The FDA has withdrawn the emergency use authorization (EUA) for AstraZeneca’s Evusheld (tixagevimab with cilgavimab) as a COVID-19 pre-exposure prophylaxis owing to the emergence of new variants.
Evusheld has been found to be ineffective against several omicron subvariants, including BQ.1, BQ.1.1, BF.7, BF.11, BA.5.2.6, BA.4.6, BA.2.75.2, XBB, and XBB.1.5.1.
The XBB.1.5 subvariant is becoming more prevalent in the U.S., accounting for approximately half of COVID-19 infections in the country.
In 2022, AstraZeneca announced that Evusheld reduced the risk of developing symptomatic COVID-19 by about three-quarters in a Phase 3 study.
In 2022, AstraZeneca revealed the results of a Phase 3 study, showing that Evusheld reduced the likelihood of experiencing symptomatic COVID-19 by roughly 75%. The results were summarized in NEJM in an article noting that the antibody cocktail retained some protection against an early omicron variant.
From Evusheld to AZD5156
To address the matter, AstraZeneca is conducting the Supernova Phase 1/2 clinical study to evaluate a new long-acting antibody (LAAB), AZD5156, for COVID-19 pre-exposure prophylaxis in immunocompromised individuals.
The randomized, double-blind Supernova trial is comparing the safety and effectiveness of the new LAAB, known as AZD5156, against Evusheld (AZD7442) and placebo. The study is recruiting around 3,200 immunocompromised individuals aged 12 years or older who weigh at least 40 kg in approximately 20 countries.
Lab studies have shown that AZD5156 can neutralize known SARS-CoV-2 variants, including those resistant to other monoclonal antibodies. AstraZeneca intends to commercialize AZD5156 in the latter half of 2023, pending regulatory approvals.
The company estimates that around 2% of the global population is at an elevated risk of COVID-19 due to an inadequate vaccine response and may benefit from COVID-19 monoclonal antibodies.
AstraZeneca facing financial pressures
AstraZeneca’s shares remained stable after the announcement, dropping by 0.32% to £10,610.00. However, analysts at Stifel have warned that the company may face a challenging year in 2023, with the potential loss of $3 billion in sales of its COVID-19 products between 2022 and 2023. While a decrease in sales of AstraZeneca’s Vaxzevria vaccine was expected, Evusheld’s struggles against new variants were not. The company’s portfolio may also face increasing generic competition, potentially leading to a global sales loss of over $1 billion. Additionally, Stifel noted that AstraZeneca may face tax increases.
Several antibodies introduced over the course of the pandemic have failed to offer sustained efficacy against COVID-19 as the virus behind the disease mutates.
Several antibodies introduced during the pandemic have failed to maintain their efficacy against COVID-19 as the virus continues to mutate. In April 2021, the FDA revoked emergency use of Lilly’s bamlanivimab. The agency also limited the use of Regeneron’s REGEN-COV (casirivimab and imdevimab) and Lilly’s bamlanivimab and etesevimab antibody cocktail in early 2022.