Evusheld (Tixagevimab plus Cilgavimab) Long-Acting Antibody Description
AstraZeneca Evusheld (AZD7442) (tixagevimab plus cilgavimab) is a Long-Acting antibody combination that provides long-lasting protection for up to 12 months. AZD7442 is a combination of tixagevimab (AZD8895) and cilgavimab (AZD1061), derived from B-cells donated by convalescent patients after the SARS-CoV-2 betacoronavirus. Because the antibodies bind to other parts of the protein, using them in combination may be more effective than using either alone.
Evusheld was designed to attach to the spike protein of SARS-CoV-2 (the virus that causes COVID-19) at two different sites. In addition, Evusheld (AZD7442) contains infection-fighting proteins called monoclonal antibodies. As a result, the medicine is expected to stop the virus from entering the body's cells and causing infection. Antibodies are Y-shaped molecules produced naturally by the body's immune system. They recognize, bind to, and neutralize specific viruses and other pathogens.
The Long-Acting Antibody (LAAB) Evusheld was engineered with AstraZeneca's proprietary half-life extension technology to increase the therapy's durability up to 12 months following a single administration. The human monoclonal antibodies bind to distinct sites on the SARS-CoV-2 spike protein and were optimized 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.
AstraZeneca's LAABs mimic natural antibodies and have the potential to treat and prevent disease progression in patients already infected with the virus and be given as a preventative intervention before exposure to the virus.
Discovered by Vanderbilt University Medical Center and licensed to AstraZeneca on June 9, 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.
The U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for Evusheld on December 8, 2021, for healthcare providers, patients, and caregivers. The EUA allows this combination to be used as pre-exposure prophylaxis (PrEP) in certain individuals who, if infected, are at high risk of progressing to severe COVID-19. And on December 29, 2021, the Outpatient administration guide for healthcare providers was updated. The U.S. NIH published an update to the COVID-19 Treatment Guidelines Panel's Statement on Tixagevimab Plus Cilgavimab (Evusheld) for Pre-Exposure Prophylaxis for SARS-CoV-2 Infection on January 5, 2022.
Evusheld (Tixagevimab plus Cilgavimab) was development has obtained support from the U.S. 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 and SARS-CoV-2 Virus Variants (Omicron)
As of January 17, 2022, the U.S. NIH OpenData Portal reported Evusheld (Tixagevimab plus Cilgavimab) in vitro Therapeutic Activity against SARS-CoV-2 virus variants. And the CViSB Team at Scripps Research is tracking the prevalence of SARS-CoV-2 (hCoV-19) variants with lineage and mutation.
In light of recent National Institutes of Health clinical guidelines published on Dec. 30, 2021, and the significant variability in the prevalence of the Omicron Variant of Concern (VOC), all states and territories can continue to order monoclonal antibody products from HHS based on allocated amounts for clinically appropriate use.
AstraZeneca announced on December 23, 2021, Evusheld retains neutralizing activity against the Omicron variant in studies from Oxford and Washington Universities. None of the Omicron binding site substitutions relevant to Evusheld tested to date in preclinical assays have been associated with escape from Evusheld neutralization. In vitro findings demonstrate Evusheld neutralizes other recent emergent SARS-CoV-2 viral variants, including the Delta and Mu variants.
According to data published on December 17, 2021, non-peer-reviewed studies found AstraZeneca's Evusheld retained neutralizing activity against the Omicron SARS-CoV-2 variant (B.1.1.529). EVUSHELD's Inhibitory Concentration 50 (IC50), a measure of neutralizing potency of an antibody, was 273 ng/ml and 147 ng/ml in the Oxford and Washington University studies, respectively.
Evusheld (Tixagevimab plus Cilgavimab) Long-Acting Antibody Availability
In the U.S., AstraZeneca received Emergency Use Authorization (EUA) for EVUSHELD (tixagevimab co-packaged with cilgavimab) from the U.S. FDA on December 8, 2021. Since then, about 270,000 doses of Evusheld have been shipped in the U.S. On January 17, 2022, the U.S. HHS's Assistant Secretary for Preparedness and Response confirmed 73,752 doses of Evusheld were distributed to states such as California, Kentucky, Virginia, South Carolina, Pennsylvania, Michigan, and Texas. The HHS oversees the allocation and distribution of this product in the U.S.
AstraZeneca recently agreed to supply the US government with 700,000 additional doses of Evusheld.
In Europe, the EMA began a rolling review of Evusheld developed by AstraZeneca AB on October 14, 2021, to prevent COVID-19 in adults. On November 14, 2021, Bahrain became the first country to Approve Evusheld, followed by Abu Dhabi, Australia, and South Korea.
Evusheld (Tixagevimab plus Cilgavimab) Payment in the U.S.
During the COVID-19 public health emergency, the U.S. CMS pays for mAbs infusions (when furnished consistent with their respective EUAs) the same way it covers and pays for COVID-19 vaccines. CMS identified specific code(s) for each COVID-19 monoclonal antibody product and specific administration codes (M0220, M0221) for Medicare payment.
Evusheld (Tixagevimab plus Cilgavimab) Long-Acting Antibody History
In a Nature publication in July 2020, LAABs were shown in preclinical 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 (tixagevimab and cilgavimab) 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.' 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, U.S., and principal investigator of 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, and in Delaware, AstraZeneca is a global, science-led biopharmaceutical company. Note: The Brand Institute partnered with AstraZeneca in developing the brand name EVUSHELD™.
Evusheld (Tixagevimab plus Cilgavimab) Long-Acting Antibody Dosage
EVUSHELD consists of two investigational medicines, tixagevimab, and cilgavimab. Patients receive one dose of EVUSHELD, composed of two separate injections, given by a healthcare provider as two intramuscular injections. They are usually given one after the other, one into each buttock.
In the TACKLE study, a 600mg I.M. 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 I.M. injections. In another study, Arm 1 (n=approximately 3433) receive a single dose (× 2IM injections) of 300 mg of AZD7442. The ongoing PROVENT phase 3 clinical trial evaluates one 300mg I.M. dose of AZD7442 to reduce the risk of developing symptomatic COVID-19.
Evusheld (Tixagevimab plus Cilgavimab) Long-Acting Antibody Indication
Antibodies are engineered to resist breakdown in cells. This can prolong the time they last in the circulation, increasing the time the antibodies could protect against viruses and other pathogens. The Evusheld product is only authorized for those individuals who are not currently infected with the SARS-CoV-2 coronavirus and who have not recently been exposed to an individual infected with SARS-CoV-2. The authorization also requires that individuals either have moderate to severely compromised immune systems due to a medical condition or due to taking immunosuppressive medications or treatments and may not mount an adequate immune response to COVID-19 vaccination, or a history of severe adverse reactions to a COVID-19 vaccine and/or component(s) of those vaccines. In addition, individuals who have received a COVID-19 vaccine, EVUSHELD, should be administered at least two weeks after vaccination.
Evusheld (Tixagevimab plus Cilgavimab) Long-Acting Antibody Indication for Adolescents
Australia granted Provisional Determination to Astrazenecas's Evusheld for adolescents on January 4, 2022. This new determination now includes the prevention and treatment of COVID-19 in individuals aged 12 years and older.
Evusheld (Tixagevimab plus Cilgavimab) Long-Acting Antibody Adverse Effects
The most common adverse events (all grades, incidence ≥3%) are headache, fatigue, and cough. The LAAB was well tolerated in the phase 3 study, and preliminary analyses show that adverse events were balanced between the placebo and AZD7442 groups.
Evusheld Contractual Obligations
Under the terms of the licensing agreement with Vanderbilt University, AstraZeneca will pay single-digit royalties on future net sales.
Evusheld (Tixagevimab plus Cilgavimab) Long-Acting Antibody News
January 12, 2022 - CNN reported the U.S. government is "in the process of ordering another half-million course of AstraZeneca's Evusheld, Covid-19 response coordinator Jeff Zients said at Wednesday's Covid-19 briefing.
January 4, 2022 - In Pennsylvania, UPMC, Penn State, Penn Medicine Lancaster, and WellSpan Health have all received doses of the drug. UPMC said it has received 456 doses for at least 800,000 patients that qualify. "So we can treat the sickest of the sick."
December 23, 2021 - AstraZeneca announced EVUSHELD retained neutralization activity against the Omicron SARS-CoV-2 variant, according to new authentic 'live' virus neutralization data from the University College Oxford, UK, and Washington University School of Medicine, St. Louis, US.
December 17, 2021 - Florida's governor stated during an interview in Ocala Evusheld would soon become available. There is currently a standing order in Florida signed by the State Surgeon General that allows patients to receive this treatment without a prescription or referral if administered by an eligible health care provider.
December 16, 2021 - AstraZeneca today announced EVUSHELD retained neutralizing activity against the Omicron SARS-CoV-2 variant (B.1.1.529), according to new preclinical data.
December 14, 2021 - Samsung Biologics will begin manufacturing AstraZeneca's COVID-19 antibody combination Evusheld.
December 8, 2021 - AstraZeneca confirmed today Evusheld, a long-acting antibody combination, has received emergency use authorization in the U.S. for the pre-exposure prophylaxis of COVID-19, with first doses expected to become available very soon.
December 8, 2021 - The U.S. FDA issued a EUA for Evusheld (tixagevimab co-packaged with cilgavimab).
November 19, 2021 - The BMJ reported AstraZeneca's AZD7442 long-lasting experimental treatment effectively prevents and reduces severe COVID-19 illness.
November 18, 2021 - AstraZeneca reported new data from the AZD7442 COVID-19 PROVENT prevention and TACKLE outpatient treatment Phase III trials both showed robust efficacy from a one-time intramuscular (I.M.) dose of the long-acting antibody (LAAB) combination. In addition, an analysis of the ongoing PROVENT trial evaluating a median of six months of participant follow-up, one 300mg I.M. dose of AZD7442 reduced the risk of developing symptomatic COVID-19 compared to placebo by 83%.
November 9, 2021 - BioSpace reported AstraZeneca plans to create a separate division for vaccines and antibody therapies. The focus will be on its COVID-19 vaccine developed with the University of Oxford and other COVID-19 antibody treatments.
October 14, 2021 - The EMA's human medicines committee started a rolling review of Evusheld (AZD7442) being developed by AstraZeneca AB to prevent 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 U.S. FDA for an Emergency Use Authorization for AZD7442, its long-acting antibody combination, to prevent 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. In addition, 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.
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.
February 8, 2021 - The U.S. NIH published: Clinical trial in hospitalized COVID-19 patients evaluates long-acting antibody therapy.
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.
June 9, 2020 - Vanderbilt University Medical Center discovered the human monoclonal antibodies and licensed them to AstraZeneca. Under the terms of the licensing agreement with Vanderbilt, AstraZeneca will pay single-digit royalties on future net sales.
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 Clinical Trials
Visit AstraZeneca for more sponsored trial information. Based on the results of PROVENT (NCT04625725), the U.S. FDA issued an Emergency Use Authorization on December 8, 2021, for the anti-SARS-CoV-2 monoclonal antibodies tixagevimab plus cilgavimab (Evusheld). 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 I.M. 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.
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). In addition, 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.
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 I.M. dose of AZD7442 compared to placebo for the outpatient treatment COVID-19. The trial was conducted in 96 sites in Brazil, Czech Republic, Germany, Hungary, Italy, Japan, Mexico, Poland, Russian Federation, Spain, Ukraine, U.K., and U.S. 903 participants were randomized (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-hospitalized 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 before day one. The primary efficacy endpoint was the composite of severe COVID-19 or death from any cause until 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. About 52% of participants were Hispanic/Latino.