Regeneron’s Antibody Cocktail Shows Promise as ‘Passive Vaccine’ Against COVID-19
Regeneron Pharmaceuticals reported initial results from a phase 3 study showing that, compared to placebo, its antibody cocktail REGEN-COV (casirivimab/imdevimab) reduced overall COVID-19 infections seen within the first week among people at high risk of contracting SARS-CoV-2, with 100% prevention of symptomatic cases. Chief scientific officer George Yancopoulos said the findings suggest REGEN-COV may confer “immediate passive immunity to those at high risk of infection, in contrast to active vaccines which take weeks to provide protection,” adding it could also be an important option for immunocompromised people or those who are otherwise unable to be vaccinated.
The ongoing prevention trial has enrolled over 2000 people aged 43 years on average, and roughly split between men and women. They were eligible to participate in the study if they had a household member with COVID-19. The study, whose full results are expected to be released early in the second quarter, is evaluating the ability of REGEN-COV to prevent asymptomatic and symptomatic COVID-19 infections as the primary endpoint.
The current analysis focused on 409 evaluable subjects who were seronegative for COVID-19 at baseline and were tested weekly by nasopharyngeal swab. Regeneron said that among the 186 people given REGEN-COV, none had symptomatic infection, compared with eight cases seen in the placebo group, which enrolled 223 individuals. Passive vaccination with REGEN-COV also led to roughly 50% lower overall rates of infection, including both symptomatic and asymptomatic cases, with 10 cases in the REGEN-COV arm and 23 for placebo.
Lower disease burden
Regeneron noted that infections occurring with REGEN-COV therapy, which were all asymptomatic, had decreased peak virus levels versus the placebo group, where there was a more than 100-fold higher peak viral load. Moreover, no infected individuals in the REGEN-COV group had “high” viral loads, defined as exceeding 104 copies/mL, whereas 62% of infected individuals in the placebo group did. The company also said infections in the REGEN-COV arm lasted no more than 1 week, while approximately 40% of infections among placebo group participants lasted 3 to 4 weeks.
In terms of disease burden, Regeneron stated that total viral shedding weeks in the REGEN-COV group was 9 weeks, compared to 44 weeks for placebo, including a total 22 weeks of “high” viral shedding. The placebo group also had a total of 18 symptomatic weeks, compared to none for REGEN-COV. Meanwhile, adverse events were more frequent for those on placebo at 18%, versus 12% for REGEN-COV, driven by the increased rate of SARS-CoV-2 infections. In addition, there was one death and one COVID-19-related hospitalization in the placebo group, versus none for the treatment arm.
Injection instead of infusion
David Weinreich, who heads global clinical development at Regeneron, noted that “in this prevention trial, REGEN-COV was given as injections rather than an infusion, which makes administration much more convenient and efficient.” US officials recently said the bulk of COVID-19 antibody treatments delivered to states every week were going unused in part because they have to be administered by infusion in a hospital or outpatient setting, and within a small window after patients contract the virus. Meanwhile, Weinreich said Regeneron plans to discuss the latest results with regulatory authorities, including the potential to expand its existing emergency-use authorization.
The dual antibody therapy was authorized by the FDA for emergency use last November to treat mild-to-moderate COVID-19 in adults and paediatric patients. Regeneron previously said REGEN-COV reduced viral load and lowered patient medical visits, according to a phase 2/3 study analysis of COVID-19 outpatients. The treatment is also being studied in two late-stage studies involving hospitalized patients, while the company is investigating whether the therapy can prevent SARS-CoV-2 infection when delivered intranasally via adeno-associated virus vectors.
Separately on Tuesday, Eli Lilly reported phase 3 study results showing that the antibody combination of bamlanivimab plus etesevimab significantly reduced COVID-19-related hospitalizations and deaths by 70% in high-risk patients recently diagnosed with SARS-CoV-2.