacy of a single 300mg dose of AZD7442 compared to placebo for
the prevention of COVID-19. The trial was conducted in 87 sites in
the US, UK, Spain, France and Belgium. 5,197 participants were
randomised in a 2:1 ratio to receive a single intramuscular (IM)
dose of either 300mg of AZD7442 (n = 3460) or saline placebo (n =
1,737), administered in two separate, sequential IM
injections.
The primary efficacy endpoint was the first case of any SARS-CoV-2
RT-PCR positive symptomatic illness occurring post dose prior to
day 183. Subjects will continue to be followed for 15
months.
Participants were adults 18 years-old and over who would benefit
from prevention with the LAAB, defined as having increased risk for
inadequate response to active immunisation (predicted poor
responders to vaccines or intolerant of vaccine) or having
increased risk for SARS-CoV-2 infection, including those whose
locations or circumstances put them at appreciable risk of exposure
to the SARS-CoV-2 virus. Participants at the time of screening were
unvaccinated and had a negative point-of-care SARS-CoV-2 serology
test.
Approximately 43% of participants were 60 years and over. In
addition, more than 75% had baseline co-morbidities and other
characteristics that are associated with an increased risk for
severe COVID-19 should they become infected, including those with
immunosuppressive disease or taking immunosuppressive medications,
diabetes, severe obesity or cardiac disease, chronic obstructive
pulmonary disease, chronic kidney and chronic liver disease.
Approximately 73% were White/Caucasian, 17% Black/African American,
and 3% Asian. Approximately 15% of participants were
Hispanic.
AZD7442
AZD7442 is a combination of two LAABs - tixagevimab (AZD8895)
and cilgavimab (AZD1061) - derived from B-cells donated by
convalescent patients after SARS-CoV-2 virus. Discovered by
Vanderbilt University Medical Center and licensed
to AstraZeneca in June 2020, the human monoclonal antibodies
bind to distinct sites on the SARS-CoV-2 spike
protein7 and
were optimised by AstraZeneca with half-life extension and reduced
Fc receptor and complement C1q binding. The half-life extension
more than triples the durability of its action compared to
conventional antibodies and could afford up to 12 months of
protection from COVID-19 following a single
administration.8-11 The
reduced Fc receptor binding aims to minimise the risk of
antibody-dependent enhancement of disease - a phenomenon in which
virus-specific antibodies promote, rather than inhibit, infection
and/or disease.12
AZD7442 is being studied in a comprehensive clinical trial
programme for both prevention and treatment of COVID-19 in over
9,000 participants. Ongoing trials include TACKLE
COVID-1913,
a Phase III treatment trial in an outpatient setting and
collaborator treatment trials in outpatient and hospitalised
settings. AZD7442 is being assessed in both IM and intravenous
administration routes.
AZD7442 is being developed with support from the US Government,
including federal funds from the Department of Health and Human
Services; Office of the Assistant Secretary for Preparedness and
Response; Biomedical Advanced Research and Development Authority in
partnership with the Department of Defense; Joint Program Executive
Office for Chemical, Biological, Radiological and Nuclear Defense,
under Contract No. W911QY-21-9-0001.
AstraZeneca is working with governments around the world to make
AZD7442 accessible to high-risk populations as another valuable
option in the fight to end COVID-19, should it prove to be
effective and well tolerated.
Data published in Nature in
July 2020 showed that in preclinical experiments, the LAABs were
able to block the binding of the SARS-CoV-2 virus to host cells and
protect against infection in cell and animal models of
disease.14
Under the terms of the licensing agreement with Vanderbilt,
AstraZeneca will pay single-digit royalties on future net
sales.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery,
development, and commercialisation of prescription medicines in
Oncology, Rare Diseases, and BioPharmaceuticals, including
Cardiovascular, Renal & Metabolism, and Respiratory &
Immunology. Based in Cambridge, UK, AstraZeneca operates in over
100 countries and its innovative medicines are used by millions of
patients worldwide. Please visit astrazeneca.com and follow the
Company on Twitter @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1.
Liu C, et al. Reduced neutralization of
SARS-CoV-2 B.1.617 by vaccine and convalescent
serum. Cell. 2021 https://doi.org/10.1016/j.cell.2021.06.020
2.
Zhou D, et al. Evidence of escape
of SARS-CoV-2 variant B.1.351 from natural and vaccine induced
sera. Cell.
2021; doi: 10.1016/j.cell.2021.02.037.
3.
Dejnirattisai W, et al. Antibody evasion by the
Brazilian P.1 strain of SARS-CoV-2. bioRxiv.
2021; https://doi.org/10.1101/2021.03.12.435194.
4.
Wang P, Nair MS, Liu L. et al. Antibody
resistance of SARS-CoV-2 variants B.1.351 and
B.1.1.7. Nature 2021 Mar 8. doi: 10.1038/s41586-021-03398-2.
Epub ahead of print. PMID: 33684923.
5.
Chen RE, et al. Resistance of SARS-CoV-2 variants
to neutralization by monoclonal and serum-derived polyclonal
antibodies. Nat Med 2021; 27, 717-726.
https://doi.org/10.1038/s41591-021-01294-w.
6.
Wang P, et al. Increased resistance of SARS-CoV-2
variant P.1 to antibody neutralization. Cell
Host Microbe. 2021; 29 (5):
747-751.e4.
7.
Dong J, et al. Genetic and structural basis for
recognition of SARS-CoV-2 spike protein by a two-antibody
cocktail. bioRxiv. 2021; doi:
10.1101/2021.01.27.428529.
8.
Robbie GJ, et al. A novel investigational
Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an
extended half-life in healthy adults. Antimicrob Agents
Chemother. 2013; 57 (12):
6147-53.
9.
Griffin MP, et al. Safety, Tolerability, and
pharmacokinetics of MEDI8897, the respiratory syncytial virus
prefusion F-targeting monoclonal antibody with an extended
half-life, in healthy adults. Antimicrob Agents
Chemother. 2017; 61(3):
e01714-16.
10.
Yu XQ, et al. Safety, Tolerability, and
pharmacokinetics of MEDI4893, an investigational,
extended-half-life, anti-staphylococcus aureus alpha-toxin human
monoclonal antibody, in healthy adults. Antimicrob Agents
Chemother. 2016; 61 (1):
e01020-16.
11.
Domachowske JB, et al. Safety, tolerability and
pharmacokinetics of MEDI8897, an extended half-life single-dose
respiratory syncytial virus prefusion F-targeting monoclonal
antibody administered as a single dose to healthy preterm
infants. Pediatr Infect Dis
J. 2018; 37(9):
886-892.
12.
van Erp EA, et al. Fc-mediated antibody
effector functions during respiratory syncytial virus infection and
disease. Front
Immunol. 2019; 10:
548.
13.
Clinicaltrials.gov.
Phase III study of AZD7442 for treatment of COVID-19 in outpatient
adults (TACKLE). Available at:
https://clinicaltrials.gov/ct2/show//NCT04723394. [Last accessed:
30 June 2021].
14.
Zost SJ, et al. Potently neutralizing and
protective human antibodies against SARS-CoV
2. Nature. 2020; 584: 443-449.
Adrian Kemp
Company Secretary
AstraZeneca PLC
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
Date:
20 August 2021
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|