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 October
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 PhIII trial positive in COVID outpatients
11 October 2021 07:00 BST
AZD7442 reduced risk of developing severe COVID-19 or
death
in TACKLE Phase III outpatient treatment trial
Trial met primary endpoint
AZD7442 is the only long-acting antibody combination
shown
to both prevent and treat COVID-19
Positive high-level results from the TACKLE Phase III COVID-19
treatment trial showed AstraZeneca's AZD7442, a long acting
antibody (LAAB) combination, achieved a statistically significant
reduction in severe COVID-19 or death compared to placebo in
non-hospitalised patients with mild-to-moderate symptomatic
COVID-19.
A total of 90% of participants enrolled were from populations at
high risk of progression to severe COVID-19, including those with
co-morbidities.
The trial met the primary endpoint, with a dose of 600mg of AZD7442
given by intramuscular (IM) injection reducing the risk of
developing severe COVID-19 or death (from any cause) by 50%
compared to placebo in outpatients who had been symptomatic for
seven days or less. The trial recorded 18 events in the AZD7442 arm
(18/407) and 37 in the placebo arm (37/415). The LAAB was generally
well tolerated in the trial.
In a prespecified analysis of participants who received treatment
within five days of symptom onset, AZD7442 reduced the risk of
developing severe COVID-19 or death (from any cause) by 67%
compared to placebo, with nine events in the AZD7442 arm (9/253)
and 27 in the placebo arm (27/251).
AZD7442 is the first LAAB with Phase III data to demonstrate
benefit in both prophylaxis and treatment of COVID-19 and is easily
administered by IM injection.
Hugh Montgomery, Professor of Intensive Care Medicine at University
College London, and TACKLE principal investigator, said: "With
continued cases of serious COVID-19 infections across the globe,
there is a significant need for new therapies like AZD7442 that can
be used to protect vulnerable populations from getting COVID-19 and
can also help prevent progression to severe disease. These positive
results show that a convenient intramuscular dose of AZD7442 could
play an important role in helping combat this devastating
pandemic."
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, AstraZeneca, said: "These important results for AZD7442,
our long-acting antibody combination, add to the growing body of
evidence for use of this therapy in both prevention and treatment
of COVID-19. An early intervention with our antibody can give a
significant reduction in progression to severe disease, with
continued protection for more than six months."
TACKLE included 903 participants in a 1:1 randomisation
AZD7442 to placebo. The primary analysis was based on 822
participants.
AstraZeneca will be discussing the data with health authorities. On
5 October 2021, the Company announced that it had
submitted a request to the US Food and Drug Administration for
Emergency Use Authorisation for AZD7442 for prophylaxis of
COVID-19.
Full results from TACKLE will be submitted for publication in a
peer-reviewed medical journal and presented at a forthcoming
medical meeting.
Notes
TACKLE
TACKLE is a Phase III, randomised, double-blind,
placebo-controlled, multi-centre trial assessing the safety and
efficacy of a single 600mg IM dose of AZD7442 compared to placebo
for the outpatient treatment of COVID-19. The trial was conducted
in 96 sites in Brazil, Czech Republic, Germany, Hungary,
Italy, Japan, Mexico, Poland, Russian Federation, Spain, Ukraine,
UK and US. 903 participants were randomised (1:1) to receive either
AZD7442 (n = 452) or saline placebo (n = 451), administered in two
separate, sequential IM injections.
Participants were adults 18 years-old and over who were
non-hospitalised with mild-to-moderate COVID-19 and symptomatic for
seven days or less. Participants had a documented
laboratory-confirmed SARS-CoV-2 infection, as determined by a
molecular test (antigen or nucleic acid) from any respiratory tract
specimen (e.g. oropharyngeal, nasopharyngeal, or nasal swab or
saliva) collected no more than three days prior to day
one.
The primary efficacy endpoint was the composite of either severe
COVID-19 or death from any cause through day 29. Subjects will
continue to be followed for 15 months.
Approximately 13% of participants were 65 years and over. In
addition, 90% had baseline co-morbidities and other characteristics
that put them at high risk of progression to severe COVID-19,
including cancer, diabetes, obesity, chronic lung disease or
asthma, cardiovascular disease or immunosuppression. Approximately
62% were White/Caucasian, 4% Black/African-American, 6% Asian and
24% American Indian or Alaskan Native. Approximately 52% of
participants were Hispanic/Latino.
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
protein1 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
administration2-4;
data from the Phase I trial show high neutralising antibody titres
for at least nine months.5 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.6
In August 2021, AstraZeneca announced AZD7442
demonstrated a statistically significant reduction in the risk of
developing symptomatic COVID-19 in the PROVENT Phase III
pre-exposure prevention trial.
AZD7442 is also being studied as a potential treatment for
hospitalised COVID-19 patients as part of the National Institute of
Health's ACTIV-3
trial and
in an additional collaborator hospitalisation treatment
trial.
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.
In preclinical experiments, data show 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.7 Additional in
vitro findings demonstrate
AZD7442 neutralises recent emergent SARS-CoV-2 viral variants,
including the Delta and Mu variants.8
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. 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.
2. 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.
3. 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.
4. 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.
5. Loo Y-M, et al.
AZD7442 demonstrates prophylactic and therapeutic efficacy in
non-human primates and extended half-life in humans. medRxiv. Cold
Spring Harbor Laboratory Press; 2021 [preprint] Available
from: https://www.medrxiv.org/content/10.1101/2021.08.30.21262666v1.
6. van Erp EA, et
al. Fc-mediated antibody effector functions during respiratory
syncytial virus infection and disease. Front
Immunol. 2019; 10:
548.
7. Zost SJ, et al. Potently
neutralizing and protective human antibodies against SARS-CoV
2. Nature. 2020; 584: 443-449.
8.
ACTIV. National Center for Advancing Translational Sciences
OpenData Portal. SARS-CoV-2 Variants & Therapeutics, All
Variants Reported in vitro Therapeutic Activity. Available at:
https://opendata.ncats.nih.gov/variant/activity [Last accessed:
September 2021].
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:
11 October
2021
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By: /s/
Adrian Kemp
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Name:
Adrian Kemp
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Title:
Company Secretary
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