REG - AstraZeneca PLC - Evusheld Positive EU CHMP Opinion

AstraZenecaAnnouncement

24/03/2022 18:00

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RNS Number : 9754F  AstraZeneca PLC  24 March 2022

24 March 2022 18:00 GMT

 

Evusheld long-acting antibody combination recommended for approval

in the EU for the pre-exposure prophylaxis (prevention) of COVID-19

 

Recommendation based on Phase III PROVENT trial showing

a significant reduction in the risk of developing symptomatic COVID-19,

with protection lasting at least six months

 

AstraZeneca's Evusheld (tixagevimab co-packaged with cilgavimab), a
long-acting antibody combination, has been recommended for 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.

 

People not adequately protected by a COVID-19 vaccine may particularly benefit
from pre-exposure prophylaxis with Evusheld. This includes about three million
people in the EU who are immunocompromised or being treated with
immunosuppressive medicines.(1)

( )

The Committee for Medicinal Products for Human Use (CHMP) of the European
Medicines Agency based its positive opinion on a review of Evusheld data,
including results 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 continuing for at least
six months.(2-4) Evusheld was generally well-tolerated in the trial.(2-4)

 

Hugh Montgomery, Professor of Intensive Care Medicine at University College
London, UK and Evusheld investigator said: "Despite the success of
vaccinations, we still need additional measures to prevent the spread of
COVID-19 infections in Europe, where the number of cases of the highly
transmissible BA.2 subvariant is rapidly increasing and where public health
safety measures have been relaxed in many countries. This broad recommendation
for Evusheld will allow health authorities in the EU to identify priority,
high-risk populations needing additional protection such as people with
cancer, transplant patients, or anyone taking immunosuppressive medicines, as
well as those at increased risk of exposure."

 

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D,
AstraZeneca, said: "Today's positive CHMP recommendation represents a
significant step forward in our ongoing efforts to introduce additional,
important preventative measures for people in Europe at higher risk of
developing COVID-19. Evusheld has the potential to provide long-lasting
protection to vulnerable populations such as the immunocompromised who can't
mount an adequate response to a COVID-19 vaccine, and we'll continue to work
with governments in Europe to make Evusheld available as quickly as possible."

 

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.(5-7) 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 nearly 60% of COVID-19 infections in Europe.(7,8)
 This study also showed Evusheld reduced viral burden and limited
inflammation in the lungs (in vivo) across all Omicron variants.(7)

 

Evusheld is authorised for emergency use for pre-exposure prophylaxis of
COVID-19 in the US and in six countries in Europe. Evusheld has also been
granted conditional marketing authorisation by the Medicines and Healthcare
products Regulatory Agency (MHRA) in Great Britain for pre-exposure
prophylaxis of COVID-19.

 

AstraZeneca anticipates that the European Commission will shortly complete its
review of the CHMP positive opinion to determine whether to grant marketing
authorisation.

 

Evusheld is the only long-acting antibody combination with positive Phase III
data in the prevention and treatment of COVID-19.(3,9) 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(10) 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;(11-13) data from the PROVENT Phase III trial show protection
lasting at least six months.(14) 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.(15)

 

Evusheld received Emergency Use Authorisation (EUA) in the US in December 2021
for the pre-exposure prophylaxis (prevention) 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. Evusheld is also authorised for use and being
supplied in several other countries around the world.

 

The primary data supporting the Evusheld EUA 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 (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. 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 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://www.astrazeneca.com/media-centre/press-releases/2021/twitter.com/AstraZeneca)
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.   AstraZeneca Data on File.

2.   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].

3.   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].

4.   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]

5.   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.

6.   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.

7.   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].

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

9.   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].

10.  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.

11.  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.

12.  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.

13.  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.

14.  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

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