FDA EUA for COVID-19 pre-exposure prophylaxis with long-acting monoclonals is a key proof of concept

On Dec. 8, FDA granted an emergency use authorization for “New Long-Acting Monoclonal Antibodies for Pre-exposure Prevention of COVID-19 in Certain Individuals.” It has not been reported if this combination of two monoclonals is active against the Omicron variant.

Although the EUA was limited to specific populations (which are described below) unable or unlikely to benefit from the available COVID-19 vaccines, the proof of concept that one-time administration of monoclonals can provide up to 6 months of pre-exposure prophylaxis has multiple potential applications for COVID, e.g., for health providers across the spectrum outside and inside hospitals and laboratories. The innovation that allowed extension of this one-dose combination monoclonal antibody protection to ~ 6 months could offer breakthroughs for multiple other infectious diseases beyond COVID.

The Dec. 8 press release stated: “Today, the U.S. Food and Drug Administration issued an emergency use authorization (EUA) for AstraZeneca’s Evusheld (tixagevimab co-packaged with cilgavimab and administered together) for the pre-exposure prophylaxis (prevention) of COVID-19 in certain adults and pediatric individuals (12 years of age and older weighing at least 40 kilograms [about 88 pounds]). 

The product is only authorized for those individuals who are not currently infected with the SARS-CoV-2 virus 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 (examples of such medical conditions or treatments can be found in the fact sheet for health care providers) or;
• a history of severe adverse reactions to a COVID-19 vaccine and/or component(s) of those vaccines, therefore vaccination with an available COVID-19 vaccine, according to the approved or authorized schedule, is not recommended.”

On Dec. 10, 2021, FDA announced that it was reissuing its Dec. 8 EVUSHELD EUA letter of authorization “in its entirety, to add a new limitation detailing the scope of healthcare providers who are authorized to prescribe EVUSHELD for use under this EUA. An additional condition requiring AstraZeneca to genotype and phenotype virus isolated from prophylaxis failures has also been added.”

For clinicians, a good source of data on safety and efficacy used to support the EUA appears in the 23-page “Fact Sheet for Health Care Providers.” Table 6 provides the “Incidence of Symptomatic COVID-19 in Adults (PROVENT).” The 77% “reduced risk of infections with SARS-CoV-2 and developing COVID” was derived from the 1.0% infection of 1,731 people in the placebo group versus the 0.2% infection of 3,441 people receiving the combination monoclonals tixagevimab and cilgavimab (“EVUSHELD”).

This monoclonal combination from AstraZeneca is not authorized for post-exposure prophylaxis (see the above Fact Sheet under results of the STORM CHASER study).

In contrast, the Regeneron monoclonal combination that received an EUA from FDA in August 2021 was only for post-exposure prophylaxis and explicitly not for pre-exposure prophylaxis.