Regeneron to Investigate Delivery of COVID-19 Antibody Cocktail via Gene Therapy Platform

Regeneron Pharmaceuticals, Inc. (Tarrytown, NY, USA) and the University of Pennsylvania (Philadelphia, PA, USA) have entered into a collaboration to investigate the delivery of COVID-19 antibody cocktail via the gene therapy platform.

The research collaboration will investigate whether Regeneron’s casirivimab and imdevimab investigational antibody cocktail can prevent COVID-19 infection when delivered intranasally via Adeno-Associated Virus (AAV) vectors. Regeneron’s antibody cocktail (casirivimab and imdevimab administered together) is being studied in clinical trials for the treatment and prevention of COVID-19 and was recently granted an Emergency Use Authorization by the US Food and Drug Administration (FDA) in certain high-risk patients with mild to moderate COVID-19.


Gene therapy pioneer James Wilson, MD, PhD, professor of Medicine and director of the Gene Therapy Program and the Orphan Disease Center at Penn’s Perelman School of Medicine, and his team will work with Regeneron to study the safety and effectiveness of using AAV vectors to introduce the sequence of the cocktail’s virus-neutralizing antibodies directly to nasal epithelial cells. This new collaboration will introduce the application of AAVs, which have traditionally been used for gene therapies against deadly genetic diseases, to the fight against the novel coronavirus.

To date, AAV has been shown to be a particularly durable method of introducing antibodies into the body, because the AAV genome that codes for the therapeutic antibody remains stable in the nucleus of transduced cells. In clinical trials thus far, casirivimab and imdevimab are delivered together by intravenous or subcutaneous injection, with data showing antibody levels lasting a month or more. Based on data from Regeneron’s preclinical studies showing that the antibody cocktail can prevent infection in animal models, Wilson’s team is hopeful that introducing the therapy via single dose of AAV will be able to produce similar protection for potentially a longer duration.

The collaboration between Wilson and Penn’s GTP and Regeneron will have two phases. The first phase will include the validation of the effectiveness of the antibodies delivered via AAV in a large animal model challenge study, where animals will be given the antibody cocktail via AAV and exposed to the novel coronavirus. If that study is successful, the research team will complete studies to support filing of an investigational new drug (IND) application with the FDA, which is a necessary step before clinical trials in humans can begin.

“Early clinical data from Regeneron show that their investigational antibody combination may play a role in helping treat the disease and reduce severity in those who are infected. We hope to leverage the virus-neutralizing ability of this antibody cocktail for prevention of COVID-19 using a novel delivery mechanism, as well,” said Wilson. “The advantage of AAV in this application is that can achieve sustained expression of the antibodies in the nasal mucosa, which is the site of infection, following a single administration. In contrast to traditional vaccines, AAV delivery of antibodies provides a rapid onset of response and no reliance on the need for the recipient to mount an immune system response over time. This latter feature may be particularly attractive in people with weakened immune systems, like the elderly, or people who need rapid protection, like frontline healthcare workers.”

“Regeneron scientists specifically selected casirivimab and imdevimab to block infectivity of SARS-CoV-2, the virus that causes COVID-19, and we have been encouraged by the promising clinical data thus far,” said Christos Kyratsous, PhD, Vice President of Research, Infectious Diseases and Viral Vector Technologies at Regeneron. “In the quest to use cutting-edge science to help end this disruptive and often very devastating disease, we are excited to explore alternate delivery mechanisms such as AAV that may extend the potential benefits of this investigational therapy to even more people around the world.”

Related Links:
Regeneron Pharmaceuticals, Inc.
University of Pennsylvania