a6168x
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 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 approved for COVID-19 in Japan
30 August 2022 13:00 BST
Evusheld long-acting
antibody combination approved
for prevention and treatment of COVID-19 in Japan
First global approval for Evusheld as a COVID-19
treatment
PROVENT Phase III prevention trial showed reduced risk
of developing symptomatic COVID-19
TACKLE Phase III treatment trial showed reduced risk
of severe COVID-19 or death in high-risk patients
AstraZeneca's Evusheld (tixagevimab and cilgavimab, formerly
AZD7442), a long-acting antibody combination, has been approved in
Japan for both prevention (pre-exposure prophylaxis) and treatment
of symptomatic disease caused by SARS-CoV-2 infection. The decision
marks the first global marketing approval
for Evusheld as a treatment for
COVID-19.
In prevention, Japan's
Ministry of Health, Labour and Welfare (MHLW) granted Evusheld Special
Approval for Emergency for
adults and adolescents (12
years of age and older weighing at least
40kg). Evusheld is approved for use in those
whom SARS-CoV-2
vaccination is not recommended and who may have an inadequate
response to a COVID-19 vaccine due to immunodeficiencies.
Recipients of Evusheld for prevention should
not be currently infected with or have had recent known exposure to
a person infected with SARS-CoV-2.
In treatment, Evusheld is approved for adults and
adolescents (12
years of age and older weighing at least 40kg) with
risk factors for severe SARS-CoV-2 infection who do not require
supplemental oxygen.
Kazuhiro Tateda, M.D. Ph.D., Professor, Department of Microbiology
and Infectious Disease, Toho University, Tokyo, Japan, said:
"COVID-19 continues to have a significant impact on our daily lives
in Japan. Many people, including older adults, patients with
comorbidities, and immunocompromised patients, remain at risk for
poor outcomes from severe COVID-19. Evusheld will
be a much-needed new option, offering long-term protection for
those who do not achieve an adequate immune response after
vaccination and helping prevent severe disease and death in those
who do become infected."
Itaru Matsumura, M.D., Ph.D. Professor & Chairman, Department
of Hematology & Rheumatology, Kindai University Faculty of
Medicine, Otsuka, Japan, said: "Despite the progress of
vaccinations and stringent safety precautions, there are very large
number of new infections in Japan. The approval
of Evusheld is expected to provide a non-vaccine
prophylactic option for those who cannot expect a full immune
response from COVID-19 vaccination, such as patients with blood
cancers."
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, AstraZeneca, said: "The
approvals of Evusheld in Japan represent an important milestone in
our ongoing efforts to help combat COVID-19 on all
fronts. Evusheld is
now the only long-acting antibody combination authorised for both
COVID-19 prevention and treatment, allowing us to help protect even
more vulnerable patients such as the immunocompromised from this
devastating disease."
The Japanese government has agreed to purchase 300,000 units
of Evusheld (150mg each of tixagevimab and cilgavimab),
and AstraZeneca is working with the government and partners to make
first doses available as soon as possible.
The approvals were based on efficacy and safety data from
the Evusheld clinical development programme, including
the PROVENT Phase III pre-exposure prophylaxis trial, the TACKLE
Phase III outpatient treatment trial, and Phase I trials, including
in Japan. In
PROVENT, a 300mg intramuscular (IM) dose
of Evusheld significantly
reduced the risk of developing symptomatic COVID-19 by 77% (95%
confidence interval (CI): 46, 90; p<0.001) COVID-19 compared to
placebo at the primary analysis.1 An
83% (95% CI: 66, 91) relative risk reduction was shown at a
six-month median follow-up analysis, with protection from the virus
lasting six months.1
In TACKLE, a 600mg IM dose of 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.2 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) when participants received Evusheld within five days of symptom
onset.2
Evusheld was
generally well-tolerated in the trials.1,2
The recommended dose for prevention of symptomatic disease caused
by SARS-CoV-2 infection in Japan is 150mg of tixagevimab and 150mg
of cilgavimab, administered as separate sequential IM
injections. Depending on the prevalence of SARS-CoV-2
variants, 300mg of tixagevimab and 300mg of cilgavimab may be
administered for prevention. The recommended dose for
treatment of COVID-19 is 300mg of tixagevimab and 300mg of
cilgavimab, administered as separate sequential IM
injections.
Evusheld has
been shown to retain in vitro neutralisation activity against the main
Omicron variants currently circulating globally, including BA.5 and
BA.2.3,4
Evusheld is
also authorised for use for pre-exposure prophylaxis (prevention)
of COVID-19 in the US (emergency use), EU and many other countries.
Regulatory submissions are progressing for both prevention and
treatment indications around the world.
Notes
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 protein5 and
were optimised by AstraZeneca with half-life extension and
reduction of Fc effector function and
complement C1q binding.6 The
half-life extension more than triples the durability of its action
compared to conventional antibodies;7-9 data
from the PROVENT Phase III trial show protection lasting six
months.1 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.10
The primary data supporting the Evusheld pre-exposure prophylaxis authorisations are
from the ongoing PROVENT
Phase III pre-exposure prevention trial, published
in The
New England Journal of Medicine, 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 lasting six
months.1 More
than 75% of PROVENT participants at baseline had co-morbidities
that put them at high risk for severe COVID-19 if they were to
become infected, including people who are immunocompromised and may
have an inadequate immune response to COVID-19
vaccination.
Detailed results from the TACKLE Phase III outpatient treatment
trial, published in The
Lancet Respiratory Medicine,
showed Evusheld provided clinically and statistically
significant protection against progression to severe COVID-19 or
death from any cause compared to placebo, with treatment
with Evusheld earlier in the disease course leading to
more favourable outcomes.2 TACKLE
was conducted in non-hospitalised adults with mild-to-moderate
COVID-19 who were symptomatic for seven days or less. 90% of
participants were at high risk of progression to severe COVID-19
due to age or co-morbidities, including cancer, diabetes, obesity,
chronic lung disease or asthma, cardiovascular disease or
immunosuppression.
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. Levin
MJ, et al. Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for
Prevention of Covid-19. N Engl J
Med.
2022;386(23):2188-2200
2. 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
3. US Food and Drug
Administration FACT SHEET FOR HEALTHCARE PROVIDERS: EMERGENCY USE
AUTHORIZATION FOR EVUSHELDTM (Tixagevimab
Co-Packaged with Cilgavimab). Available at: https://www.fda.gov/media/154701/download [Last
accessed: August 2022]
4. Vector Engineering
Lab et al. COVID CG. Available at: https://covidcg.org/ [Last
accessed: August 2022]
5. 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
6. 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
7. 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
8. 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)
9. 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
10. 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:
30 August 2022
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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