Evusheld (AZD7442) Long-Acting Antibody Cocktail Description
AstraZeneca Evusheld AZD7442 is the first antibody combination (non-vaccine) modified to provide long-lasting protection up to 12 months potentially. AZD7442 is a combination of tixagevimab (AZD8895) and cilgavimab (AZD1061), derived from B-cells donated by convalescent patients after the SARS-CoV-2 betacoronavirus.
Tixagevimab and cilgavimab have been designed to attach to the spike protein of SARS-CoV-2 (the virus that causes COVID-19) at two different sites. The medicine is expected to stop the virus from entering the body's cells and causing infection by attaching it to the spike protein. Because the antibodies attach to different parts of the protein, using them in combination may be more effective than using either alone.
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. 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. In addition, 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 October 5, 2021, "Vulnerable populations such as the immunocompromised often aren't able to mount a protective response following vaccination and continue to be at risk of developing COVID-19. With this first global regulatory filing, we are one step closer to providing an additional option to help protect against COVID-19 alongside vaccines. We look forward to sharing AZD7442 data for the treatment of COVID-19 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.
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.
Evusheld (AZD7442) Long-Acting Antibody Cocktail 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.
On August 20, 2021, the Company announced AZD7442 PROVENT Phase III prophylaxis trial met the primary endpoint in preventing COVID-19: 77% reduced risk of developing symptomatic 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."
Located in Cambridge, UK, AstraZeneca is a global, science-led biopharmaceutical company.
Evusheld (AZD7442) Long-Acting Antibody Cocktail Dosage
In the TACKLE study, a 600mg IM dosage of AZD7442 was evaluated in 96 sites; 903 participants were randomized (1:1) to receive either AZD7442 (n = 452) or saline placebo (n = 451), administered in two separate, sequential IM injections. In another study, Arm 1 (n=approximately 3433) receive a single dose (× 2IM injections) of 300 mg of AZD7442
Evusheld (AZD7442) Long-Acting Antibody Cocktail 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 for up to 12 months. 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.
It is the first LAAB with Phase III data demonstrating a statistically significant reduction in the risk of developing symptomatic COVID-19 compared to placebo.
Additionally, it has also been proven to treat those who have symptoms, reducing the risk of developing severe COVID-19 or death (from any cause) by 67% compared to placebo.
Evusheld (AZD7442) Long-Acting Antibody Cocktail Side Effects
The LAAB was found well tolerated in phase 3 study, and preliminary analyses show adverse events were balanced between the placebo and AZD7442 groups.
Evusheld (AZD7442) Long-Acting Antibody Cocktail Availability
Discussions regarding supply agreements for AZD7442 are ongoing with the US Government as well as other governments around the world.
Evusheld (AZD7442) Long-Acting Antibody Cocktail News
October 14, 2021 - The EMA's human medicines committee confirmed it has started a rolling review of Evusheld (also known as AZD7442), a combination of two monoclonal antibodies which is being developed by AstraZeneca AB for the prevention of COVID-19 in adults.
October 11, 2021 - AstraZeneca announced positive high-level results from the TACKLE Phase III COVID-19 treatment trial showed AstraZeneca's AZD7442 LAAB combination achieved a statistically significant reduction in severe COVID-19 or death compared to placebo in non-hospitalized patients with mild-to-moderate symptomatic COVID-19. A total of 90% of participants enrolled were from populations at high risk of progression to severe COVID-19, including those with co-morbidities.
October 5, 2021 - AstraZeneca announced it had submitted a request to the US FDA for an Emergency Use Authorization (EUA) for AZD7442, its long-acting antibody (LAAB) combination, for prophylaxis of symptomatic COVID-19. If granted, AZD7442 would be the first LAAB to receive a EUA for COVID-19 prevention. The EUA request filing includes safety and efficacy data from the PROVENT and STORM CHASER Phase III trials and the Phase I trial.
September 27, 2021 - AstraZeneca announced today it will present data across its COVID-19 and respiratory syncytial virus pipeline at the 10th Annual IDWeek Virtual Conference. Data featuring AstraZeneca's investigational long-acting antibody programs – AZD7442 for COVID-19 and nirsevimab for RSV – as well as AZD1222, will be presented as three late-breaking oral presentations. Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said in a press release: "Our PROVENT Phase III data demonstrate AZD7442 may offer much-needed protection for vulnerable populations who may not mount an adequate immune response to COVID-19 vaccination."
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.
August 20, 2021 - A monoclonal antibody cocktail against the COVID-19 virus discovered at Vanderbilt University Medical Center and developed by AstraZeneca reduced the risk of symptoms in a study of immunocompromised and chronically ill adults later exposed to the virus by 77%.
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.
Evusheld (AZD7442) Long-Acting Antibody Cocktail Clinical Trials
AZD7442 has been involved in 8 clinical trials. Three of these trials are in the recruiting process.
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. AstraZeneca presented an abstract at IDWeek that this study hit the primary endpoint in preventing COVID-19.
Ongoing trials include TACKLE COVID-19, a Phase III mild-to-moderate COVID-19 outpatient treatment trial, and collaborator treatment trials in outpatient and hospitalized settings.
TACKLE is a Phase III, randomized, double-blind, placebo-controlled, multi-center trial assessing the safety and efficacy of a single 600mg IM dose of AZD7442 compared to placebo for the outpatient treatment of COVID-19. The trial was conducted in 96 sites in Brazil, Czech Republic, Germany, Hungary, Italy, Japan, Mexico, Poland, Russian Federation, Spain, Ukraine, UK and US. 903 participants were randomised (1:1) to receive either AZD7442 (n = 452) or saline placebo (n = 451), administered in two separate, sequential IM injections. Participants were adults 18 years-old and over who were non-hospitalised with mild-to-moderate COVID-19 and symptomatic for seven days or less. Participants had a documented laboratory-confirmed SARS-CoV-2 infection, as determined by a molecular test (antigen or nucleic acid) from any respiratory tract specimen (e.g. oropharyngeal, nasopharyngeal, or nasal swab or saliva) collected no more than three days prior to day one. The primary efficacy endpoint was the composite of either severe COVID-19 or death from any cause through day 29. Subjects will continue to be followed for 15 months. Approximately 13% of participants were 65 years and over. In addition, 90% had baseline co-morbidities and other characteristics that put them at high risk of progression to severe COVID-19, including cancer, diabetes, obesity, chronic lung disease or asthma, cardiovascular disease or immunosuppression. Approximately 62% were White/Caucasian, 4% Black/African-American, 6% Asian and 24% American Indian or Alaskan Native. Approximately 52% of participants were Hispanic/Latino.