Only antibody therapy authorized in US for pre-exposure prophylaxis Pivotal phase III data showed robust efficacy and long-term protection with one dose in high-risk population
AstraZeneca’s long-acting antibody combination (tixagevimab co-packaged with cilgavimab called AZD7442), has received emergency use authorization (EUA) in the US for 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 AstraZeneca’s long-acting antibody combination 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 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 AstraZeneca’s long-acting antibody combination 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 AstraZeneca’s long-acting antibody combination, 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. AstraZeneca’s long-acting antibody combination 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 AstraZeneca’s long-acting antibody combination.”
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 AstraZeneca’s long-acting antibody combination will soon be available to those who can’t count on vaccination alone to provide the protection they need.”
Lotis Ramin, Country President of AstraZeneca Philippines said, “The U.S. Food and Drug Administration’s EUA of Astrazeneca AstraZeneca’s long-acting antibody combination for the prevention of COVID-19 is an important milestone globally. We are proud of this development and the opportunity it brings to support the unmet needs of vulnerable patients. There are a number of patients with comorbidities who might have weakened immune system and at greater risk for severe COVID19 infection in the Philippines. We have already initiated engagements with the relevant health authorities to provide them with the latest evidence. Recent data from the Phase III PROVENT trial showed a robust efficacy profile and AstraZeneca’s long-acting antibody (LAAB) combination has so far demonstrated protection of up to six months against COVID-19 in high risk and immune-compromised patients.”
AstraZeneca’s long-acting antibody 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% of the global population is considered at increased risk of an inadequate response to a COVID-19 vaccine.1,2 About seven million people in the US are immunocompromised and may benefit from AstraZeneca’s long-acting antibody combination for pre-exposure prophylaxis of COVID-19.1,3,4 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
The primary data supporting the AstraZeneca’s long-acting antibody combination EUA are from the ongoing PROVENT Phase III pre-exposure prevention trial, which showed a statistically significant reduction (77% at primary analysis, 83% 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 AstraZeneca’s long-acting antibody combination. Data from the Phase III STORM CHASER post-exposure trial and the AstraZeneca’s long-acting antibody combination Phase I trial also supported the EUA. AstraZeneca’s long-acting antibody combination was well-tolerated in the trials.
AstraZeneca’s long-acting antibody combination and SARS-CoV-2 variants
Studies are underway to provide information on the impact of the new Omicron variant (B.1.1.529) on AstraZeneca’s long-acting antibody combination.10,11 Of the Omicron binding site substitutions relevant to AstraZeneca’s long-acting antibody combination that have been tested to date in preclinical assays, none have been associated with escape from AstraZeneca’s long-acting antibody combination neutralisation.10,11 In vitro findings demonstrate AstraZeneca’s long-acting antibody combination neutralises other recent emergent SARS-CoV-2 viral variants, including the Delta and Mu variants.10
AstraZeneca’s long-acting antibody combination 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 AstraZeneca’s long-acting antibody combination. 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 AstraZeneca’s long-acting antibody combination in both COVID-19 prophylaxis and treatment.
AZD7442 is not yet approved for use in the Philippines.
AstraZeneca’s long-acting antibody combination
AstraZeneca’s long-acting antibody combination, 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 protein13 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 administration;14-16 data from the Phase III PROVENT trial show protection lasting at least six months.17 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.18 AstraZeneca’s long-acting antibody combination is delivered as an IM dose of 150mg tixagevimab and 150mg cilgavimab administered in two separate, consecutive injections.
In August 2021, AstraZeneca announced that AstraZeneca’s long-acting antibody combination demonstrated a statistically significant reduction in the risk of developing symptomatic COVID-19 in the PROVENT trial; efficacy was 83% compared to placebo in a six-month analysis announced on 18 November 2021. In October 2021, AstraZeneca announced positive high-level results from the AstraZeneca’s long-acting antibody combination TACKLE Phase III outpatient treatment trial. AstraZeneca’s long-acting antibody combination 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.
Under the terms of the licensing agreement with Vanderbilt, AstraZeneca will pay single-digit royalties on future net sales.
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. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.