TIDMAZN
RNS Number : 5779O
AstraZeneca PLC
11 October 2021
11 October 2021 07:00 BST
AZD7442 reduced risk of developing severe COVID-19 or death
in TACKLE Phase III outpatient treatment trial
Trial met primary endpoint
AZD7442 is the only long-acting antibody combination shown
to both prevent and treat COVID-19
Positive high-level results from the TACKLE Phase III COVID-19
treatment trial showed AstraZeneca's AZD7442, a long acting
antibody (LAAB) combination, achieved a statistically significant
reduction in severe COVID-19 or death compared to placebo in
non-hospitalised patients with mild-to-moderate symptomatic
COVID-19.
A total of 90% of participants enrolled were from populations at
high risk of progression to severe COVID-19, including those with
co-morbidities.
The trial met the primary endpoint, with a dose of 600mg of
AZD7442 given by intramuscular (IM) injection reducing the risk of
developing severe COVID-19 or death (from any cause) by 50%
compared to placebo in outpatients who had been symptomatic for
seven days or less. The trial recorded 18 events in the AZD7442 arm
(18/407) and 37 in the placebo arm (37/415). The LAAB was generally
well tolerated in the trial.
In a prespecified analysis of participants who received
treatment within five days of symptom onset, AZD7442 reduced the
risk of developing severe COVID-19 or death (from any cause) by 67%
compared to placebo, with nine events in the AZD7442 arm (9/253)
and 27 in the placebo arm (27/251).
AZD7442 is the first LAAB with Phase III data to demonstrate
benefit in both prophylaxis and treatment of COVID-19 and is easily
administered by IM injection.
Hugh Montgomery, Professor of Intensive Care Medicine at
University College London, and TACKLE principal investigator, said:
"With continued cases of serious COVID-19 infections across the
globe, there is a significant need for new therapies like AZD7442
that can be used to protect vulnerable populations from getting
COVID-19 and can also help prevent progression to severe disease.
These positive results show that a convenient intramuscular dose of
AZD7442 could play an important role in helping combat this
devastating pandemic."
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, AstraZeneca, said: "These important results for AZD7442,
our long-acting antibody combination, add to the growing body of
evidence for use of this therapy in both prevention and treatment
of COVID-19. An early intervention with our antibody can give a
significant reduction in progression to severe disease, with
continued protection for more than six months."
TACKLE included 903 participants in a 1:1 randomisation AZD7442
to placebo. The primary analysis was based on 822 participants.
AstraZeneca will be discussing the data with health authorities.
On 5 October 2021, the Company announced that it had submitted a
request to the US Food and Drug Administration for Emergency Use
Authorisation for AZD7442 for prophylaxis of COVID-19.
Full results from TACKLE will be submitted for publication in a
peer-reviewed medical journal and presented at a forthcoming
medical meeting.
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 AZD7442 compared to placebo
for the outpatient treatment of COVID-19. The trial was conducted
in 96 sites in Brazil, Czech Republic, Germany, Hungary, Italy,
Japan, Mexico, Poland, Russian Federation, Spain, Ukraine, UK and
US . 903 participants were randomised (1:1) to receive either
AZD7442 (n = 452) or saline placebo (n = 451), administered in two
separate, sequential IM injections.
Participants were adults 18 years-old and over who were
non-hospitalised with mild-to-moderate COVID-19 and 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 one.
The primary efficacy endpoint was the composite of either severe
COVID-19 or death from any cause through day 29. Subjects will
continue to be followed for 15 months.
Approximately 13% of participants were 65 years and over. In
addition, 90% had baseline co-morbidities and other characteristics
that put them at high risk of progression to severe COVID-19,
including cancer, diabetes, obesity, chronic lung disease or
asthma, cardiovascular disease or immunosuppression. Approximately
62% were White/Caucasian, 4% Black/African-American, 6% Asian and
24% American Indian or Alaskan Native. Approximately 52% of
participants were Hispanic/Latino.
AZD7442
AZD7442 is a combination of two LAABs - tixagevimab (AZD8895)
and cilgavimab (AZD1061) - d erived 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 , the human monoclonal antibodies bind to distinct sites
on the SARS-CoV-2 spike protein(1) 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(2-4) ; data from the Phase I
trial show high neutralising antibody titres for at least nine
months.(5) 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.(6)
In August 2021, AstraZeneca announced AZD7442 demonstrated a
statistically significant reduction in the risk of developing
symptomatic COVID-19 in the PROVENT Phase III pre-exposure
prevention trial.
AZD7442 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 and in an additional collaborator
hospitalisation treatment trial.
AZD7442 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.
In preclinical experiments, data show the LAABs were able to
block the binding of the SARS-CoV-2 virus to host cells and protect
against infection in cell and animal models of disease.(7)
Additional in vitro findings demonstrate AZD7442 neutralises recent
emergent SARS-CoV-2 viral variants, including the Delta and Mu
variants.(8)
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. 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.
2. 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.
3. 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.
4. 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.
5. Loo Y-M, et al. AZD7442 demonstrates prophylactic and
therapeutic efficacy in non-human primates and extended half-life
in humans. medRxiv. Cold Spring Harbor Laboratory Press; 2021
[preprint] Available from:
https://www.medrxiv.org/content/10.1101/2021.08.30.21262666v1 .
6. van Erp EA, et al. Fc-mediated antibody effector functions
during respiratory syncytial virus infection and disease. Front
Immunol. 2019; 10: 548.
7. Zost SJ, et al. Potently neutralizing and protective human
antibodies against SARS-CoV 2. Nature. 2020; 584: 443-449.
8. ACTIV. National Center for Advancing Translational Sciences
OpenData Portal. SARS-CoV-2 Variants & Therapeutics, All
Variants Reported in vitro Therapeutic Activity. Available at:
https://opendata.ncats.nih.gov/variant/activity [Last accessed:
September 2021].
Adrian Kemp
Company Secretary
AstraZeneca PLC
, 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
MSCFLFLAIALILIL
(END) Dow Jones Newswires
October 11, 2021 02:00 ET (06:00 GMT)
Astrazeneca (LSE:AZN)
Historical Stock Chart
From Aug 2024 to Sep 2024
Astrazeneca (LSE:AZN)
Historical Stock Chart
From Sep 2023 to Sep 2024