Astazeneca antibody therapy approved in the United States for pre-exposure prophylaxis.
In a high-risk population, pivotal phase III data of Evusheld demonstrated robust efficacy and long-term protection with a single dose.
My wife, a kidney transplant recipient, was contacted last week by a Kaiser Nephrologist who informed her that a new intramuscular injection called Evusheld by Atrazeneca had been cleared for use in people with compromised immune systems or people taking medications known to suppress the immune system, such as anti-rejection medications used in transplant patients. The nephrologist further explained how recent studies exhibited the Covid-19 vaccinations and booster shots to be 100% ineffective in the prevention of contracting Covid-19 in individuals with compromised immune systems; specifically noting individuals taking immunosuppressive medications often used by transplant recipients, such as Tachrolymus (Prograf) and Mycophenolate (Cellcept).
Evusheld (tixagevimab co-packaged with cilgavimab), a long-acting antibody (LAAB) combination developed by AstraZeneca, has received emergency use authorization (EUA) in the United States for the pre-exposure prophylaxis (prevention) of COVID-19, with the first doses expected to be available soon.
The FDA approved Evusheld for COVID-19 pre-exposure prophylaxis 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 infected with SARS-CoV-2 or have had recent known exposure to someone who is.
"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," said Myron J. Levin, MD, Professor of Pediatrics and Medicine, University of Colorado School of Medicine, US, and principal investigator on the PROVENT trial. I am excited to offer Evusheld to my patients as an easy-to-administered new option that provides long-lasting protection and may help them return to their normal lives."
"We are proud to play a leading role in fighting the COVID-19 pandemic, and with Evusheld, we now have the first antibody therapy approved in the US to prevent COVID-19 symptoms before virus exposure, while also providing long-lasting protection with a single dose," Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said. Evusheld has been shown to neutralize all previous SARs-CoV-2 variants, and we are working quickly to confirm its efficacy against the new Omicron variant. We thank our clinical trial participants, investigators, scientists, government agencies, and AstraZeneca colleagues who all contributed to the development of Evusheld."
"One of the primary questions I keep getting asked by patients is 'When can I hug my grandchildren again?'" said Brian Koffman, MDCM (retired), MS Ed, Co-Founder, Executive Vice President, and Chief Medical Officer of the CLL (Chronic Lymphocytic Leukemia) Society, US. As a physician and person with a weakened immune system, I am encouraged that Evusheld will soon be available to those who cannot rely on vaccination alone to provide the necessary protection."
Evusheld is a combination of two long-acting monoclonal antibodies. It is the only antibody therapy approved in the United States for COVID-19 pre-exposure prophylaxis, as well as the only COVID-19 antibody administered intramuscularly (150mg tixagevimab and 150mg cilgavimab).
Approximately 2% of the global population is thought to be at increased risk of an inadequate response to a COVID-19 vaccine. Around seven million people in the United States are immunocompromised and may benefit from Evusheld for COVID-19 pre-exposure prophylaxis. This includes people undergoing chemotherapy for blood cancers or other cancers, as well as those receiving medications following an organ transplant or taking immunosuppressive drugs for conditions such as multiple sclerosis and rheumatoid arthritis.
Consult your physician to see if Astazeneca's Evusheld intramuscular injection is an effective treatment regiment for you.
SARS-CoV-2 and Evusheld variants
Studies are being conducted to determine the impact of the new Omicron variant (B.1.1.529) on Evusheld.
To date, no Omicron binding site substitutions relevant to Evusheld have been associated with escape from Evusheld neutralisation in preclinical assays. In vitro results show that Evusheld neutralizes other recently emerged SARS-CoV-2 viral variants, such as the Delta and Mu variants.
Evusheld is being developed with federal funds from the Department of Health and Human Services; the Office of the Assistant Secretary for Preparedness and Response; the Biomedical Advanced Research and Development Authority in collaboration with the Department of Defense; and the Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense, under Contract No. W911QY-21-9-0001.
AstraZeneca has agreed to provide the US government with 700,000 Evusheld doses.
The federal government of the United States has stated that it intends to distribute these doses to states and territories at no cost and on a pro rata basis.
AstraZeneca is moving forward with filings for potential emergency use authorization or conditional approval of Evusheld in both COVID-19 prophylaxis and treatment around the world.
NOTE:
This article is not intended to treat or diagnose. Individuals are advised to seek further information about Astazeneca Evusheld as a treatment modal from their attending medical professional staff and acting physician.
Evusheld
Evusheld, formerly known as AZD7442, is a combination of two LAABs derived from convalescent patients' B-cells, tixagevimab (AZD8895) and cilgavimab (AZD1061). Human monoclonal antibodies discovered by Vanderbilt University Medical Center and licensed to AstraZeneca in June 2020 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. When compared to conventional antibodies, the half-life extension more than triples the durability of its action and could provide up to 12 months of protection from COVID-19 after a single administration; data from the Phase III PROVENT trial show protection lasting at least six months. The reduced Fc receptor binding is intended to reduce the risk of antibody-dependent disease enhancement, which occurs when virus-specific antibodies promote, rather than inhibit, infection and/or disease. Evusheld is administered in two separate, consecutive injections of 150mg tixagevimab and 150mg cilgavimab.
AstraZeneca announced in August 2021 that Evusheld demonstrated a statistically significant reduction in the risk of developing symptomatic COVID-19 in the PROVENT trial, with efficacy of 83 percent compared to placebo in a six-month analysis published on November 18, 2021. AstraZeneca will announce positive high-level results from the Evusheld TACKLE Phase III outpatient treatment trial in October 2021. Evusheld is also being investigated as a potential treatment for COVID-19 hospitalized patients as part of the National Institute of Health's ACTIV-3 trial and an additional collaborator hospitalisation treatment trial.
AstraZeneca will pay single-digit royalties on future net sales under the terms of the licensing agreement with Vanderbilt.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global biopharmaceutical company focused on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. AstraZeneca, headquartered in Cambridge, UK, operates in over 100 countries, with millions of patients worldwide benefiting from its innovative medicines. Please visit astrazeneca.com and follow @AstraZeneca on Twitter.
References
1. Oliver, S MD. Data and clinical considerations for additional doses in immunocompromised people. ACIP Meeting July 22, 2021. Available at: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-07/07-COVID-Oliver-508.pdf. [Last accessed: December 2021].
2. AstraZeneca data on file.
3. Taken as percentage of U.S Population: 328.2m (2019).
4. CDC: Lower range: adult pneumococcal vaccine (~25% ), mid range: flu (~48%), upper range: COVID vaccine (~70%).
5. Centers for Disease Control and Prevention. Altered Immunocompetence. General Best Practice Guideline for Immunization: Best Practices Guidance of the Advisory Committee on Immunization Practices. [Online]. Available at: https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/immunocompetence.html. [Last accessed: December 2021].
6. Boyarsky BJ, et al. Immunogenicity of a Single Dose of SARS-CoV-2 Messenger RNA Vaccine in Solid Organ Transplant Recipients. JAMA. 2021; 325 (17):1784-1786.
7. Rabinowich L, et al. Low immunogenicity to SARS-CoV-2 vaccination among liver transplant recipients, Journal of Hepatology (2021). doi: https://doi.org/10.1016/ j.jhep.2021.04.020.
8. Deepak P, et al. Glucocorticoids and B Cell Depleting Agents Substantially Impair Immunogenicity of mRNA Vaccines to SARS-CoV-2. medRxiv [Preprint]. 2021 Apr 9:2021.04.05.21254656. doi: 10.1101/2021.04.05.21254656. PMID: 33851176; PMCID: PMC8043473.
9. Simon D, et al. SARS-CoV-2 vaccination responses in untreated, conventionally treated and anticytokine-treated patients with immune-mediated inflammatory diseases. Ann Rheum Dis. 2021 May 6: annrheumdis-2021-220461. doi: 10.1136/annrheumdis-2021-220461. Epub ahead of print. PMID: 33958324.
10. ACTIV. National Center for Advancing Translational Sciences Open Data Portal. SARS-CoV-2 Variants & Therapeutics, All Variants Reported in vitro Therapeutic Activity. Available at: https://opendata.ncats.nih.gov/variant/activity. [Last accessed: December 2021].
11. Bloom Labs. Available from:
https://twitter.com/jbloom_lab/status/1464005705891868702/photo/1 [Last accessed December 2021].
12. AstraZeneca data on file.
13. Dong J, et al. Genetic and structural basis for recognition of SARS-CoV-2 spike protein by a two-antibody cocktail. bioRxiv. 2021; doi: 10.1101/2021.01.27.428529.
14. Robbie GJ, et al. A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults. Antimicrob Agents Chemother. 2013; 57 (12): 6147-53.
15. 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.
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.
17. AstraZeneca news release. New analyses of two AZD7442 COVID-19 trials in high-risk populations confirm robust efficacy and long-term prevention. Available at: https://www.astrazeneca.com/media-centre/press-releases/2021/new-analyses-of-two-azd7442-covid-19-phase-iii-trials-in-high-risk-populations-confirm-robust-efficacy-and-long-term-prevention.html. [Last accessed: December 2021]
18. van Erp EA, et al. Fc-mediated antibody effector functions during respiratory syncytial virus infection and disease. Front Immunol. 2019; 10: 548.
