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

AstraZenecaAnnouncement

20/09/2022 07:00

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RNS Number : 9500Z  AstraZeneca PLC  20 September 2022

20 September 2022 07:00 GMT

 

Evusheld long-acting antibody combination approved in the EU

for the treatment of COVID-19

 

Evusheld significantly reduced risk of severe COVID-19 or death

in TACKLE Phase III treatment trial

 

AstraZeneca's Evusheld (tixagevimab and cilgavimab, formerly AZD7442), a
long-acting antibody combination, has been approved 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 approval by the European Commission was based 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: "Many people,
including those who are immunocompromised, older adults and those with
underlying health conditions, are at high risk of severe disease,
hospitalisation and death if they become infected. Evusheld, delivered in a
convenient intramuscular formulation, is now a much-needed new COVID-19
treatment option for these vulnerable populations."

 

Iskra Reic, Executive Vice President, Vaccines and Immune Therapies,
AstraZeneca, said: "COVID-19 remains an ongoing health concern for millions of
Europeans and around the world, especially for those who may not be
well-protected against the virus from vaccination. With this approval,
Evusheld is now the only long-acting antibody combination available for both
prevention and treatment of COVID-19 in Europe, allowing us to protect even
more people from this devastating disease."

 

The recommended dose of Evusheld for treatment in Europe is 300mg of
tixagevimab and 300mg of cilgavimab, administered as two separate, sequential
IM injections.

 

Evusheld has 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
(https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2022/evusheld-approved-in-the-eu-for-covid-19.html)
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.

 

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 TACKLE, published in The Lancet Respiratory Medicine
(https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(22)00180-1/fulltext)
, 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 protein(7) 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 (https://www.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.   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
(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

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