EVUSHELD™ RECEIVES HEALTH CANADA APPROVAL FOR TREATMENT OF COVID-19

Evusheld is the first long-acting antibody (LAAB) combination to receive Health Canada authorization for both the prevention and treatment of COVID-19

Evusheld significantly reduced risk of severe COVID-19 or death in TACKLE Phase III treatment trial

MISSISSAUGA, ON, Oct. 18, 2022 /CNW/ - AstraZeneca's Evusheld™ (tixagevimab and cilgavimab), a long-acting antibody combination has received a Notice of Compliance from Health Canada for the treatment of mild to moderate COVID-19 in adults and adolescents (≥12 years of age weighing at least 40 kg).ⁱ This approval follows AstraZeneca's announcement in April that Evusheld had been approved as a preventative treatment for COVID-19 and is already available across Canada.

"Certain Canadians continue to be vulnerable to poor outcomes from COVID-19 and having a new treatment option in our arsenal, particularly one that is given as a single dose, is especially welcome news as we move into the winter months when we expect case counts to rise," said Dr. Zain Chagla, Associate Professor, Medicine, Faculty of Health Sciences, McMaster University. "Studies show long-acting antibodies can play an effective role in both treatment and prevention of COVID-19. Evusheld has already made an impact preventing infection in vulnerable populations, such as the immune-compromised, and now has the potential to play an important role in COVID-19 treatment, making sure that high risk patients have even more access to therapeutic options."

The approval by Health Canada was based on results from the TACKLE Phase III treatment trial, which demonstrated reduced risk of severe COVID-19 or death in high-risk patients.ⁱⁱ

"Today's approval marks an important step in our ongoing journey to reduce the impact of COVID-19 on the lives of Canadians," said Kiersten Combs, President of AstraZeneca Canada. "Evusheld is now the only long-acting antibody combination approved for both prevention and treatment of COVID-19 in Canada, allowing us to help protect even more people who are immune-compromised and remain most vulnerable to this devastating disease."

In TACKLE, one intramuscular (IM) dose of Evusheld provided clinically and statistically significant protection against progression to severe COVID-19 or death from any cause compared to placebo. Evusheld treatment earlier in the disease course led to more favourable outcomes. TACKLE was conducted in non-hospitalized adults with mild-to-moderate COVID-19 who were symptomatic for seven days or less. 90% of trial participants were at high risk of progression to severe COVID-19 due to co-morbidities or age. Evusheld was generally well tolerated in the trial.ⁱⁱ The recommended dose of Evusheld for treatment in Canada is 300mg of tixagevimab and 300mg of cilgavimab, administered as two separate, sequential IM injections.

Evusheld has been shown to retain in vitro neutralization activity against the main Omicron variants currently circulating globally, including BA.5.^{iii iv}

Evusheld is the only long-acting antibody combination with positive Phase III data in the prevention and treatment of COVID-19.^{v vi}

About TACKLE
TACKLE is a Phase III, randomized, double-blind, placebo-controlled, multi-centre trial assessing the safety and efficacy of a single 600mg IM dose of Evusheld (300mg each of cilgavimab and tixagevimab) compared to placebo for the treatment of mild-to-moderate COVID-19. The trial was conducted in 95 sites in the US, Latin America, Europe and Japan. 903 participants were randomized (1:1) to receive either Evusheld (n = 452) or saline placebo (n = 451), administered in two separate, sequential IM injections.

Detailed results from TACKLE, published in The Lancet Respiratory Medicine, showed Evusheld significantly reduced the relative risk of progressing to severe COVID-19 or death (from any cause) by 50% (95% confidence interval [CI] 15, 71; p=0.010) through day 29 compared to placebo in non-hospitalized patients with mild-to-moderate COVID-19 who were symptomatic for seven days or less, the trial's primary endpoint. In pre-specified analyses, the risk reduction was 67% (95% CI 31, 84) compared with placebo when non-hospitalized participants received Evusheld within five days of symptom onset.ⁱⁱ

About Evusheld
Evusheld, formerly known as AZD7442, is a combination of two long-acting antibodies – tixagevimab (AZD8895) and cilgavimab (AZD1061) – derived from B-cells donated by convalescent patients after SARS-CoV-2 infection. Discovered by Vanderbilt University Medical Center and licensed to AstraZeneca in June 2020, the human monoclonal antibodies bind to distinct sites on the SARS-CoV-2 spike protein^vii and were optimized by AstraZeneca with half-life extension and reduction of Fc effector function and complement C1q binding. The half-life extension more than triples the durability of its action compared to conventional antibodies;^{viii ix x} data from the Phase III PROVENT trial show protection lasting at least six months.^{i xi} The reduced Fc effector function 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.^xii

Evusheld is authorized for use for pre-exposure prophylaxis (prevention) of COVID-19 in Canada, the US (emergency use), EU, Japan and many other countries. Evusheld is approved for treatment of those with risk factors for severe SARS-CoV-2 infection in the EU and Japan (emergency use).

About AstraZeneca Canada
AstraZeneca is a global, innovation-driven biopharmaceutical business with a focus on the discovery, development, and commercialization of medicines that transform lives. Our core scientific focus is in the areas of Cardiovascular, Renal and Metabolic (CVRM) disease; Oncology; Rare Disease; Respiratory & Immunology; and Vaccine & Immune Therapies. AstraZeneca operates in more than 100 countries and its innovative medicines are used by millions of patients worldwide. In Canada, the company employs more than 1,200 people across Canada, including roughly 700 employees at our head office and clinical research hub in Mississauga, Ontario. For more information, please visit the company's website at www.astrazeneca.ca.

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References

ⁱ Evusheld Canadian Product Monograph. Available at: https://www.astrazeneca.ca/en/our-medicines.html. [Last accessed: October 2022].

ⁱⁱ Montgomery H, et al. Efficacy and Safety of Intramuscular Administration of AZD7442 (Tixagevimab/Cilgavimab) for Early Outpatient Treatment of COVID-19: The TACKLE Phase 3 Randomised Controlled Trial. Lancet Respir Med. Published online June 7, 2022. doi.org/10.1016/S2213-2600(22)00180-1.

ⁱⁱⁱ US Food and Drug Administration FACT SHEET FOR HEALTHCARE PROVIDERS: EMERGENCY USE AUTHORIZATION FOR EVUSHELD^TM (Tixagevimab Co-Packaged with Cilgavimab). Available at: https://www.fda.gov/media/154701/download [Last accessed: September 2022].

^iv Vector Engineering Lab et al. COVID CG. Available at: https://covidcg.org/ [Last accessed: September 2022]

^v AstraZeneca news release. AZD7442 PROVENT Phase III prophylaxis trial met primary endpoint in preventing COVID-19. Available at: https://www.astrazeneca.com/media-centre/press-releases/2021/azd7442-prophylaxis-trial-met-primary-endpoint.html. [Last accessed: September 2022].

^vi AstraZeneca news release. Evusheld reduced risk of developing severe COVID-19 or death in TACKLE Phase III outpatient treatment trial. Available at: https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/Evusheld-phiii-trial-positive-in-covid-outpatients.html. [Last accessed: September 2022].

^vii Dong J, et al. Genetic and structural basis for recognition of SARS-CoV-2 spike protein by a two-antibody cocktail. Nat Microbiol. 2021;6(10):1233-1244.

^viii 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.

^ix 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.

^x 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.

^xi 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: September 2022].

^xii van Erp EA, et al. Fc-mediated antibody effector functions during respiratory syncytial virus infection and disease. Front Immunol. 2019; 10: 548.

SOURCE AstraZeneca Canada Inc.

Carlo Mastrangelo, AstraZeneca Canada, E-mail: [email protected]; Mary-Anne Cedrone, AstraZeneca Canada, E-mail: [email protected]