Therapy Areas: Inflammatory Diseases
New Analyses of Two AZD7442 COVID-19 Phase III Trials in High-Risk Populations Confirm Robust Efficacy and Long-Term Prevention
19 November 2021 - - New data from the AZD7442 COVID-19 PROVENT prevention and TACKLE outpatient treatment Phase III trials both showed robust efficacy from a one-time intramuscular dose of the long-acting antibody combination, UK-based pharmaceutical and biotechnology company AstraZeneca (NASDAQ: AZN) said.

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.

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.

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.

On October 5, 2021, the company announced that it had submitted a request to the US Food and Drug Administration for Emergency Use Authorization for AZD7442 for prophylaxis of COVID-19.

AstraZeneca has agreed to supply the US government with 700,000 doses of AZD7442 if granted an Emergency Use Authorization by the FDA and has agreements to supply to other countries.
Notes

AstraZeneca is progressing with filings around the globe for potential emergency use authorization or conditional approval of AZD7442 in both prophylaxis and treatment.

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 protein7 and were optimized 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 administration8-10; data from the Phase III PROVENT trial show protection lasting at least six months, with the Phase I trial showing high neutralizing antibody titers for at least nine months.

The reduced Fc receptor binding aims to minimize the risk of antibody-dependent enhancement of disease - a phenomenon in which virus-specific antibodies promote, rather than inhibit, infection and/or disease.

AZD7442 is also being studied as a potential treatment for hospitalized COVID-19 patients as part of the National Institute of Health's ACTIV-3 trial and in an additional collaborator hospitalization 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.13 Additional in vitro findings demonstrate AZD7442 neutralizes recent emergent SARS-CoV-2 viral variants, including the Delta and Mu variants.

Under the terms of the licensing agreement with Vanderbilt, AstraZeneca will pay single-digit royalties on future net sales.
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