Despite increasing vaccinations, the need for COVID-19 treatments has not gone away, particularly in light of vaccine shortages and rising case numbers in some countries around the world. This is why Regeneron’s announcement of positive clinical trial results that show its antibody cocktail treatment can cut deaths among hospitalized patients is welcome news. It is the first trial to demonstrate that any antibody treatment could improve survival in patients hospitalized with COVID-19.
The results come from the UK RECOVERY trial, which is the largest study evaluating a monoclonal antibody treatment in patients hospitalized with severe COVID-19.
Regeneron Pharmaceuticals Inc.’s (NASDAQ: REGN) antibody therapy REGEN-COV consists of a cocktail of two virus-neutralizing monoclonal antibodies, casirivimab and imdevimab, which bind non-competitively to the receptor binding domain (RBD) of the spike protein of SARS-CoV-2. This helps reduce the potential of mutant viruses to evade treatment and protects against spike variants.
The RECOVERY trial found that adding REGEN-COV to standard care reduced the risk of death by 20 percent in patients who had not elicited a natural antibody response on their own against SARS-CoV-2, compared with standard care alone.
REGEN-COV received emergency use authorization (EUA) from the US Food and Drug Administration (FDA) in November of last year for the treatment of treat mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older) with positive results of direct SARS-CoV-2 viral testing and who are at high risk for progression to severe COVID-19.
Regeneron has enlisted the help of Roche to help manufacture the antibody drug.
The primary outcome of RECOVERY demonstrated that adding 8,000 mg of REGEN-COV to standard care reduced all-cause mortality by 20 percent in seronegative patients compared to standard care alone (24 percent of patients in the REGEN-COV group died versus 30 percent in the usual care group by day 28, yielding a rate ratio of 80 percent).
This translates into six fewer deaths for every 100 seronegative patients treated with the therapy, researchers part of the RECOVERY trial said, according to Reuters.
There was no significant difference in mortality between the two groups when seropositive cases (those that had mounted an immune response and produced antibodies against the virus), as well as cases with unknown status, were added to the analysis. This means the drug is particularly beneficial for those hospitalized patients that fail to generate an immune response against SARS-CoV-2.
Several analyses, including a recent publication in Cell, have shown that REGEN-COV retains potency against the main variants of concern (VoC) circulating in the US, including P.1 (first identified in Brazil, now classified by the World Health Organization [WHO] as Gamma), B.1.351 (first identified in South Africa, now classified by the WHO as Beta) and B.1.162.2 (first identified in India, now classified by the WHO as Delta).
The combined frequency of the P.1 and B.1.351 variants is now upwards of ten percent of new COVID-19 diagnoses across eight states (Arizona, California, Florida, Illinois, Indiana, Massachusetts, Oregon and Washington). The prevalence of these and other variants continues to be closely monitored.
The RECOVERY trial also demonstrated that the steroid dexamethasone and Roche’s arthritis drug Actemra (tocilizumab) could cut deaths in hospitalized patients.
COVID-19 Monoclonal Antibodies: Treatment Versus Prevention
Monoclonal antibody treatments for COVID-19 developed by other makers include Eli Lilly’s dual antibody cocktail of bamlanivimab and etesevimab. However, as a monotherapy, bamlanivimab had its EUA revoked by the FDA in April in light of an increased risk of treatment failure due to the steady increase of SARS-CoV-2 viral variants resistant to bamlanivimab alone.
And while the bamlanivimab and etesevimab combination has been shown to decrease the risk of hospitalization, it does little for already hospitalized patients, making REGEN-COV the first to do so.
In addition to its viral vector-based COVID-19 vaccine, AstraZeneca has also been developing its own monoclonal antibody treatment (AZD7442) against the infection. In fact, it also released data from its ongoing trial of the drug this week, coinciding with Regeneron’s announcement. However, in contrast to Regeneron’s positive results, AstraZeneca revealed that a late-stage trial failed to offer evidence that its COVID-19 antibody therapy could protect against symptomatic disease. Despite this, the company says they are encouraged by the protection observed in PCR negative participants.
On the other hand, Regeneron’s REGEN-COV demonstrated its ability to prevent symptomatic illness among people who come in contact with a COVID-19 infected individual in a Phase III prevention trial. As such, the company is seeking an EUA for the drug as a preventative treatment.