Regeneron Pharmaceuticals Inc. posted positive initial results from its ongoing phase III study of its monoclonal antibody cocktail, REGEN-COV (casirivimab and imdevimab), used as a passive vaccine, designed to provide immediate short-term passive immunity to prevent COVID-19 in people at high risk of infection due to household exposure to a COVID-19 patient. Eli Lilly and Co. reported upbeat news the same day, as the phase III Blaze-1 trial testing its antibody cocktail met its primary and key secondary endpoints.
In Regeneron’s study, the new data showed 100% prevention of symptomatic infection and roughly 50% lower overall rates of symptomatic and asymptomatic infection.
In passive vaccination “protection is immediate but only lasts as long as the antibodies do in the body,” Regeneron spokeswoman Alexandra Bowie told BioWorld. “We expect this to be at least a month based on the half-life of our COVID antibodies in particular.”
Bowie added that the passive vaccine could be administered as an injection at a doctor’s office or clinic as an immediate protection against infection once an index patient, someone with the first known case in a family, is diagnosed.
The lower number of infections occurring with REGEN-COV therapy were all asymptomatic, with decreased peak virus levels and short duration of viral shedding, the company added. Infections in the REGEN-COV group lasted no more than one week. About 40% of infections in the placebo group lasted three to four weeks.
The cocktail treatment also found a lower disease burden as there were fewer viral shedding weeks (nine weeks for REGEN-COV compared to 44 weeks with placebo) and fewer total high viral shedding weeks.
The data come from an exploratory analysis on the first 400 evaluable people enrolled in the trial. Those patients receiving REGEN-COV got a 1,200-mg dose via I.V.
“We expect prophylactic antibody use will be an important tool in the fight against COVID for individuals at high risk of infection, or after exposure, supplementing vaccine rollouts and social distancing measures,” wrote SVB Leerink Geoffrey Porges on Jan. 26, “and if efficacy and safety are ultimately comparable, we expect REGEN-COV to see better uptake than [Eli Lilly and Co.’s] bamlanivimab given the more convenient administration.”
Bamlanivimab and etesevimab
In Lilly’s Blaze-1 trial, the company’s bamlanivimab and etesevimab cocktail decreased the risk of hospitalizations or death by 70%. Bamlanivimab is a recombinant, neutralizing human IgG1 monoclonal antibody, while etesevimab is a recombinant fully human monoclonal neutralizing antibody, which specifically binds to the SARS-CoV-2 surface spike protein receptor binding domain with high affinity and can block the virus from binding to an ACE2 host cell surface receptor..
The phase III study primary endpoint was reducing COVID-19-related hospitalizations and deaths in high-risk patients who had recently been diagnosed with COVID-19.
The study also produced improvement on key secondary endpoints, including the change from baseline to day seven in SARS-CoV-2 viral load, persistently high SARS-CoV2 viral load on day seven, time to sustained symptom resolution, and COVID-related hospitalization, emergency room visit or death from any cause from baseline by day 29.
There were 10 deaths, all of them patients taking placebo. There were no deaths for patients taking the cocktail.
In a Jan. 26 conference call with investors, Daniel Skovronsky, senior vice president, chief scientific officer and president of Lilly Research Labs, pondered how quickly the company could launch and scale the treatment.
“So we don't know how fast we can scale,” he said. “I think last time we did it, we started in March. And by October, we had that phase II data, and we're ready to scale. I think we have the potential to go even faster in the future. So we're talking months to reach that stage. Of course, manufacturing scales from there. And that's why we need to start working on variants as quickly as possible so that manufacturing can be scaled before they're too widespread.”
The Blaze-1 study closely followed Lilly’s Jan. 21 release of positive data for bamlanivimab in its phase III Blaze-2 study, which reduced nursing home residents’ risk of contracting symptomatic COVID-19 by 80%.