REG - AstraZeneca PLC - Evusheld approved in the EU for COVID-19

AstraZenecaAnnouncement

28/03/2022 07:00

For best results when printing this announcement, please click on link below:
http://newsfile.refinitiv.com/getnewsfile/v1/story?guid=urn:newsml:reuters.com:20220328:nRSb1552Ga&default-theme=true

RNS Number : 1552G  AstraZeneca PLC  28 March 2022

28 March 2022 07:00 BST

 

Evusheld long-acting antibody combination approved in the EU for

pre-exposure prophylaxis (prevention) of COVID-19 in a broad population

 

Evusheld significantly reduced the risk of developing symptomatic COVID-19 in
PROVENT Phase III trial, with protection lasting at least six months

 

Evusheld retains neutralising activity against the Omicron BA.2 subvariant,

now the dominant strain in Europe

 

AstraZeneca's Evusheld (tixagevimab co-packaged with cilgavimab), a
long-acting antibody combination, has been granted marketing authorisation in
the European Union (EU) for the pre-exposure prophylaxis (prevention) of
COVID-19 in a broad population of adults and adolescents aged 12 years and
older weighing at least 40 kg.

 

The approval by the European Commission was based on results from the Evusheld
clinical development programme, including data from the PROVENT Phase III
pre-exposure prophylaxis trial which showed a 77% reduction in the risk of
developing symptomatic COVID-19 compared to placebo at the primary analysis
and an 83% reduction at a six-month median analysis, with protection from the
virus lasting at least six months.(1-3) Evusheld was generally well-tolerated
in the trial.(1-3)

 

Christoph D. Spinner, MD, Consulting Physician Infectious Diseases and
Pandemic Officer at the University Hospital Rechts der Isar and adjunct
teaching professor at the Technical University of Munich, Munich, Germany,
said: "Increasing COVID-19 cases, driven by the highly-transmissible BA.2
subvariant, and withdrawal of several pandemic public health measures make it
important to protect vulnerable populations, such as the immunocompromised,
from SARS-CoV-2 infection. The authorisation of Evusheld for a broad
population will allow health authorities in the EU to identify the populations
who are most at-risk and need additional protection."

 

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D,
AstraZeneca, said: "The EU approval represents an important milestone in our
efforts to help prevent COVID-19, and we will continue to work with
governments across Europe to make Evusheld available as quickly as possible.
Evusheld has the potential to provide long-lasting protection against COVID-19
for a broad population of individuals, including those who aren't adequately
protected by a COVID-19 vaccine, as well as those at increased risk of
exposure."

 

The recommended dose of Evusheld in Europe is 150mg of tixagevimab and 150mg
of cilgavimab, administered as two separate sequential intramuscular (IM)
injections.

 

There is a growing body of evidence from multiple independent in vitro and in
vivo (animal model) studies supporting the potential of Evusheld to protect
against the BA.1, BA.1.1 and BA.2 Omicron SARS-CoV-2 subvariants in
circulation around the world.(4-6) New data
(https://www.biorxiv.org/content/10.1101/2022.03.17.484787v1) from Washington
University School of Medicine demonstrated Evusheld retained potent
neutralising activity against the emerging and highly transmissible BA.2
subvariant, which is the dominant strain in many European countries and
currently accounts for over 60% of COVID-19 infections in Europe.(6,7)  This
study also showed Evusheld reduced viral burden and limited inflammation in
the lungs (in vivo) across all Omicron variants.(6)

 

Evusheld is authorised for emergency use for pre-exposure prophylaxis of
COVID-19 in the US and has been granted conditional marketing authorisation by
the Medicines and Healthcare products Regulatory Agency (MHRA) in Great
Britain for pre-exposure prophylaxis of COVID-19. Additionally, there are a
number of countries across Europe that have agreements in place to provide
Evusheld.

 

People who are not adequately protected by a COVID-19 vaccine may particularly
benefit from pre-exposure prophylaxis with Evusheld.(8-12) This population
includes about three million people in the EU who are immunocompromised such
as people with cancer or transplant patients or anyone taking
immunosuppressive medicines.(13) People at increased risk of exposure to the
SARS-CoV-2 virus could also benefit from protection with Evusheld.(14)

 

Evusheld is the only long-acting antibody combination with positive Phase III
data in the prevention and treatment of COVID-19.(2,15) AstraZeneca is
progressing with filings around the globe for potential emergency use
authorisation or marketing approval of Evusheld in both COVID-19 prophylaxis
and treatment.

 

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
(https://www.astrazeneca.com/media-centre/articles/2020/advancing-our-discovery-of-novel-coronavirus-neutralising-antibodies-against-covid-19.html)
, the human monoclonal antibodies bind to distinct sites on the SARS-CoV-2
spike protein(16) and were optimised by AstraZeneca with half-life extension
and reduction of Fc effector function. The half-life extension more than
triples the durability of its action compared to conventional
antibodies;(17-19) data from the PROVENT Phase III trial show protection
lasting at least six months.(1,3) 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.(20)

 

Evusheld has been granted marketing authorisation in the European Union and
Great Britain for pre-exposure prophylaxis (prevention) of COVID-19. In the
United States, Evusheld is authorised for emergency use for pre-exposure
prophylaxis of COVID-19 in people 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 due to a history
of severe adverse reaction to a COVID-19 vaccine. This population 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.(1) It is also authorised for use and being supplied in
several other countries around the world.

 

The primary data supporting the Evusheld authorisations are from the ongoing
PROVENT Phase III pre-exposure prevention trial,
(https://www.astrazeneca.com/media-centre/press-releases/2021/azd7442-prophylaxis-trial-met-primary-endpoint.html)
which showed a statistically significant reduction in the risk of developing
symptomatic COVID-19 compared to placebo, with protection from the virus
continuing for at least six months (77% at primary analysis [8/3441 (0.2%)
Evusheld arm, 17/1731 (1.0%) placebo arm]; 83% at median six month analysis
[11/3441 (0.3%) Evusheld arm, 31/1731 (1.8%) placebo arm]).(1-3) Follow-up is
ongoing to establish the full duration of protection provided by Evusheld.

 

In October 2021, AstraZeneca announced positive high-level results from the
TACKLE Phase III outpatient treatment trial
(https://www.astrazeneca.com/media-centre/press-releases/2021/azd7442-phiii-trial-positive-in-covid-outpatients.html#:~:text=The%20trial%20met%20the%20primary,for%20seven%20days%20or%20less.)
in which a 600mg IM dose of Evusheld was generally well-tolerated. AstraZeneca
is discussing the TACKLE mild-to-moderate COVID-19 treatment data with health
authorities.

 

Evusheld was generally well-tolerated in the trials.

 

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 (https://astrazeneca.com) and follow the Company
on Twitter @AstraZeneca
(https://twitter.com/AstraZeneca?ref_src=twsrc%5Egoogle%7Ctwcamp%5Eserp%7Ctwgr%5Eauthor)
.

 

Contacts

For details on how to contact the Investor Relations Team, please click here
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

References

1.   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
(https://www.fda.gov/media/154701/download)  [Last accessed March 2022].

2.   AstraZeneca news release. AZD7442 PROVENT Phase III prophylaxis trial
met primary endpoint in preventing COVID-19. Available at:
https://www.astrazeneca.com/media-centre/press-releases/2021/azd7442-prophylaxis-trial-met-primary-endpoint.html
(https://www.astrazeneca.com/media-centre/press-releases/2021/azd7442-prophylaxis-trial-met-primary-endpoint.html)
[Last accessed: March 2022].

3.   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
(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: March 2022]

4.   Dejnirattisai W, et al. SARS-CoV-2 Omicron-B.1.1.529 leads to
widespread escape from neutralizing antibody responses. Cell.
2022;185(3):467-484.e15.

5.   VanBlargan LA, et al. An infectious SARS-CoV-2 B.1.1.529 Omicron virus
escapes neutralization by therapeutic monoclonal antibodies. Nature Medicine.
2022; 28:490-495.

6.   Case, J et al. Resilience of S309 and AZD7442 monoclonal antibody
treatments against infection by SARS-CoV-2 Omicron lineage strains. Available
at: https://www.biorxiv.org/content/10.1101/2022.03.17.484787v1
(https://www.biorxiv.org/content/10.1101/2022.03.17.484787v1) [Last accessed
March 2022].

7.   COVID CG. (2022). GISAID. Available at:
https://covidcg.org/?groupKey=lineage®ion=Europe&residueCoordinates=1%2C1274&selectedGene=S&tab=group [Last
accessed: March 2022].

8.   Centers for Disease Control and Prevention. Altered Immunocompetence.
General Best Practice Guideline for Immunization: Best Practices Guidance of
the Advisory Committee on Immunization Practices. Available at:
https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/immunocompetence.html
(https://urldefense.com/v3/__https:/www.cdc.gov/vaccines/hcp/acip-recs/general-recs/immunocompetence.html__;!!Gajz09w!RwQfiAYQzYlOeTSOioWbipa_8JF-ZJ3KJiq3YvkLYGHSi1i_WNfqBuQD8qpdCfRMM3mO$)
[Last accessed: March 2022]

9.   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.

10.  Rabinowich L, et al. Low immunogenicity to SARS-CoV-2 vaccination among
liver transplant recipients. J Hepatol. 2021; 75(2):435-438.

11.  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.

12.  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; 80(10):1312-1316.

13.  AstraZeneca Data on File.

14.  Centers of Disease Control and Prevention. Risk Factors of Exposure to
COVID-19: Racial and Ethnic Health Disparities. 2020. Available from:
https://www.cdc.gov/coronavirus/2019-ncov/community/health-equity/racial-ethnic-disparities/increased-risk-exposure.html
(https://urldefense.com/v3/__https:/www.cdc.gov/coronavirus/2019-ncov/community/health-equity/racial-ethnic-disparities/increased-risk-exposure.html__;!!Gajz09w!RwQfiAYQzYlOeTSOioWbipa_8JF-ZJ3KJiq3YvkLYGHSi1i_WNfqBuQD8qpdCdTS4NOk$)
. [Last accessed: March 2022].

15.  AstraZeneca news release. Evusheld reduced risk of developing severe
COVID-19 or death in TACKLE Phase III outpatient treatment trial. Available
at:
https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/
(https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/azd7442-phiii-trial-positive-in-covid-outpatients.html)
Evusheld
(https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/azd7442-phiii-trial-positive-in-covid-outpatients.html)
-phiii-trial-positive-in-covid-outpatients.html
(https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/azd7442-phiii-trial-positive-in-covid-outpatients.html)
. [Last accessed: March 2022].

16.  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.

17.  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.

18.  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.

19.  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.

20.  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

 

This information is provided by RNS, the news service of the London Stock Exchange. RNS is approved by the Financial Conduct Authority to act as a Primary Information Provider in the United Kingdom. Terms and conditions relating to the use and distribution of this information may apply. For further information, please contact
rns@lseg.com (mailto:rns@lseg.com)
 or visit
www.rns.com (http://www.rns.com/)
.

RNS may use your IP address to confirm compliance with the terms and conditions, to analyse how you engage with the information contained in this communication, and to share such analysis on an anonymised basis with others as part of our commercial services. For further information about how RNS and the London Stock Exchange use the personal data you provide us, please see our
Privacy Policy (https://www.lseg.com/privacy-and-cookie-policy)
.   END  MSCBDLLLLXLXBBF