Regeneron Pharmaceuticals has announced a dual win for its single-dose monoclonal antibody cocktail as Phase IIIa/b trials found the injection effective in both preventing Covid-19 infections and halting the disease’s progression in asymptomatic patients.
REGEN-COV (casirivimab with imdevimab) is a cocktail of two monoclonal antibodies designed to block infectivity of the Covid-19 causing virus, SARS-CoV-2.
Both the IIIa prevention trial and the IIIb treatment trial testing REGEN-COV were jointly run with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).
To qualify for the multi-part Phase III trial, all participants were enrolled without any Covid-19 symptoms and lived in the same household as an individual who tested positive for SARS-CoV-2 within the previous four days. All participants were tested using nasal swabs and those who tested negative joined the prevention trial (2069A), while those who tested positive joined the treatment trial (2069B).
The double-blind, placebo-controlled Phase IIIa prevention trial (2069A) enrolled 1,505 uninfected people, and met its primary and key secondary endpoints proving that REGEN-COV 1,200 mg administered subcutaneously decreased the risk of symptomatic infections by 81% in people who were not infected when they started the trial.
The drug’s efficacy was demonstrated quickly after the injection, with the risk reduction of symptomatic Covid-19 amounting to 72% in the first week. The reduction in subsequent weeks was 93%.
“These data suggest that REGEN-COV can complement widespread vaccination strategies, particularly for those at high risk of infection. Importantly, to date REGEN-COV has been shown in vitro to retain its potency against emerging COVID-19 variants of concern,” said Dr Myron Cohen, who leads monoclonal antibody efforts at the NIH-sponsored COVID Prevention Network (CoVPN) and is director of the Institute for Global Health & Infectious Diseases at the University of North Carolina at Chapel Hill.
“Despite standard precautions to reduce transmission, nearly 10% of unvaccinated individuals living with an infected person developed symptomatic infections if they did not receive REGEN-COV. If authorised, convenient subcutaneous administration of REGEN-COV could help control outbreaks in high-risk settings where individuals have not yet been vaccinated, including individual households and group living settings.”
The case for an antibody therapy as an alternative prevention method alongside the many vaccines now being rolled out is that it can offer readily available immune protection as, for a vaccine to work, recipients need to have a strong enough immune system to produce coronavirus-fighting antibodies by themselves, a process that takes time.
“These findings are very encouraging and suggest that REGEN-COV is highly effective at preventing symptomatic Covid-19 in household contacts of SARS-CoV-2 infected individuals,” said Harvard Medical School Professor of Medicine Dan H. Barouch, co-principal investigator of the trial and director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center.
“The rapid and robust protection, together with the subcutaneous route of administration, support the practical utility of these antibodies in protecting against Covid-19 in multiple settings, including after high-risk exposures. These antibodies may be particularly useful in individuals who are not yet vaccinated, and may also have potential in those who are immunosuppressed and may not respond well to vaccines.”
The Phase IIIb treatment trial (2069B) enrolled 204 individuals without any Covid-19 symptoms who tested positive but did not have anti-virus antibodies at baseline, and were randomised to receive either one dose of REGEN-COV (1,200 mg) or placebo.
This trial also met all primary and key secondary endpoints. 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 showed that REGEN-COV reduced symptom duration and markedly decreased viral load levels.
The total number of weeks patients experienced symptoms was nearly slashed in half (45%), and the viral load was reduced by more than 90%.
Researchers found that zero REGEN-COV patients and six placebo patients were either hospitalised or visited the emergency room because of Covid-19 during the 29-day efficacy assessment period.
“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 co-principal investigator of the trial and Assistant Professor of Medicine, Infectious Diseases, Hospital of the University of Pennsylvania, Katharine Bar. “These data pave the way for REGEN-COV to be used before patients become symptomatic, with a more convenient subcutaneous administration.”
Regeneron president and chief scientific officer George D. Yancopoulos said: “These Phase III 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-hospitalised patients. In this trial, the REGEN-COV antibody cocktail effectively prevented asymptomatic patients from becoming symptomatic, and rapidly lowered their viral load.”
The treatment and prevention trials both enrolled over 30% of patients that had at least one known factor that put them at high risk of suffering severe consequences from Covid-19.
Among participants enrolled in the prevention trial, 41% were Latino/Hispanic and 9% were Black/African American. 33% were obese and 38% were in their 50s.
Of participants enrolled in the treatment trial, 35% were Latino/Hispanic and 5% were Black/African American. 32% were obese and 34% were in their 50s.
Regeneron’s antibody cocktail is already authorised to stop disease progression in sick patients, but this new data shows that a lower dose can prevent Covid-19 altogether in healthy people, and prevent progression in asymptomatic cases of infection.
The firm plans to present the data to the US Food and Drug Administration and request an extended emergency use authorisation for REGEN-COV as a preventative measure against Covid-19.
Regeneron is working in partnership with Swiss pharma giant Roche to boost global supplies of REGEN-COV, with Roche taking the lead on development and distribution of the antibody cocktail outside of the US.