A single injected administration of Regeneron's monoclonal antibody cocktail cuts the risk of developing COVID-19 by over 80%, reports MedicalBrief. Antibody drugs may give doctors a new way to protect high-risk people who havenʼt been inoculated or who may not respond well to vaccination.
The Regeneron study enrolled 1,500 healthy volunteers, each of whom shared a home with someone who tested positive for SARS-CoV-2, and randomised them to receive a single dose of its antibody treatment, given subcutaneously as four shots, or placebo. After 29 days, 11 patients in the treatment group developed COVID-19 compared to 59 on placebo. And for the subjects who got COVID-19 despite treatment, their symptoms resolved after one week, compared to three weeks for those on placebo. In 204 patients who had already tested positive for the SARS-CoV-2 virus at the study’s outset, the injection reduced their chances of progressing to symptomatic COVID-19 by 31%.
The results were made public in a press release and will be published in a scientific journal or presented at a medical meeting at a later date.
Stat News reports that those results mirror similar results seen in a study conducted by Eli Lilly of its monoclonal antibody in nursing homes. One key difference: While in previous studies by both Lilly and Regeneron, antibodies had to be given intravenously, in this one Regeneron used a formulation that could be given with an under-the-skin injection. Lilly is also exploring a subcutaneous injection of its antibodies.
That’s “a really, really big deal,” said Myron Cohen, director of the Institute for Global Health and Infectious Diseases at the University of North Carolina and one of the study’s lead investigators. He said that having to start an IV is “unequivocally” one of the barriers to using the antibodies either for treatment or prevention. The other barrier? Awareness.
Regarding why do we need antibodies when there are already vaccines, Stat News quotes Dan Barouch, the director of the Centre for Virology and Vaccine Research at Beth Israel Deaconess Medical Centre and a key figure in the development of the J&J vaccine and another investigator in Regeneron’s study as saying that the approaches are “complementary.”
“As of now, there are still substantial numbers of people who are not fully vaccinated,” Barouch said. What’s more, some people, including those with compromised immune systems, might not generate enough antibodies one their own – and could benefit from antibodies that are injected into their bodies.
The New York Times reports that the findings are the latest evidence that such lab-made drugs not only prevent the worst outcomes of the disease when given early enough, but also help prevent people from getting sick in the first place.
The report says using the cumbersome drugs preventively on a large scale wonʼt be necessary: Vaccines are sufficient for the vast majority of people and are increasingly available. Still, antibody drugs like Regeneronʼs could give doctors a new way to protect high-risk people who havenʼt been inoculated or who may not respond well to vaccination, such as those taking drugs that weaken their immune system. That could be an important tool as rising coronavirus cases and dangerous virus variants threaten to outpace vaccinations.
Thereʼs “a very substantial number of people” in the US and globally who could be a good fit to receive these drugs for preventive purposes, said Cohen, who leads monoclonal antibody efforts for the COVID Prevention Network, a National Institutes of Health (NIH)-sponsored initiative that helped to oversee the trial. “Not everyone is going to take a vaccine, no matter what we do, and not everyone is going to respond to a vaccine,” Cohen is quoted in the NYT as saying.
Dr Rajesh Gandhi, an infectious diseases physician at Massachusetts General Hospital who was an investigator for the study, said the data were “promising” for people who have not yet been vaccinated. Even so, he said, the study did not enrol the type of patients that would be needed to assess whether the drug should be used preventively for immunocompromised patients. “I would say we donʼt yet know that,” Gandhi said.
The NYT reports that the treatment received emergency authorisation in November. Doctors are using it, as well as another antibody cocktail from Eli Lilly, for high-risk COVID patients. But use of the antibody drugs has been slowed not by a shortage of doses, but by other challenges, though access has improved in recent months. Many patients donʼt know to ask for the drugs or where to find them.
Also, the NYT reports, many hospitals and clinics have not made the treatments a priority because they have been time-consuming and difficult to administer, in large part because they must be given via intravenous infusion.
Regeneron plans to ask the FDA to allow its drug to be given via an injection, which would allow it to be given more quickly and easily.
Regeneron Pharmaceuticals announced positive data from a Phase 3 trial (2069B) of recently infected asymptomatic COVID-19 patients, evaluating REGEN-COV™ (casirivimab with imdevimab) 1,200 mg administered via subcutaneous (SC) administration. REGEN-COV reduced the overall risk of progressing to symptomatic COVID-19 by 31% (primary endpoint), and by 76% after the third day. The trial also demonstrated that REGEN-COV shortened symptom duration and markedly reduced viral levels.
The Phase 3 trial is the second to report results, which was jointly run with the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH. The trial enrolled 204 individuals without any COVID-19 symptoms who tested positive for SARS-CoV-2 but did not have anti-virus antibodies at baseline and were randomised to receive either 1 dose of REGEN-COV (1,200 mg) or placebo.
"COVID-19 transmission often occurs via infected people who do not yet have symptoms, so it is critical that we rapidly diagnose and treat these individuals for their own health and to prevent transmission," said Dr Katharine Bar, co-principal investigator of the trial and assistant professor of medicine, infectious diseases, Hospital of the University of Pennsylvania. "These data pave the way for REGEN-COV to be used before patients become symptomatic, with a more convenient subcutaneous administration."
The trial met all primary and key secondary endpoints. In addition to reducing the risk of symptomatic infections, the total number of weeks patients experienced symptoms was nearly cut in half (45%) with REGEN-COV, and the viral burden was reduced by more than 90%. While not included in the initial analysis plan, researchers also found that 0 REGEN-COV patients and 6 placebo patients were either hospitalised or visited the emergency room because of COVID-19 during the 29-day efficacy assessment period.
The data build on previously announced results from the Phase 3 outcomes (2067) and Phase 2 virology (20145) trials in non-hospitalised COVID-19 patients. The Phase 3 outcomes trial in high-risk symptomatic outpatients showed that REGEN-COV (2,400 mg and 1,200 mg administered intravenously [IV]) reduced hospitalisation or death by 70%. The Phase 2 virology trial in low-risk outpatients showed that all REGEN-COV doses studied had similar efficacy in rapidly reducing viral load (IV: 2,400 mg, 1,200 mg, 600 mg and 300 mg; SC: 1,200 mg and 600 mg).
"These Phase 3 data provide even more evidence that REGEN-COV, this time given to asymptomatic patients via convenient injections, can change the course of COVID-19 infection in non-hospitalized patients," said Dr George D Yancopoulos, president and chief scientific officer at Regeneron. "In this trial, the REGEN-COV antibody cocktail effectively prevented asymptomatic patients from becoming symptomatic, and rapidly lowered their viral load."
Adverse events (AEs) occurred in 34% (n=52 out of 155) of REGEN-COV patients and 48% (n=75 out of 156) of placebo patients, and serious AEs occurred in 0% (n=0) of REGEN-COV and 3% (n=4) of placebo patients. Injection site reactions, all of which were grades 1-2, occurred in 4% (n=6) of REGEN-COV and 1% (n=1) of placebo patients. No patients from either group withdrew from the trial due to AEs, and there were no deaths.
REGEN-COV continues to be evaluated in clinical trials in multiple settings for COVID-19: for the prevention of COVID-19 in household contacts of infected individuals, and in non-hospitalised and certain hospitalised patients, including the open-label RECOVERY trial of hospitalised patients in the UK. As of April 2021, more than 25,000 people have participated in clinical trials involving REGEN-COV.
Full Stat News report (Open access)