US authorizes AstraZeneca's Evusheld for pre-exposure prevention of COVID-19

New Delhi [India], December 9 : AstraZeneca's Evusheld (Tixagevimab co-packaged with Cilgavimab), a long-acting antibody (LAAB) combination, has received emergency use authorisation (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 40kg or more) with moderate to severe immune-compromised 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 Paediatrics 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 authorised in the US to prevent COVID-19 symptoms before virus exposure, while also providing long-lasting protection with a single dose."
"Evusheld neutralises 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," said Pangalos.
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 authorised 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 per cent of the global population is considered at increased risk of an inadequate response to a COVID-19 vaccine 1,2 In India, this percentage could be a bit higher given the problem of underdiagnosis and ignorance. This includes people with blood cancers or other cancers being treated with chemotherapy, and those taking medications after an organ transplant or who are taking immunosuppressive drugs for conditions including multiple sclerosis and rheumatoid arthritis.5-9
Gagandeep Singh Bedi, Managing Director AstraZeneca India Pharma Limited added, "The U.S. Food and Drug Administration's EUA approval of 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 high risk and immune-compromised patients and we have already initiated engagements with the relevant health authorities in India to provide them with the latest evidence. Recent data from the Phase III PROVENT trial showed a robust efficacy profile and AZD7442 has so far demonstrated protection of up to six months against COVID-19 in this population," said Bedi.
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 per cent at primary analysis, 83 per cent 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.
Studies are underway to provide information on the impact of the new Omicron variant (B.1.1.529) on Evusheld.10,11 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 neutralisation.10,11. In vitro findings demonstrate Evusheld neutralises other recent emergent SARS-CoV-2 viral variants, including the Delta and Mu variants.10
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.
AstraZeneca has agreed to supply the US government with 700,000 doses of Evusheld. The U.S. government has indicated that it plans to distribute these doses to states and territories at no cost and on a pro-rata basis.
AstraZeneca is progressing with filings around the globe for potential emergency use authorisation or conditional approval of Evusheld in both COVID-19 prophylaxis and treatment.
In India, the company intends to submit its application after emergency use authorization by USFDA with the hope that the addition of this monoclonal antibody cocktail will provide adequate ammunition in the fight against COVID-19 disease, especially for high risk vulnerable and immunocompromised patients.