Promising results of the REGEN-COV Phase II study

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which is the virus responsible for 2019 coronavirus disease (COVID-19), has reached almost every country in the world and has killed more than five million people . The rapid rate of transmission of SARS-CoV-2 has led many countries to adopt restrictive and costly social distancing measures, including mandatory masks, closures of public spaces, and even lockdown / stay-at-home orders.

While some developed countries have launched mass vaccination campaigns that have lifted most of these restrictions, many developing countries cannot provide the logistics or the resources for the extensive cold chains needed for adequate storage of foodstuffs. vaccines. In addition, the development of serious variants of SARS-CoV-2 (VOC) continues to occur, many of which exhibit increased transmission and infectivity, as well as the ability to evade both vaccine-induced immunity. and natural immunity.

To study: Phase 2 assay study of virological efficacy and safety of the COVID-19 antibody combination casirivimab and imdevimab on an outpatient basis. Image Credit: SmartPhotoLab / Shutterstock.com

About the study

Since the need for COVID-19 treatments remains high, researchers at Regeneron Pharmaceuticals have tested a new drug that shows promise. REGEN-VOC treatment is based on two antibodies including casirivimab and imdevimab, which are supplied as a single dose in a 1: 1 ratio that is administered intravenously (IV) or subcutaneously (SC). The first results of their phase II study are presented in their recent study published on the preprint server medRxiv*.

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

Nasopharyngeal (NP) swabs and blood cells were taken every other day for the first week, then monthly for the next four months. All study participants were over 18 years of age and had a positive SARS-CoV-2 test result less than or equal to 72 hours before randomization. No patient considered to be at risk of developing more severe COVID-19 was included in the study.

Non-control patients who were eligible received a single dose of REGEN-COV administered IV or SC. IV doses ranged from 300 to 2400 milligrams (mg), while SC doses were only given to 600 or 1200 mg.

While health workers, providers and patients were blinded to the control group and dose, it was not possible to blind them to the method of administration. The researchers were mainly studying the change in the baseline viral load in NP samples during the first seven days. Notably, the researchers also looked at the number of unwanted 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 the treatment group as the fixed effect and the viral load and baseline treatment as covariates.

Study results

Of the total 815 patients, 523 were assigned to IV therapy and 292 were assigned to SC therapy. No severe cases of COVID-19 developed during the trial. About 90% of patients had low risk symptoms and the rest were asymptomatic.

The researchers found that IV and SC doses of REGEN-COV significantly reduced viral load up to day 7. The most effective reduction in viral load was seen when 2400 mg was administered intravenously.

At 1200 mg, SC and IV reduced viral load equally, and the dose administered during SC administration did not affect the reduction in viral load. The IV dose tended to result in a steady reduction in antibody concentration over the seven days, while the SC dose resulted in an almost maximum level of REGEN-VOC concentration on day 33, although it was continued to increase slowly until the seventh day.

There were no serious safety concerns, although one patient experienced a mild reaction. Two other safety issues were determined to be unrelated to the drug.

Conclusion

The authors point out how the drug showed significant reductions in viral load at all doses and rapid absorption of REGEN-COV into the body after administration by either route. The lack of safety concerns, combined with linear and proportional pharmacokinetics, suggests the drug is safe for further testing in patients with more severe COVID-19 and those at risk of progressing to a more severe prognosis.

While higher doses resulted in an increased reduction in viral load, the researchers point out that even the lowest dose showed antibody concentrations reaching between 60 and several hundred times the amount required to neutralize most VOCs. , suggesting that lower doses may 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 that are beginning to approach availability will be a relief for policymakers. public health and health workers. In addition, the availability of these antivirals should allow more informed decisions for the treatment of patients and any need to reintroduce restrictions.

*Important Notice

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