REG - AstraZeneca PLC - Evusheld US FDA EUA

AstraZenecaAnnouncement

09/12/2021 07:00

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RNS Number : 0533V  AstraZeneca PLC  09 December 2021

 

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
(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(13) 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
(https://www.astrazeneca.com/media-centre/press-releases/2021/azd7442-prophylaxis-trial-met-primary-endpoint.html)
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
(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)
 on 18 November 2021. In October 2021, AstraZeneca announced
(https://www.astrazeneca.com/media-centre/press-releases/2021/azd7442-phiii-trial-positive-in-covid-outpatients.html)
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 (https://clinicaltrials.gov/ct2/show/NCT04501978) 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
(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.   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
(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
(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
(https://opendata.ncats.nih.gov/variant/activity) . [Last accessed: December
2021].

11.  Bloom Labs. Available from:

https://twitter.com/jbloom_lab/status/1464005705891868702/photo/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
(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

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