Cilgavimab

SARS-CoV-2, the causative agent of COVID-19, enters cells via the interaction between the trimeric spike (S) glycoprotein and host cell angiotensin-converting enzyme 2 (ACE2). Blocking the interaction between the receptor-binding domain (RBD) of the S1 subunit and ACE2 inhibits viral host cell entry; animal studies indicate that antibodies capable of blocking this interaction reduce viral load and improve clinical symptoms of infection. Cilgavimab (formerly AZD1061) is a recombinant monoclonal antibody produced in Chinese hamster ovary (CHO) cells derived from a neutralizing antibody isolated from a patient with a natural history of SARS-CoV-2 infection and modified through targeted amino acid substitutions to exhibit an extended (~85-day) half-life. As the RBD binding site of cilgavimab does not overlap with that of tixagevimab, the two can be administered to synergistically impair SARS-CoV-2 infection in individuals who may be exposed to the virus.

Cilgavimab is not approved for any indication by the FDA. Cilgavimab, in combination with tixagevimab, was issued an FDA emergency use authorization (EUA) on December 9, 2021, for the pre-exposure prophylaxis of COVID-19 in individuals at increased risk for whom vaccination is not recommended. The combination is co-packaged and available under the name EVUSHELD (formerly AZD7442). EVUSHELD was granted marketing authorization by the EMA on March 28, 2022, and was approved in Canada soon after, on April 14, 2022.

In October 2022, the FDA and Health Canada released safety alerts regarding the risk of developing COVID-19 when exposed to SARS-CoV-2 variants not neutralized by EVUSHELD. Certain SARS-CoV-2 Omicron subvariants may be associated with resistance to monoclonal antibodies, such as EVUSHELD. The FDA and Health Canada advise healthcare providers to inform patients of this risk.

Cilgavimab has been issued an emergency use authorization (EUA) by the FDA, in combination with tixagevimab, for the pre-exposure prophylaxis of COVID-19 in adult and pediatric patients aged 12 years and older weighing at least 40 kg. Furthermore, patients must not be currently infected with SARS-CoV-2 or have had known exposure to an individual infected with SARS-CoV-2 and must either be immunocompromised due to a medical condition, medication, or treatment or be otherwise ineligible for vaccination with any eligible COVID-19 vaccine due to a history of severe adverse reactions.

In the US, the combination of cilgavimab and tixagevimab is not authorized for the treatment or post-exposure prophylaxis of COVID-19 and is not a substitute for COVID-19 vaccination. Individuals receiving therapy following COVID-19 vaccination should wait at least two weeks.

In Europe and Canada, cilgavimab in combination with tixagevimab is an approved pre-exposure prophylaxis therapy for COVID-19 in adults and adolescents aged 12 years and older weighing at least 40 kg.