COVID-19 Antibody (AZD7442) Description
The COVID-19 Antibody (AZD7442) has been engineered with AstraZeneca’s proprietary half-life extension technology to increase the therapy's durability for six to 12 months following a single administration.
AZD7442 is the first antibody combination (non-vaccine) modified to potentially provide long-lasting protection that has demonstrated the prevention of COVID-19 in a clinical trial. It is a combination of tixagevimab (AZD8895) and cilgavimab (AZD1061).
AstraZeneca's COVID-19 Long-Acting Antibody (LAABs) mimic natural antibodies and have the potential to treat and prevent disease progression in patients already infected with the virus, as well as to be given as a preventative intervention before exposure to the virus.
Discovered by Vanderbilt University Medical Center and licensed to AstraZeneca in June 2020, the LAABs were optimized by AstraZeneca with half-life extension and reduced Fc receptor binding. The half-life extended LAABs should afford six to 12 months of protection from COVID-19. 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.
This LAAB combination (AZD8895 + AZD1061) could complement vaccines as a prophylactic agent, e.g., for people for whom a vaccine may not be appropriate or provide added protection for high-risk populations. It could also be used to treat people who have been infected.
AZD7442 contains infection-fighting proteins called monoclonal antibodies that work to neutralize the virus, thus preventing COVID-19. Each dose is given once as two intramuscular shots in each gluteal region within eight days of exposure.
Mene Pangalos, EVP, BioPharmaceuticals R&D, said in a press statement issued on August 20, 2021, “We need additional approaches for individuals who are not adequately protected by COVID-19 vaccines. We are very encouraged by these efficacy and safety data in high-risk people, showing our long-acting antibody combination has the potential to protect from symptomatic and severe disease, alongside vaccines. We look forward to sharing further data from the AZD7442 Phase III clinical trial program later this year.”
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. Based in Cambridge, UK, AstraZeneca (LSE/STO/Nasdaq: AZN) operates in over 100 countries, and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com for additional information.
COVID-19 Antibody (AZD7442) History
In a Nature publication in July 2020, LAABs were shown in pre-clinical experiments to block the binding of the SARS-CoV-2 virus to host cells and protect against infection in cell and animal models of disease.
On December 25, 2020, Dr. Houlihan of UCL Infection & Immunity said: “We know that this antibody combination can neutralize the virus, so we hope to find that giving this treatment via injection can lead to immediate protection against the development of Covid-19 in people who have been exposed – when it would be too late to offer a vaccine.”
On February 3, 2021, AstraZeneca stated 'While vaccines train the immune system to fight a future infection, monoclonal antibodies mimic naturally developed antibodies to neutralize SARS-CoV-2 infection immediately. The mutations in the emerging variants of SARS-CoV-2 may induce some escape from these therapeutic interventions. However, when two complementary monoclonal antibodies are combined into one therapeutic intervention, the risk of the combination losing efficacy is considerably diminished as the virus would have to mutate in multiple distinct locations to escape both antibodies' actions. As for the vaccines, continued surveillance of SARS-CoV-2 is the best approach to ensure their success.'
The US Military confirmed on February 23, 2021, it was participating in a new COVID-19 antibody combination prevention trial. STORM CHASER also aims to see if individuals who receive the AZD7442 injection after SARS-CoV-2 exposure experience less severe symptoms of COVID-19.
Dr. Myron J. Levin, Professor of Pediatrics and Medicine, University of Colorado School of Medicine, US, and principal investigator on the trial, said in a press release issued on August 20, 2021, “The PROVENT data show that one dose of AZD7442, delivered in a convenient intramuscular form, can quickly and effectively prevent symptomatic COVID-19. With these exciting results, AZD7442 could be an important tool in our arsenal to help people who may need more than a vaccine to return to their normal lives.”
AstraZeneca is a global, science-led biopharmaceutical company.
COVID-19 Antibody (AZD7442) Indication
AZD7422 (AZD8895 + AZD1061) is indicated to prevent infection from the SARS-CoV-2 virus and treat patients who have become infected by the SARS-Cov-2 coronavirus and developed COVID-19 disease. Participants randomized to AZD7442 will be administered dose 1 in Cohort 1a (IM) and Cohort 1b (IV). Participants in Cohort 2 and 3 will receive AZD7442 (IV) doses 2 and 3, respectively.
COVID-19 Antibody (AZD7442) Side Effects
The LAAB was well tolerated, and preliminary analyses show adverse events were balanced between the placebo and AZD7442 groups.
COVID-19 Antibody (AZD7442) News
September 7, 2021 - Reuters reported Japan has selected the antibody treatment AZD7442 to receive subsidies for clinical trials.
August 20, 2021 - AstraZeneca announced the AZD7442 PROVENT Phase III prophylaxis trial met the primary endpoint in preventing COVID-19. AZD7442 achieved a statistically significant reduction in the incidence of symptomatic COVID-19, the trial's primary endpoint.
June 15, 2021 - AstraZeneca announced results from the STORM CHASER trial assessing the safety and efficacy of AZD7442. Compared to placebo, the trial did not meet the primary endpoint of post-exposure prevention of symptomatic COVID-19 with AZD7442. Trial participants were unvaccinated adults 18 years and over with confirmed exposure to a person with a case of the SARS-CoV-2 virus within the past eight days. In the overall trial population, AZD7442 reduced the risk of developing symptomatic COVID-19 by 33% (95% confidence interval (CI): -26, 65) than placebo, which was not statistically significant.
February 8, 2021 - The U.S. NIH published: Clinical trial in hospitalized COVID-19 patients evaluates long-acting antibody therapy.
February 3, 2021 - Arizona-based Matrix Medical Network announced a collaboration with global biopharmaceutical company AstraZeneca to accelerate a clinical trial in the US for AZD7442, AstraZeneca’s long-acting monoclonal antibody combination for the potential prevention of COVID-19. Matrix Clinical Solutions will meet eligible volunteers who live and work with a fleet of Mobile Health Clinics and skilled clinicians, focusing on populations more impacted by COVID-19. Matrix supports the Phase III clinical trial called STORM CHASER, which will assess the safety and efficacy of AZD7442 for post-exposure prophylaxis in approximately 1,125 participants in the US UK. Participants in this trial will include adults over 18 years of age following exposure to SARS-COV-2 and are therefore at appreciable risk of developing COVID-19. The trial will include people living or working at long-term care facilities and industrial and military settings.
December 30, 2020 - Panthera’s clinical trial sites in Preston, North Manchester, and North London began dosing volunteers in the Phase III PROVENT trial, which will evaluate AstraZeneca’s long-acting antibody combination, AZD7442, for the potential prevention of COVID-19.
December 25, 2020 - Researchers in the STORM CHASER study led by UCLH virologist Dr. Catherine Houlihan has recruited the first participant in the world to the study. They believe the antibody or LAAB, known as AZD7442 and developed by AstraZeneca, may offer immediate and long-term protection to people who have been recently exposed to the SARS-CoV-2 virus to prevent them from developing Covid-19.
October 9, 2020 - Two trials of AZD7442 will enroll over 6,000 adults to prevent COVID-19, with additional trials enrolling ~4,000 adults for the treatment of SARS-CoV-2 infections.
July 15, 2020 - Study published by Nature: Potently neutralize and protect human antibodies against SARS-CoV-2. In two mouse models of SARS-CoV-2 infection, passive transfer of COV2-2196, COV2-2130, or a combination of both of these antibodies protected mice from weight loss. Furthermore, it reduced the viral burden and levels of inflammation in the lungs. In addition, passive transfer of either of two of the most potent ACE2-blocking monoclonal antibodies (COV2-2196 or COV2-2381) as monotherapy protected rhesus macaques from SARS-CoV-2 infection. These results identify protective epitopes on the SRBD and provide a structure-based framework for rational vaccine design and the selection of robust immunotherapeutic agents.
April 8, 2020 - The Chinese Academy of Sciences and Vanderbilt University Medical Center provides AstraZeneca with genetic sequences for antibodies discovered against SARS-CoV-2 for further in silico and in vitro assessment.
COVID-19 Antibody (AZD7442) Clinical Trials
ACTIV-3 is part of the NIH Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership to develop a coordinated research strategy for prioritizing and accelerating the development of the most promising treatments and vaccines. The ACTIV-3 master trial is designed to conduct multiple different trials of experimental therapeutics simultaneously.
Clinical Trial NCT04507256: AZD7442 is a Potential Combination Therapy for the Prevention and Treatment of COVID-19. In this first-in-human dose-escalation study, AZD7442 (AZD8895 + AZD1061) will be evaluated for safety, tolerability, pharmacokinetics generation of anti-drug antibodies (ADAs). The study is intended to enable future studies of AZD7442's efficacy in preventing and treating COVID-19. The study will comprise of: A Screening Period of up to 27 days (Day -28 through Day -2); A Treatment Period during which participants will be resident at the Clinical Unit from Day -1, 1 day before Investigational Medicinal Product (IMP) administration (on Day 1) until at least 24 hours after IMP administration, will be discharged on Day 2 after all safety evaluations have been completed, and a Follow-up Period lasting 360 days (through to Day 361) after the IMP dose.
Clinical Trial NCT04625725 Phase III Double-blind, Placebo-controlled Study of AZD7442 for Pre-exposure Prophylaxis of COVID-19 in Adult. (PROVENT). The PROVENT study will assess the safety and efficacy of a single dose of AZD7442(× 2 IM injections) compared to a placebo to prevent COVID-19.
This Phase III study will assess whether AZD7442 (a combination of 2 mAbs) can safely treat outpatient adults with COVID-19 and prevent either severe COVID-19 or death. Last Update Posted: July 2, 2021.