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- position results from the Paraphernalia Phase III COVID-19 treatment trial showed AstraZeneca’s AZD7442, a long amusement antibody (LAAB) combination, achieved a statistically significant reduction in severe COVID-19 or death compared to placebo innon-hospitalised cases with mild-to-moderate characteristic COVID-19.

A aggregate of 90 of actors enrolled were from populations at high threat of progression to severe COVID-19, including those withco-morbidities.

The trial met the primary endpoint, with a cure of 600 mg of AZD7442 given by intramuscular (IM) injection reducing the threat of developing severe COVID-19 or death (from any cause) by 50 compared to placebo in rehabilitants who had been characteristic for seven days or lower. The trial recorded 18 events in the AZD7442 arm (18/407) and 37 in the placebo arm (37/415). The LAAB was generally well permitted in the trial.

In a prespecified analysis of actors who entered treatment within five days of symptom onset, AZD7442 reduced the threat 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 fluently administered by IM injection.

Hugh Montgomery, Professor of Intensive Care Medicine at University College London, and Paraphernalia star investigator, said “ With continued cases of serious COVID-19 infections across the globe, there’s a significant need for new curatives like AZD7442 that can be used to cover vulnerable populations from getting COVID-19 and can also help help progression to severe complaint. These positive results show that a accessible intramuscular cure of AZD7442 could play an important part in helping combat this ruinous epidemic.”

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said “ These important results for AZD7442, our long- amusement antibody combination, add to the growing body of substantiation for use of this remedy in both forestallment and treatment of COVID-19. An early intervention with our antibody can give a significant reduction in progression to severe complaint, with uninterrupted protection for further than six months.”

Paraphernalia included 903 actors in a 11 randomisation AZD7442 to placebo. The primary analysis was grounded on 822 actors.

AstraZeneca will be agitating the data with health authorities. On 5 October 2021, the Company blazoned 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 Paraphernalia will be submitted for publication in a peer- reviewed medical journal and presented at a forthcoming medical meeting.

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.

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 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, the human monoclonal antibodies bind to distinct sites on the SARS-CoV-2 spike protein1 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 administration2-4; 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.

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.

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