Promising outcomes from the REGEN-COV part II research

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which is responsible for Coronavirus Disease 2019 (COVID-19), has reached almost every country in the world, causing over five million deaths. The rapid rate of transmission of SARS-CoV-2 has led many countries to adopt restrictive and costly social distancing measures, including mandatory face masks, locking down public spaces, and even locking / staying at home.

While some developed countries have launched mass vaccination campaigns that have allowed most of these restrictions to be lifted, many developing countries cannot provide the logistics or resources for the extensive cold chains necessary for adequate vaccine storage. In addition, worrying SARS-CoV-2 variants (VOCs) continue to develop, many of which show increased transmission and infectivity, as well as the ability to evade both vaccine-induced and natural immunity.

Study: Phase 2 dose range study on the virological efficacy and safety of the combination of COVID-19 antibodies casirivimab and imdevimab in the outpatient setting. Image source: SmartPhotoLab / Shutterstock.com

About the study

With the need for COVID-19 treatments remaining high, researchers at Regeneron Pharmaceuticals have tested a new promising drug. Treatment with REGEN-COV is based on two antibodies, including casirivimab and imdevimab, given in a single 1: 1 dose given intravenously (IV) or subcutaneously (sc). The first results of their phase II study are presented in their current study, which was published on the preprint server medRxiv *.

The researchers used a randomized, double-blind study with parallel control groups that received placebos. The study looked at a range of doses.

Nasopharyngeal (NP) smears and blood cells were collected every other day for the first week and then monthly for the next four months. All study participants were over 18 years old and had received a positive SARS-CoV-2 test result 72 hours prior to randomization. No patients were included in the study who were thought to be at a more severe risk of COVID-19.

Patients who were not eligible for the control group received a single dose of REGEN-COV administered either iv or sc. IV doses ranged from 300 to 2,400 milligrams (mg), while SC doses were only given at 600 or 1,200 mg.

While health professionals, care providers, and patients were blinded to control group and dose, it was not possible to blind them to method of administration. The researchers primarily looked at the change in baseline viral load in NP samples over the first seven days. In particular, the researchers also looked at the number of undesirable and serious side effects.

A total of 815 patients were included in the study. An ANCOVA model was fitted to the data for statistical analysis, using treatment group as a fixed effect and baseline viral load and treatment as covariates.

Study results

Of the total of 815 patients, 523 were assigned to IV treatment and 292 to SC treatment. No serious cases of COVID-19 occurred during the study. About 90% of the patients were symptomatic at low risk and the rest were asymptomatic.

The researchers found that both IV and SC-administered doses of REGEN-COV significantly reduced viral load by day seven. The most effective reduction in viral load was observed when 2,400 mg was administered iv.

At 1,200 mg sc and iv reduced the viral load equally, and the administered dose when administered sc had no effect on the decrease in viral load. The IV dose tended to lead to a steady decrease in the antibody concentration over every seven days, while the sc dose led to a near maximum value of the REGEN-COV concentration up to the third day3, although it continued to increase slowly up to the seventh day.

There were no serious safety concerns, although one patient had a slight reaction. It was found that two other safety issues were unrelated to the drug.

Conclusions

The authors highlight how the drug demonstrated significant reductions in viral load and rapid uptake of REGEN-COV by the body at all dosages after both route administration. The lack of safety issues combined with linear and proportional pharmacokinetics suggest the drug is safe for further testing in patients with more severe COVID-19 and in those at risk of progression to a more severe prognosis.

While higher doses resulted in increased reductions in viral load, the researchers point out that even the lowest dose showed antibody levels reaching between 60 and several hundred times that required to neutralize most VOCs, suggesting that smaller doses might be worth investigating.

As many VOCs begin to show an increased ability to evade both vaccine-induced and natural immunity, the increasing amount of promising drugs nearing availability will be a relief for public health policymakers and healthcare workers. In addition, the availability of these antiviral drugs should enable more informed decisions about patient care and the need to reintroduce restrictions.

*Important NOTE

medRxiv publishes preliminary scientific reports that have not been peer reviewed and therefore should not be considered conclusive, that guide clinical practice / health-related behavior or should be treated as established information