The severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2, which is responsible for the coronavirus outbreak 2019 (COVID-19), has infected almost every country on the world and has caused more than five million deaths. The rapid transmission rate of SARS-CoV-2 caused many countries to enact restrictive and costly social distancing measures including mandatory face masks, closure of public spaces, and even lockdowns/stay-at-home orders.
While some developed nations have initiated mass vaccination campaigns that have allowed a majority of the restrictions to be lifted, many developing countries are unable to provide the logistics or resources to support the vast cold chains needed to ensure adequate storage of vaccines. SARS-CoV-2 variants that are considered to be of concern (VOCs) that have a higher transmission rate and infectivity, as well as the capability to overcome natural or vaccine-induced immunity, continue to be developed.
Study Phase 2 dose-ranging research of the virologic efficacy and safety of the combination COVID-19 antibody imdevimab and casirivimab in the outpatient setting. Image Credit: SmartPhotoLab / Shutterstock.com
About the study
Regeneron Pharmaceuticals has been developing a new drug to address the growing need for COVID-19 treatment. The REGEN COV treatment is based around two antibodies including imdevimab and casirivimab, which are provided in a single dose, at a 1:1 ratio that is administered intravenously (IV) or subcutaneously (SC). Initial results from their Phase II study are published in their most recent study that was published on the preprint server medRxiv*.
Researchers conducted an randomized double-blind study with parallel control groups receiving placebos. The study looked at different doses.
Nasopharyngeal (NP) swabs and blood cells were collected every other day for the first week, and monthly for the next four months. All participants were at least 18 years old and had received the positive result of the SARS/CoV-2 test within 72 hours of being randomly assigned. The study included no patients who were thought to be at greater risk of developing COVID-19.
Patients who were not part of the control group and who were eligible for treatment received one dose of REGENCOV either by IV or SC. The doses for IV were between 300 and 2,400 milligrams (mg) while the SC doses were 600 mg or 1,200 mg.
Although patients, healthcare providers as well as healthcare workers were blinded to the dose and the control group, it was not possible to blind them from the method of administration. The primary focus of the research team was to study the changes in baseline viral levels in NP samples throughout the first seven days. Additionally, the researchers looked at the amount of adverse and serious adverse effects.
In all 815 patients were enrolled in the study. A ANCOVA model was applied to the data to conduct statistical analysis. It utilized the treatment group as a fixed effect, the baseline viral load and treatment as covariates.
Out of the total 815 patients 523 were assigned to IV treatment, while 292 were assigned to SC treatment. No serious cases of COVID-19 developed during the trial. About 90% of patients showed symptoms of low-risk, while the rest were asymptomatic.
The researchers found that both IV and SC administered doses of REGEN COV significantly reduced the amount of viral burden until the seventh day. 2,400 mg IV was the most effective in reducing the amount of viral infection.
The viral load was decreased equally by SC and IV at 1,200 mg. The SC dose administered when SC was administered did not impact the viral load. The IV dose was more likely to result in an ongoing decrease in antibody concentration over all seven days, while the SC dose produced the REGEN-COV concentration to be close to its maximum concentration on day three, but it continued to rise slowly until day seven.
There were no serious safety concerns, but one patient did show a mild reaction. Two other safety concerns were not related to the medication.
The authors point out that the drug has shown significant reductions in viral load at all doses and the rapid absorption of REGENCOV into the body following administration by any route. In addition, given the absence of safety concerns with linear and proportional Pharmacokinetics, the drug is expected to be safe for ongoing testing in patients with more severe COVID-19 or at greater chance of developing a less favorable prognosis.
While higher doses resulted increased viral load reduction, the researchers point out that even the smallest dose indicated antibody concentrations that ranged between 60 and several hundredfolds of the needed amount to neutralize the majority of VOCs which suggests that lower doses are worth investigating.
VOCs are increasing their ability to evade vaccine-induced and natural immunity. This should provide relief to healthcare professionals and public health policymakers. Furthermore the availability of these antivirals could provide more information for the treatment of patients and the need to reintroduce restrictions.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information
Content Source: https://www.news-medical.net/news/20211115/Promising-results-from-Phase-II-REGEN-COV-study.aspx