a0538v
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 December
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
9 December 2021 07:00 GMT
Evusheld (formerly AZD7442) long-acting antibody
combination
authorised for emergency use in the US for pre-exposure prophylaxis
(prevention) of COVID-19
Only antibody therapy authorised in US for pre-exposure prophylaxis
Pivotal phase III data showed robust efficacy and long-term
protection with one dose in high-risk population
AstraZeneca's Evusheld (tixagevimab co-packaged with cilgavimab), a
long-acting antibody (LAAB) combination, has received emergency use
authorisation (EUA) in the US for the pre-exposure prophylaxis
(prevention) of COVID-19, with
first doses expected to become available very
soon.
The Food and Drug Administration (FDA) granted the EUA
for Evusheld for pre-exposure prophylaxis of COVID-19 in
adults and adolescents (aged 12 and older who weigh 40kg or more)
with moderate to severe immune compromise due to a medical
condition or immunosuppressive medications and who may not mount an
adequate immune response to COVID-19 vaccination, as well as those
individuals for whom COVID-19 vaccination is not recommended.
Recipients should not be currently infected with or had recent
known exposure to a person infected with
SARS-CoV-2.
Myron J. Levin, MD, Professor of Pediatrics and Medicine,
University of Colorado School of Medicine, US, and principal
investigator on the PROVENT trial, said: "Millions of people in the
US and around the world remain at serious risk for COVID-19 because
their immune systems do not generate a sufficient immune response,
even after receiving all recommended doses of vaccine. I am excited
to offer my patients Evusheld as an easily-administered new option that
provides long-lasting protection that could help them return to
their everyday lives."
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, AstraZeneca, said: "We are proud to play a leading role in
fighting the COVID-19 pandemic and, with Evusheld, we now have the first antibody therapy
authorised in the US to prevent COVID-19 symptoms before virus
exposure, while also providing long lasting protection with a
single dose. Evusheld neutralises all previous SARs-CoV-2 variants
to date, and we are working quickly to establish its efficacy
against the new Omicron variant. We thank our clinical trial
participants, the investigators, scientists, and government
agencies and our colleagues at AstraZeneca who have all contributed
to the development of Evusheld."
Brian Koffman, MDCM (retired), MS Ed, Co-Founder, Executive Vice
President and Chief Medical Officer of the CLL (Chronic Lymphocytic
Leukemia) Society, US, said: "One of the primary questions I keep
getting asked by patients is 'When can I hug my grandchildren
again?' As a physician and person with a weakened immune system, l
am filled with hope now that Evusheld will soon be available to those who can't
count on vaccination alone to provide the protection they
need."
Evusheld is a combination
of two long-acting monoclonal antibodies and is the only antibody
therapy authorised in the US for COVID-19 pre-exposure prophylaxis
and the only COVID-19 antibody delivered as an intramuscular dose
(150mg tixagevimab and 150mg cilgavimab).
About 2% of the global population is considered at
increased risk of an inadequate response to a COVID-19
vaccine.1,2 About
seven million people in the US are immunocompromised and may
benefit from Evusheld for pre-exposure prophylaxis of
COVID-19.1,3,4 This
includes people with blood cancers or other cancers being treated
with chemotherapy, and those taking medications after an organ
transplant or who are taking immunosuppressive drugs for conditions
including multiple sclerosis and rheumatoid
arthritis.5-9
The primary data supporting the Evusheld EUA are from the ongoing PROVENT Phase III
pre-exposure prevention trial, which showed a statistically
significant reduction (77% at primary analysis, 83% at median
six-month analysis) in the risk of developing symptomatic COVID-19
compared to placebo, with protection from the virus continuing for
at least six months. More follow-up is needed to establish the full
duration of protection provided by Evusheld. Data from the Phase III STORM CHASER
post-exposure trial and the Evusheld Phase I trial also supported the
EUA. Evusheld was well-tolerated in the
trials.
Evusheld and SARS-CoV-2 variants
Studies are underway to provide information on the impact of the
new Omicron variant (B.1.1.529) on Evusheld. 10,11 Of
the Omicron binding site substitutions relevant
to Evusheld that have been tested to date in preclinical
assays, none have been associated with escape
from Evusheld neutralisation.10,11 In
vitro findings
demonstrate Evusheld neutralises other recent emergent SARS-CoV-2
viral variants, including the Delta and Mu
variants.10
Evusheld 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 has agreed to supply the US government with 700,000
doses of Evusheld. The U.S. government has indicated that it plans
to distribute these doses to states and territories at no cost and
on a pro rata basis.
AstraZeneca is progressing with filings around the globe for
potential emergency use authorisation or conditional approval
of Evusheld in both COVID-19 prophylaxis and
treatment.
Notes
Evusheld
Evusheld, formerly known as 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
protein13 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;14-16 data
from the Phase III PROVENT trial show protection lasting at least
six months.17 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.18 Evusheld is
delivered as an IM dose of 150mg tixagevimab and 150mg cilgavimab
administered in two separate, consecutive
injections.
In August 2021, AstraZeneca announced that Evusheld demonstrated
a statistically significant reduction in the risk of developing
symptomatic COVID-19 in the PROVENT trial; efficacy was 83%
compared to placebo in a six-month
analysis announced on
18 November 2021. In October 2021,
AstraZeneca announced positive
high-level results from the Evusheld TACKLE Phase III outpatient treatment
trial. Evusheld 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.
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.
Oliver, S MD. Data and clinical
considerations for additional doses in immunocompromised people.
ACIP Meeting July 22, 2021. Available at: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-07/07-COVID-Oliver-508.pdf.
[Last accessed: December 2021].
2.
AstraZeneca
data on file.
3.
Taken
as percentage of U.S Population: 328.2m (2019).
4.
CDC:
Lower range: adult pneumococcal vaccine (~25% ), mid range: flu
(~48%), upper range: COVID vaccine (~70%).
5.
Centers for Disease Control and
Prevention. Altered Immunocompetence. General Best Practice
Guideline for Immunization: Best Practices Guidance of the Advisory
Committee on Immunization Practices. [Online]. Available
at: https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/immunocompetence.html.
[Last accessed: December 2021].
6.
Boyarsky BJ, et al. Immunogenicity of a Single
Dose of SARS-CoV-2 Messenger RNA Vaccine in Solid Organ Transplant
Recipients. JAMA. 2021; 325
(17):1784-1786.
7.
Rabinowich L, et al. Low immunogenicity to
SARS-CoV-2 vaccination among liver transplant
recipients, Journal of
Hepatology (2021). doi:
https://doi.org/10.1016/ j.jhep.2021.04.020.
8.
Deepak
P, et al. Glucocorticoids and B Cell Depleting Agents Substantially
Impair Immunogenicity of mRNA Vaccines to SARS-CoV-2. medRxiv
[Preprint]. 2021 Apr 9:2021.04.05.21254656. doi:
10.1101/2021.04.05.21254656. PMID: 33851176; PMCID:
PMC8043473.
9.
Simon D, et al. SARS-CoV-2 vaccination responses
in untreated, conventionally treated and anticytokine-treated
patients with immune-mediated inflammatory
diseases. Ann Rheum
Dis. 2021 May 6:
annrheumdis-2021-220461. doi: 10.1136/annrheumdis-2021-220461. Epub
ahead of print. PMID: 33958324.
10.
ACTIV. National Center for
Advancing Translational Sciences Open Data Portal. SARS-CoV-2
Variants & Therapeutics, All Variants Reported in vitro
Therapeutic Activity. Available at: https://opendata.ncats.nih.gov/variant/activity.
[Last accessed: December 2021].
11.
Bloom
Labs. Available from:
1.
https://twitter.com/jbloom_lab/status/1464005705891868702/photo/1 [Last
accessed December 2021].
12.
AstraZeneca
data on file.
13.
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.
14.
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.
15.
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.
16.
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.
17.
AstraZeneca news release. New
analyses of two AZD7442 COVID-19 trials in high-risk populations
confirm robust efficacy and long-term prevention. Available
at: https://www.astrazeneca.com/media-centre/press-releases/2021/new-analyses-of-two-azd7442-covid-19-phase-iii-trials-in-high-risk-populations-confirm-robust-efficacy-and-long-term-prevention.html.
[Last accessed: December 2021]
18.
van Erp EA, et al. Fc-mediated antibody
effector functions during respiratory syncytial virus infection and
disease. Front
Immunol. 2019; 10:
548.
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:
9 December
2021
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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