AstraZeneca recently announced that the European Commission (EC) has approved its long-acting antibody therapy Evusheld (tesaglizumab in combination with cilgravizumab, formerly AZD7442) for the treatment of adults and adolescents with severe COVID-19 who do not require supplemental oxygen. The recommended dose is 150 mg of tesaglizumab plus 150 mg of cilgravizumab, with the 2 antibodies administered separately, as a continuous intramuscular injection.
In March 2022, Evusheld was approved in the EU for pre-exposure prophylaxis (PrEP) of SARS-CoV-2 in a broad population of adults and adolescents (age ≥ 12 years, weight ≥ 40 kg). There is evidence that Evusheld can significantly reduce the risk of symptomatic COVID-19 compared to placebo in high-risk populations, with protection lasting for at least 6 months.
With this approval, Evusheld becomes the only long-acting antibody combination therapy available in Europe for both PrEP and treatment against COVID-19 and will protect more people from this devastating disease.
This approval is based on the results of the TACKLE Phase 3 COVID-19 treatment trial, conducted in adult ambulatory patients with mild to moderate COVID-19 with symptoms lasting no more than 7 days, where 90% of participants were at a high risk of developing severe COVID-19 due to comorbidities or age. A single intramuscular (IM) dose of Evusheld proved clinically and statistically substantially protective compared to placebo, dramatically lowering the probability of progression to severe COVID-19 or death from any cause. More favorable outcomes were obtained when Evusheld was given early in the course of the disease.
Specifically by day 29, Evusheld significantly reduced the relative risk of progression to severe COVID-19 or death (from any cause) by 88%, 67%, and 50%, respectively, compared to placebo in patients treated within 3, 5, and 7 days of symptom onset. Evusheld was generally well-tolerated in this trial.
Michel Goldman, Ph.D., former executive director of the European Innovative Medicines Initiative and professor at the Institute for Interdisciplinary Innovation in Health Care at the Université Libre de Bruxelles, said, “Many people, including immunocompromised people, the elderly and people with underlying diseases who are infected with the new coronavirus, are at high risk of serious illness, hospitalization and death. Evusheld, available in a simple intramuscular formulation, will now be a much-needed, new COVID-19 treatment option for these vulnerable populations.”
Evusheld is a long-acting antibody therapy made up of 2 monoclonal antibodies, tixagevimab (AZD8895) and cilgavimab (AZD1061), derived from B cells donated by patients recovering from SARS-CoV-2 infection. The 2 monoclonal antibodies were discovered by Vanderbilt University Medical Center and licensed to AstraZeneca in June 2020. Tixagevimab and cilgavimab target 2 different sites of the SARS-CoV-2 spine protein, respectively, and have synergistic effects that reduce the risk of viral mutation escape.
AstraZeneca has optimized these 2 monoclonal antibodies to have a extended half-life, reduced Fc receptor and complement C1q binding, and more than 3-fold longer half-life compared to ordinary antibodies. Reduced Fc receptor binding is intended to lessen the likelihood of antibody-dependent enhancement (ADE) of disease, which occurs when virus-specific antibodies promote rather than inhibit infection and/or disease.
In March 2022, Evusheld was approved in the EU for a prophylactic indication: PrEP for SARS-CoV-2 in a broad population of adults and adolescents (age ≥ 12 years, weight ≥ 40 kg). Data from the PROVENT Phase 3 PrEP trial showed that Evusheld significantly reduced the risk of developing symptomatic COVID-19, with protection lasting for at least 6 months. Specifically: at preliminary analysis, Evusheld prophylaxis reduced the risk of symptomatic COVID-19 by 77% compared to placebo; at a median 6-month analysis, the risk was reduced by 83%, indicating a protective effect lasting at least 6 months. Evusheld was generally well tolerated in this trial.