New Analyses of Two AZD7442 COVID-19 Phase III Trials in High-Risk Populations Confirm Robust Efficacy and Long-Term Prevention
Six-months follow-up of prevention trial showed 83% reduced risk of symptomatic COVID-19, with no severe disease or deaths with AZD7442
Separate treatment trial showed 88% reduced risk of severe COVID-19 or death when treated within three days of symptom onset
In an analysis of the ongoing PROVENT trial evaluating a median six months of participant follow-up, one 300mg IM dose of AZD7442 reduced the risk of developing symptomatic COVID-19 compared to placebo by 83%.
About 2% of the global population is considered at increased risk of an inadequate response to a COVID-19 vaccine.1 This includes people with blood cancers or other cancers being treated with chemotherapy, patients on dialysis, those taking medications after an organ transplant or who are taking immunosuppressive drugs for conditions including multiple sclerosis and rheumatoid arthritis.2-6
The AZD7442 PROVENT trial is the first Phase III trial prospectively designed to evaluate a monoclonal antibody for pre-exposure prophylaxis of symptomatic COVID-19, with targeted inclusion of high-risk and immunocompromised participants. More than 75% of PROVENT participants at baseline had co-morbidities that put them at high risk for severe COVID-19 if they were to become infected, including people who are immunocompromised and may have a reduced immune response to vaccination.
There were no cases of severe COVID-19 or COVID-19-related deaths in those treated with AZD7442 at either the primary or six-month analyses. In the placebo arm, there were two additional cases of severe COVID-19 at the six-month assessment, for a total of five cases of severe COVID-19 and two COVID-related deaths.
An exploratory analysis of the TACKLE outpatient treatment trial, in patients with mild-to-moderate COVID-19, showed that one 600mg IM dose of AZD7442 reduced the risk of developing severe COVID-19 or death (from any cause) by 88% compared to placebo in patients who had been symptomatic for three days or less at the time of treatment.
A total of 90% of participants enrolled in TACKLE were from populations at high risk of progression to severe COVID-19 if they became infected, including those with co-morbidities.
In both PROVENT and TACKLE, AZD7442 was generally well tolerated. No new safety issues were identified in the six-month analysis of PROVENT.
Full results from PROVENT and TACKLE will be submitted for publication in a peer-reviewed medical journal and presented at a forthcoming medical meeting.
PROVENT is a Phase III, randomized, double-blind, placebo-controlled, multi-center trial assessing the safety and efficacy of a single IM 300mg dose of AZD7442 compared to placebo for the prevention of COVID-19 in participants who did not have who did not have SARS-CoV-2 infection at baseline. The trial was conducted in 87 sites in the US,
The primary analysis reported on
Participants were adults 18 years-old and over who would benefit from prevention with the LAAB, defined as having increased risk for inadequate response to active immunization (predicted poor responders to vaccines or intolerant of vaccine) or having increased risk for SARS-CoV-2 infection, including those whose locations or circumstances put them at appreciable risk of exposure to the SARS-CoV-2 virus. Participants at the time of screening were unvaccinated and had a negative point-of-care SARS-CoV-2 serology test.
Approximately 43% of participants were 60 years and over. In addition, more than 75% had baseline co-morbidities and other characteristics that are associated with an increased risk for severe COVID-19 should they become infected, including those with immunosuppressive disease or taking immunosuppressive medications, diabetes, severe obesity or cardiac disease, chronic obstructive pulmonary disease, chronic kidney and chronic liver disease.
TACKLE is a Phase III, randomized, double-blind, placebo-controlled, multi-center trial assessing the safety and efficacy of a single 600mg IM dose of AZD7442 compared to placebo for the outpatient treatment of COVID-19. 903 participants were randomized (1:1) to receive either AZD7442 (n = 452) or saline placebo (n = 451), administered in two separate, sequential IM injections. The primary analysis was reported on
Participants were adults 18 years-old and over who were non-hospitalized 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.
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
AZD7442 is also being studied as a potential treatment for hospitalized 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.13 Additional in vitro findings demonstrate AZD7442 neutralizes recent emergent SARS-CoV-2 viral variants, including the Delta and Mu variants.14
Under the terms of the licensing agreement with Vanderbilt,
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- 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.
- 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.
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