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EvuSheld (AZD7442) Long-Acting Antibody

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May 27, 2022
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Evusheld (Tixagevimab plus Cilgavimab) Long-Acting Monoclonal Antibody Description For 2022

AstraZeneca Evusheld (AZD7442) (tixagevimab plus cilgavimab) is a Long-Acting monoclonal antibody combination that protects against severe COVID-19 for up to 12 months. Evusheld (AZD7442) contains infection-fighting proteins called monoclonal antibodies (mAbs). Antibodies are Y-shaped molecules produced naturally by the body's immune system that recognize, bind to, and neutralize specific viruses and other pathogens.

Evusheld (AZD7442) is a combination of tixagevimab (AZD8895) and cilgavimab (AZD1061), derived from B-cells donated by convalescent patients after SARS-CoV-2 beta coronavirus infections. Because the antibodies bind to different parts of the protein, using them in combination has been effective. Evusheld was designed to attach to the spike protein of SARS-CoV-2 (the virus that causes COVID-19) at two different sites and was optimized with half-life extension and reduced Fc receptor and complement C1q binding. As a result, the mAbs stop the coronavirus from entering the body's cells and causing infection. 

The Long-Acting Antibody (LAAB) Evusheld was engineered with AstraZeneca's proprietary half-life extension technology to increase the therapy's durability. AstraZeneca's LAABs mimic natural antibodies and have the potential to treat and prevent disease progression in patients already infected with the virus. In addition, the LAAB extension more than triples the durability of its action compared to conventional antibodies.

Discovered by Vanderbilt University Medical Center and licensed to AstraZeneca on Jun. 9, 2020. Evusheld was developed with support from the U.S. Government, including federal funds from the Department of Health and Human Services (HHS); Office of the Assistant Secretary for Preparedness and Response (ASPR); Biomedical Advanced Research and Development Authority (BARDA) 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.

The U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for Evusheld on Dec. 8, 2021, for 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 Dec. 29, 2021, the Outpatient administration guide for healthcare providers was updated. On Feb. 24, 2022, the FDA increased the initial authorized dose to 300 mg of tixagevimab and 300 mg of cilgavimab. Patients who have already received the previously authorized dose (150 mg of tixagevimab and 150 mg of cilgavimab) should receive an additional dose of 150 mg of tixagevimab and 150 mg of cilgavimab as soon as possible to raise their monoclonal antibody levels to those expected for patients receiving the higher dose.

The U.K. issued authorization on Mar. 17, 2022, as did the European Medicines Agency (EMA) on Mar. 24, 2022, followed by the EU EMEA/H/C/005788, and Canada on April 14, 2022. AstraZeneca AB was granted marketing authorization in the European Union.

On April 1, 2022, the U.S. NIH published an update to its Therapeutic Management of Nonhospitalized Adults With COVID-19. Several therapeutic options are now available to treat nonhospitalized adults with mild to moderate COVID-19 at high risk of disease progression. And FAQs were updated on April 1, 2022. As of April 13, 2022, Evusheld remains authorized.

On April 20, 2022, the NEJM published a peer-reviewed Original Article that reviewed a phase 3 study concluding, 'A single dose of AZD7442 had efficacy for preventing Covid-19, without evident safety concerns.' Symptomatic Covid-19 occurred in 8 of 3441 participants (0.2%) in the AZD7442 group; extended follow-up at a median of six months showed a relative risk reduction of 82.8% (95% CI, 65.8 to 91.4). Then on May 23, 2022, a non-peer-reviewed study - Further antibody escape by Omicron BA.4 and BA.5 from the vaccine and BA.1 serum - concluded 'Evusheld long-acting antibody combination retains neutralizing activity against Omicron variants.'

AstraZeneca (LSE/STO / Nasdaq: AZN) operates in over 100 countries, and its innovative medicines are used by millions of patients worldwide. Visit astrazeneca.com for additional information.

Evusheld Omicron BA.2 Subvariants

AstraZeneca announced on May 25, 2022, that Evusheld retains neutralization activity against the emerging Omicron BA.4 and BA.5 (BA.4/5) variants, according to new preclinical pseudovirus assay data from the University of Oxford.

The UK Health Security Agency is conducting tests to ascertain pre-exposure prophylaxis treatment Evusheld's effectiveness against SARS-CoV-2 virus BA.1 and BA.2 subvariants, the Pharmaceutical Journal stated on May 11, 2022. On May 13, 2022, the Blood Cancer UK stated 'After reviewing the available evidence, our position is that Evusheld should be made available for people who are not likely to mount an effective response to vaccines.'

As of May 15, 2022, the U.S. NIH OpenData Portal reported Evusheld in vitro Therapeutic Activity against SARS-CoV-2 virus variants. And the CDC's NowCast model estimates more recent proportions of circulating variants. And the CViSB Team at Scripps Research is tracking the prevalence of SARS-CoV-2 (hCoV-19) variants with lineage and mutation. And the U.K.'s CoVariants provide an overview of SARS-CoV-2 variants.

On March 28, 2022, AstraZeneca confirmed a growing body of evidence supporting the potential of Evusheld to protect against the BA.1, BA.1.1, and BA.2 Omicron SARS-CoV-2 subvariants. Recent non-peer-reviewed data from Washington University School of Medicine demonstrated that Evusheld retained potent neutralizing activity against the emerging and highly transmissible BA.2 subvariant. This study also showed Evusheld reduced viral burden and limited lung inflammation (in vivo) across all Omicron variants.

On March 21, 2022, AstraZeneca announced preclinical authentic 'live' virus data from the Washington University School of Medicine demonstrated that Evusheld retains potent neutralizing activity against the emerging and highly transmissible Omicron SARS-CoV-2 BA.2 subvariant. The non-peer-reviewed data also showed that Evusheld retains activity against Omicron BA.1 and BA.1.1.1 In addition, in vivo data generated using mice infected with Omicron BA.1, BA.1.1, and BA.2 demonstrated that Evusheld significantly reduced the viral burden and limited lung inflammation for all three subvariants.

The NEJM published on March 9, 2022, a Correspondance: Efficacy of Antiviral Agents against the SARS-CoV-2 Omicron Subvariant BA.2. Clinical studies are warranted to determine whether these antiviral therapies are effective against omicron/BA.2 infections. And a previous Correspondence from researchers in Japan on Jan. 26, 2022, reported 'The tixagevimab–cilgavimab combination inhibited beta, gamma, and omicron. In addition, the FRNT50 values of this combination were higher by a factor of 24.8 to 142.9 for omicron than for beta or gamma, respectively.'

On Dec. 23, 2021, AstraZeneca announced that Evusheld retains neutralizing activity against the Omicron variant in Oxford and Washington University studies. According to data published on Dec. 17, 2021, non-peer-reviewed studies found AstraZeneca's Evusheld retained neutralizing activity against the Omicron 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 Availability

On Feb. 11, 2022, the U.S. Defense Department awarded AstraZeneca an $855 million contract to manufacture, distribute, and store AZD7442 (Evusheld) for the general population. Previously AstraZeneca agreed to supply the US government with 700,000 additional doses of Evusheld.

AstraZeneca received Emergency Use Authorization for EVUSHELD from the U.S. FDA on December 8, 2021. Since then,1,248,336 Evusheld doses have been shipped in the U.S. On May 2, 2022, the U.S. HHS's Assistant Secretary for Preparedness and Response confirmed (199,992) that additional doses of Evusheld would be distributed. The HHS oversees the allocation and distribution of Evusheld in the U.S.

On Nov. 14, 2021, Bahrain became the first country to Approve Evusheld, followed by Abu DhabiAustralia, Belgium, CanadaEgypt, France, IsraelSpainSouth Korea, and recently the U.K. and Malaysia

Evusheld Payments

During the COVID-19 Public Health Emergency, the U.S. CMS pays for mAbs infusions (consistent with 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 History

In a Nature publication in July 2020, the LAAB was 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."

Under the terms of the licensing agreement with Vanderbilt University, AstraZeneca will pay single-digit royalties on future net sales.

Located in Cambridge, UK, and Delaware, AstraZeneca is a global, science-led biopharmaceutical company. Note: The Brand Institute partnered with AstraZeneca in developing the brand name EVUSHELD™.

Evusheld 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 U.S., the FDA suggests the dosage of 300mg of tixagevimab and 300mg of cilgavimab. And in Europe, the recommended dosage of Evusheld is 150mg of tixagevimab and 150mg of cilgavimab, administered as two separate sequential intramuscular injections.

Evusheld Indication

The Evusheld product is 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.

The JAMA Network published a Medical Lette on January 25, 2022, in a double-blind trial, one-time IM administration of the antibodies decreased the incidence of symptomatic COVID-19 compared to placebo in at-risk adults for 6 months. And Evusheld (tixagevimab and cilgavimab) can be administered to eligible patients every six months while SARS-CoV-2 is in circulation.

On Feb. 1, 2022, the NIH COVID-19 Treatment Guidelines Panel recommended using tixagevimab plus cilgavimab as SARS-CoV-2 PrEP for adults and adolescents (aged ≥12 years and weighing ≥40 kg) who do not have SARS-CoV-2 infection, who have not been recently exposed to an individual with SARS-CoV-2 infection.

Evusheld Adolescents 

Australia granted Provisional Determination to Astrazenecas's Evusheld for adolescents (12+) on January 4, 2022. As did Europe on March 28, 2022.

Evusheld Side Effects

The most common adverse effects of tixagevimab plus cilgavimab in the PROVENT study were headache (6%) and fatigue (4%). Rates of overall and serious adverse events in the antibody and placebo groups were similar. In the post-hoc analysis of PROVENT, the incidence of serious cardiac adverse events (myocardial infarction, cardiac failure, arrhythmia) was higher in the antibody group than in the placebo group (0.6% vs 0.2%). One person who received the antibodies died of myocardial infarction. There was no clear temporal relationship between antibody administration and cardiac adverse events.

Evusheld Sales

On April 29, 2022, AstraZeneca reported first-quarter 2022 results for Evusheld of $469 million.

On February 10, 2022, AstraZeneca reported its financial disclosures, which announced minimal revenues from Evusheld sales in 2021. 

Evusheld News

May 23, 2022 - A non-peer-reviewed study published by the University of Oxford confirmed AZD7442 retains neutralization activity against the emerging Omicron BA.4 and BA.5 (BA.4/5) variants.

May 17, 2022 - RQ Bio announced a successful licensing deal with AstraZeneca for RQ Bio's existing mAbs against SARS-CoV-2. Under the terms of the agreement, RQ Bio has granted AstraZeneca an exclusive worldwide license to develop, manufacture, and commercialize RQ Bio's existing early-stage mAbs against SARS-CoV-2 and a right of first refusal to take an exclusive license in respect of any additional mAbs against SARS-CoV-2.

May 13, 2022 - The Malaysian Ministry of Health announced the Drug Control Authority's conditional approval of the Evusheld mAbs.

May 5, 2022 - Chief Public Health Officer Dr. Heather Morrison said told CBC News, that Canada's PEI province will get 100 doses of the antibody therapy Evusheld.

May 5, 2022 - "The key to ending the COVID-19 pandemic (in New Brunswick) is protecting as many people as possible against infection, including those who may need an additional layer of protection to prevent COVID-19 than vaccines alone can provide," said Kiersten Combs. The approval of Evusheld, she said, is "an important step along this journey."

May 5, 2022 - Taylor Francis Online published: COVID-19 vaccine-associated transverse myelitis-Evusheld as an option when vaccination is not recommended due to severe adverse events. 'We report the safe administration of Evusheld to a patient who experienced transverse myelitis 11 months previously as a result of receiving the Moderna mRNA vaccine. This patient has experienced no adverse events to Evusheld.'

April 21, 2022 - AstraZeneca US announced pre-exposure prophylaxis phase 3 clinical trial found up to 83% reduction of symptomatic COVID-19 risk, with no severe disease or COVID-19-related deaths in the EVUSHELD group.

April 20, 2022 - The New England Journal of Medicine published the findings from a phase 3 randomized clinical trial focused on the monoclonal antibody combination tixagevimab-cilgavimab (Evusheld) - which reduced the risk of symptomatic COVID-19 infection by 83% over placebo at a median follow-up of 6 months.

April 14, 2022 - Canada confirmed Evusheld was authorized, as did the U.K. in March 2022.

April 14, 2022 - The AMA published an article: 3 tips for doctors on using Evusheld for COVID-19 protection.

April 13, 2022 - CNN published an Opinion: There's a drug to protect the most vulnerable from Covid-19. Why is it so hard to get?

March 28, 2022 - AstraZeneca plc announced Evusheld, a long-acting antibody combination, was approved in the EU for pre-exposure prophylaxis of COVID-19 in a broad population.

March 19, 2022 - A non-peer-reviewed study: Breakthrough Covid-19 cases despite Evusheld prophylaxis in kidney transplant recipients - Preexposure prophylaxis with a 'lower dose' of Evusheld provided 90% protection KTRs against Omicron. Of the 416 KTRs who received intramuscular prophylactic injections of Evusheld (150 mg tixagevimab and 150 mg cilgavimab), 39 (9.4%) developed COVID-19.

March 18, 2022 - A non-peer-reviewed study - Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains - demonstrates the resilience of S309 and AZD7442 mAbs against emerging SARS-CoV-2 variant strains in mice and provide insight into the relationship between loss of antibody neutralization potency and retained protection in vivo.

March 17, 2022 - The U.K.'s decision to grant approval for Evusheld was endorsed by the government's independent expert scientific advisory body, the Commission on Human Medicines, after carefully reviewing the evidence.

March 15, 2022 - Reuters reported the EMA had begun reviewing Evusheld for use in Europe.

March 14, 2022 - HealthDay reported according to NEJM findings on March 9, 2022, the most effective antibody treatment against the BA.2 variant was Evusheld.

March 6, 2022 - The New York Times reported the U.S. administration has purchased 1.7 million doses and had nearly 650,000 doses ready for distribution as of this past week. However, the government's distribution disclosure indicates 49,992 doses were sent to states, territories, or agencies.

March 3, 2022 - The EMA Tweeted: The rolling review of the monoclonal antibodies Evusheld has progressed. In the next few weeks, we could move towards the submission of a marketing authorization application.

February 24, 2022 - The U.S. FDA announced changes to Evusheld's dosing schedule - the initial authorized dose is 300 mg of tixagevimab and 300 mg of cilgavimab.

February 11, 2022 - The U.S. government (DoD) awarded AstraZeneca an $855,000,000 modification (P00005) to contract W911QY-20-C-0119 for the manufacture, distribution, and storage of AZD7442 to treat COVID-19 in the general population. Work will be performed in various locations, with an estimated completion date of March 31, 2023.

February 4, 2022 - ABC27 reported: "If you get a call about Evusheld, say yes," said Tami Minnier, Chief Quality & Operational Excellence Office at UPMC. Evushled is offered at UPMC locations in the Midstate.

January 26, 2022 - Local media reported Egypt's Ministry of Health and Population will soon receive its first shipment of Evusheld. The shipment includes enough doses of Evusheld to treat 50,000 people and will be distributed amongst hospitals.

January 25, 2022 - NPR wrote an article: Hospitals use a lottery to allocate scarce COVID drugs for the immunocompromised.

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 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, and 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.