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
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.
TACKLE included 903 participants in a 1:1 randomisation AZD7442 to placebo. The primary analysis was based on 822 participants.
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
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/
AZD7442
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
In
AZD7442 is also being studied as a potential treatment for hospitalised COVID-19 patients as part of the
AZD7442 is being developed with support from the
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,
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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.
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.
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