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 September 2022
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.
Evusheld positive CHMP opinion in EU
16
September 2022 07:05 BST
Evusheld long-acting
antibody combination recommended for approval
in the EU for the treatment of COVID-19
Recommendation based on TACKLE Phase III treatment data
showing
reduced risk of severe COVID-19 or death
AstraZeneca's Evusheld (tixagevimab and cilgavimab, formerly
AZD7442), a long-acting antibody combination, has been recommended
for marketing authorisation in the European Union (EU) for the
treatment of adults and adolescents (aged 12 years and older
weighing at least 40 kg) with COVID-19 who do not require
supplemental oxygen and who are at increased risk of progressing to
severe COVID-19.
The Committee for Medicinal Products for Human Use
(CHMP) of the European Medicines Agency based its positive opinion
on results from the TACKLE Phase III COVID-19 treatment trial which
showed one intramuscular (IM) dose of Evusheld provided clinically and
statistically significant protection against progression to severe
COVID-19 or death from any cause compared to
placebo. Evusheld treatment
earlier in the disease course led to more favourable outcomes.
TACKLE was conducted in non-hospitalised adults with
mild-to-moderate COVID-19 who were symptomatic for seven days or
less. 90%
of trial participants were at high risk of progression to severe
COVID-19 due to co-morbidities or age. Evusheld was
generally well tolerated in the trial.1
Michel Goldman, M.D., Ph.D., Professor, Institute
for Interdisciplinary Innovation in Healthcare, Université Libre de
Bruxelles, and former Executive Director of the European Innovative
Medicines Initiative, said: "Despite the remarkable efficacy of
COVID-19 vaccines in the overall population, patients with an
impaired immune system remain at very high risk to develop severe
COVID-19 requiring hospitalisation. For high-risk patients, there
is a major need for tolerable and effective therapies that can be
used to block COVID-19 progression and prevent poor outcomes. As we
head into the autumn and winter months when COVID-19 infections may
rise, Evusheld represents an important new treatment option
to protect patients infected with the SARS-CoV-2 virus against
severe disease and death."
Iskra Reic, Executive Vice President, Vaccines and
Immune Therapies, AstraZeneca, said: "Evusheld has already made an important difference
around the world helping prevent COVID-19 infections in vulnerable
populations who can't mount an adequate response to COVID-19
vaccination. This positive CHMP opinion
underscores Evusheld's potential as a COVID-19 treatment for
patients at increased risk of progressing to severe
disease."
The recommended dose of Evusheld for treatment in the EU is 300mg of
tixagevimab and 300mg of cilgavimab, administered as two separate,
sequential IM injections.
Evusheld been
shown to retain in vitro neutralisation of Omicron BA.5, which is
currently the dominant SARS-CoV-2 variant in
Europe.2 Real-world
evidence generated to date has demonstrated significantly lower
rates of symptomatic COVID-19 and/or hospitalisation/death for
immunocompromised patients receiving Evusheld compared to control arms. This includes
real-world evidence collected while Omicron BA.5, BA.4, BA.2, BA.1
and BA.1.1 were circulating.3-6
Evusheld was
granted marketing
authorisation in the EU for
pre-exposure prophylaxis (prevention) of COVID-19 in a broad
population of adults and adolescents earlier this year and is
already available in a majority of countries in
Europe.
AstraZeneca
anticipates that the European Commission will shortly complete its
review of the CHMP positive opinion to determine whether to grant
marketing authorisation for treatment of COVID-19 in appropriate
populations.
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 Evusheld (300mg each of cilgavimab and tixagevimab)
compared to placebo for the treatment of mild-to-moderate COVID-19.
The trial was conducted in 95 sites in the US, Latin America,
Europe and Japan. 903 participants were randomised (1:1) to receive
either Evusheld (n = 452) or saline placebo (n = 451),
administered in two separate, sequential IM
injections.
Participants
were adults 18 years-old and over who had mild-to-moderate COVID-19
and were 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 1.
Participants were not vaccinated against COVID-19 at the time of
screening.
Detailed results from the TACKLE trial published
in The
Lancet Respiratory Medicine showed Evusheld significantly
reduced the relative risk of progressing to severe COVID-19 or
death (from any cause) by 50% (95% confidence interval [CI] 15, 71;
p=0.010) through day 29 compared to placebo in non-hospitalised
patients with mild-to-moderate COVID-19 who were symptomatic for
seven days or less, the trial's primary endpoint. In pre-specified
analyses of participants who received treatment within three days
of symptom onset, Evusheld reduced the risk of developing severe
COVID-19 or death (from any cause) by 88% compared to placebo (95%
CI 9, 98), and the risk reduction was 67% (95% CI 31, 84) compared
with placebo when participants received Evusheld within five days of symptom
onset.1
Evusheld was
generally well tolerated in the trial. Adverse events (AEs)
occurred more frequently in the placebo group (163/451; 36%) than
the Evusheld group (132/452; 29%). The most common AE was
COVID-19 pneumonia, occurring in 49 participants (11%) in the
placebo group and 26 participants (6%) in
the Evusheld group. Serious AEs occurred in 54
participants (12%) in the placebo group and 33 participants (7%) in
the Evusheld group. There were six COVID-19-reported
deaths in the placebo group and three in
the Evusheld group.1
Evusheld
Evusheld, formerly known as AZD7442, is a combination of
two long-acting antibodies - tixagevimab
(AZD8895) and cilgavimab (AZD1061) - derived from B-cells donated
by convalescent patients after SARS-CoV-2 infection. 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
reduction of Fc effector function and
complement C1q binding.8 The
half-life extension more than triples the durability of its action
compared to conventional antibodies;9-11 data
from the PROVENT Phase III trial show protection lasting six
months.12 The
reduced Fc effector function 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.13
Evusheld is
authorised for use for pre-exposure prophylaxis (prevention) of
COVID-19 in the US (emergency use), EU, Japan and many other
countries. Evusheld is approved for treatment of those with risk
factors for severe SARS-CoV-2 infection in Japan. Regulatory
submissions are progressing for both prevention and treatment
indications around the world.
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.
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. Montgomery H, et al. Efficacy and
Safety of Intramuscular Administration of AZD7442
(Tixagevimab/Cilgavimab) for Early Outpatient Treatment of
COVID-19: The TACKLE Phase 3 Randomised Controlled
Trial. Lancet Respir
Med. Published online June 7,
2022. doi.org/10.1016/S2213-2600(22)00180-1
2. US Food and Drug
Administration. Fact Sheet for Healthcare Providers: Emergency Use
Authorization for Evusheld™(Tixagevimab Co-Packaged with
Cilgavimab). Available at: https://www.fda.gov/media/154701/download
[Last accessed: September 2022]
3. Jurdi
A, et al. Tixagevimab/Cilgavimab
Pre-Exposure Prophylaxis Is Associated with Lower Breakthrough
Infection Risk in Vaccinated Solid Organ Transplant Recipients
during the Omicron Wave. American
Journal of Transplantation. Published online June 21, 2022.
doi:10.1111/AJT.17128
4. Kertes J, et al. Association
between AZD7442 (Tixagevimab-Cilgavimab) Administration and
SARS-CoV-2 Infection, Hospitalization and
Mortality. Clinical Infectious
Diseases. Published online July
29, 2022. doi:10.1093/CID/CIAC625
5. Young-Xu Y, et al.
Tixagevimab/Cilgavimab for Prevention of COVID-19 during the
Omicron Surge: Retrospective Analysis of National VA Electronic
Data. medRxiv. Published online May 29,
2022:2022.05.28.22275716.
doi:10.1101/2022.05.28.22275716
6.
AstraZeneca Data on File.
7. Dong J, et al. Genetic and
Structural Basis for SARS-CoV-2 Variant Neutralization by a
Two-Antibody Cocktail. Nat
Microbiol.
2021;6(10):1233-1244
8. Loo YM, et al. AZD7442 Demonstrates
Prophylactic and Therapeutic Efficacy in Non-Human Primates and
Extended Half-Life in Humans. Sci Transl
Med.
2022;14(635):eabl8124
9. Robbie GJ, et al. A Novel
Investigational Fc-Modified Humanized Monoclonal Antibody,
Motavizumab-YTE, Has an Extended Half-Life in Healthy
Adults. Antimicrobial Agents and
Chemotherapy.
2013;57(12):6147-6153
10. 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)
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. Levin
MJ, et al. Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for
Prevention of Covid-19. N Engl J
Med.
2022;386(23):2188-2200
13. van
Erp, EA et al. Fc-Mediated
Antibody Effector Functions During Respiratory Syncytial Virus
Infection and Disease. Front
Immunol.
2019;10(MAR)
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:
16 September 2022
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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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