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Evusheld authorized for emergency use in US for pre-exposure prevention of COVID

Sameh El Fangary – AstraZeneca CP GCC Cluster

AstraZeneca’s Evusheld (tixagevimab co-packaged with cilgavimab), a long-acting antibody (LAAB) combination, has received emergency use authorization (EUA) in the US for the pre-exposure prophylaxis (prevention) of COVID-19, with first doses expected to become available very soon.

The Food and Drug Administration (FDA) granted the EUA for Evusheld for pre-exposure prophylaxis of COVID-19 in adults and adolescents (aged 12 and older who weigh 40 kg or more) with moderate to severe immune compromise due to a medical condition or immunosuppressive medications and who may not mount an adequate immune response to COVID-19 vaccination, as well as those individuals for whom COVID-19 vaccination is not recommended. Recipients should not be currently infected with or had recent known exposure to a person infected with SARS-CoV-2.

Myron J Levin, MD, Professor of Pediatrics and Medicine, University of Colorado School of Medicine, US, and principal investigator on the PROVENT trial, said: “Millions of people in the US and around the world remain at serious risk for COVID-19 because their immune systems do not generate a sufficient immune response, even after receiving all recommended doses of vaccine. I am excited to offer my patients Evusheld as an easily-administered new option that provides long-lasting protection that could help them return to their everyday lives.”

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “We are proud to play a leading role in fighting the COVID-19 pandemic and, with Evusheld, we now have the first antibody therapy authorized in the US to prevent COVID-19 symptoms before virus exposure, while also providing long lasting protection with a single dose. Evusheld neutralizes all previous SARs-CoV-2 variants to date, and we are working quickly to establish its efficacy against the new Omicron variant. We thank our clinical trial participants, the investigators, scientists, and government agencies and our colleagues at AstraZeneca who have all contributed to the development of Evusheld.”

Brian Koffman, MDCM (retired), MS Ed, Co-Founder, Executive Vice President and Chief Medical Officer of the CLL (Chronic Lymphocytic Leukemia) Society, US, said: “One of the primary questions I keep getting asked by patients is ‘When can I hug my grandchildren again?’ As a physician and person with a weakened immune system, l am filled with hope now that Evusheld will soon be available to those who can’t count on vaccination alone to provide the protection they need.”

Evusheld is a combination of two long-acting monoclonal antibodies and is the only antibody therapy authorized in the US for COVID-19 pre-exposure prophylaxis and the only COVID-19 antibody delivered as an intramuscular dose (150mg tixagevimab and 150mg cilgavimab).

About 2 percent 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, and those taking medications after an organ transplant or who are taking immunosuppressive drugs for conditions including multiple sclerosis and rheumatoid arthritis.

The primary data supporting the Evusheld EUA are from the ongoing PROVENT Phase III pre-exposure prevention trial, which showed a statistically significant reduction (77 percent at primary analysis, 83 percent at median six-month analysis) in the risk of developing symptomatic COVID-19 compared to placebo, with protection from the virus continuing for at least six months. More follow-up is needed to establish the full duration of protection provided by Evusheld. Data from the Phase III STORM CHASER post-exposure trial and the Evusheld Phase I trial also supported the EUA. Evusheld was well-tolerated in the trials.

Evusheld and SARS-CoV-2 variants
Studies are underway to provide information on the impact of the new Omicron variant (B.1.1.529) on Evusheld. Of the Omicron binding site substitutions relevant to Evusheld that have been tested to date in preclinical assays, none have been associated with escape from Evusheld neutralization. In vitro findings demonstrate Evusheld neutralizes other recent emergent SARS-CoV-2 viral variants, including the Delta and Mu variants.

Evusheld 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.

Sameh El Fangary, Country President, GCC & Pakistan, AstraZeneca, “The US Food and Drug Administration’s EUA of Evusheld (formerly AZD7442) for the prevention of COVID-19 is an important milestone globally. We welcome this news and the opportunity it provides to support the unmet needs of vulnerable patients.”

AstraZeneca has agreed to supply the US government with 700,000 doses of Evusheld. These initial doses of Evusheld will be available at no cost to eligible patients as part of a government-funded program. The US government will be working with states to provide access to eligible people. AstraZeneca is progressing with filings around the globe for potential emergency use authorization or conditional approval of Evusheld in both COVID-19 prophylaxis and treatment.

Evusheld, formerly known as 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 protein 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 administration; data from the Phase III PROVENT trial show protection lasting at least six 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. Evusheld is delivered as an IM dose of 150mg tixagevimab and 150mg cilgavimab administered in two separate, consecutive injections.

In Aug 2021, AstraZeneca announced that Evusheld demonstrated a statistically significant reduction in the risk of developing symptomatic COVID-19 in the PROVENT trial; efficacy was 83 percent compared to placebo in a six-month analysis announced on Nov 18, 2021. In Oct 2021, AstraZeneca announced positive high-level results from the Evusheld TACKLE Phase III outpatient treatment trial.

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

NOTE: Evusheld has received emergency use authorization in Bahrain. Please note that Evusheld is not currently approved for use in the UAE, KSA, Kuwait, Qatar or Oman.

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