FDA Issues Emergency Use Authorization for Long-Acting Antibody Combination, First Pre-Exposure Prophylaxis for COVID-19

Studies are currently underway to determine the impact of the Omicron COVID-19 variant on the long-acting antibody combination.

Officials with the FDA have approved an emergency use authorization (EUA) for tixagevimab co-packaged with cilgavimab (Evusheld; AstraZeneca) as the first antibody therapy for pre-exposure prophylaxis of COVID-19. First doses will be available soon, according to a press release.

The EUA was granted for adults and adolescents 12 years of age and older who weigh 40 kg or more who are moderately to severely immunocompromised due to a medical condition or immunosuppressive medications, and who therefore may not mount an adequate immune response to vaccination. It is also approved in those for whom COVID-19 vaccination is not recommended. Recipients of the long-acting antibody combination should not be currently infected with COVID-19 or had recent known exposure to a person infected with SARS-CoV-2.

“Millions of people in the US and around the world remain at serious risk for COVID-19 because their immune systems do not generate a sufficient immune response, even after receiving all recommended doses of vaccine,” said Myron J. Levin, MD, principal investigator of the PROVENT trial, in the press release. “I am excited to offer my patients Evusheld as an easily-administered new option that provides long-lasting protection that could help them return to their everyday lives.”

Approximately 2% of the global population are considered to be at an increased risk of an inadequate response to COVID-19 vaccination and approximately 7 million people in the United States could benefit from the antibody combination. This includes patients with blood cancers or other cancers being treated with chemotherapy, and those taking medications after an organ transplant or who are taking immunosuppressive drugs for other conditions. The long-acting antibody combination is delivered as an intramuscular dose.

Primary data supporting the EUA are from the ongoing PROVENT phase 3 pre-exposure prevention trial, which found a statistically significant reduction in the risk of developing symptomatic COVID-19 compared to placebo. At the primary analysis, researchers found a 77% reduction and at median 6-month analysis they found an 83% reduction. Protection from the virus continued for at least 6 months. More follow-up is needed to establish the full duration of protection, according to the press release.

“One of the primary questions I keep getting asked by patients is ‘When can I hug my grandchildren again?’” said Brian Koffman, MDCM, MS Ed, co-founder, executive vice president, and chief medical officer of the Chronic Lymphocytic Leukemia Society, in the press release. “As a physician and person with a weakened immune system, I am filled with hope now that Evusheld will soon be available to those who can’t count on vaccination alone to provide the protection they need.”

Studies are currently underway to determine the impact of the Omicron variant on Evusheld. Of the variant’s binding site substitutions relevant to Evusheld that have been tested to date in preclinical assays, none have been associated with avoiding neutralization, according to the press release. In vitro findings have demonstrated that Evusheld neutralizes other recently emerged variants, including the Delta and Mu variants.

“Evusheld neutralizes all previous SARS-CoV-2 variants to date, and we are working quickly to establish its efficacy against the new Omicron variant,” said Mene Pangalos, PhD, executive vice president of biopharmaceuticals research and development at AstraZeneca, in the press release.

AstraZeneca has agreed to provide the US government with 700,000 doses of Evusheld, which the government plans to distribute at no cost and on a pro rata basis. AstraZeneca is also proceeding with filing around the world for potential emergency use authorization or conditional approval of Evusheld for both COVID-19 prophylaxis and treatment.

“We are proud to play a leading role in fighting the COVID-19 pandemic and, with Evusheld, we now have the first antibody therapy authorized in the US to prevent COVID-19 symptoms before virus exposure, while also providing long lasting protection with a single dose,” Pangalos said in the press release.

REFERENCE

Evusheld (formerly AZD7442) long-acting antibody combination authorized for emergency use in the US for pre-exposure prophylaxis (prevention) of COVID-19. News release. AstraZeneca; December 8, 2021. Accessed December 9, 2021. https://www.astrazeneca.com/media-centre/press-releases/2021/evusheld-long-acting-antibody-combination-authorised-for-emergency-use-in-the-us-for-pre-exposure-prophylaxis-prevention-of-covid-19.html