TIDMAZN
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 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 , 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) - d erived 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 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. 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(TM)(Tixagevimab
Co-Packaged with Cilgavimab). Available at:
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
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 or visit 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.
END
REABKKBDPBKKQCB
(END) Dow Jones Newswires
September 20, 2022 02:00 ET (06:00 GMT)
Astrazeneca (LSE:0A4J)
Historical Stock Chart
From Apr 2024 to May 2024
Astrazeneca (LSE:0A4J)
Historical Stock Chart
From May 2023 to May 2024