Early treatment of COVID-19 with sotrobimab

Already, more than 170 million people are affected by the coronavirus pandemic known as Coronavirus Disease 2019 (COVID-19). The causative agent of COVID-19 is Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which is a highly infectious positive-strand RNA virus.

Scientists have found that the virus has serious implications for older patients, primarily with comorbidity such as diabetes, chronic lung disease, obesity, and chronic kidney disease. These individuals are more likely to be infected with the virus. Therefore, there is an urgent need for effective treatments for this vulnerable group.

Recent studies have shown that monoclonal antibody therapy can be effectively used to treat severely infected COVID-19 patients and help reduce hospitalizations. These antibodies can neutralize SARS-CoV-2. However, SARS-CoV-2 mutants are of concern because some antibodies that may have been obtained by previous COVID-19 infection or vaccination may not be useful against these mutants. Is causing.

Monoclonal antibodies that target evolutionarily conserved epitopes outside the rapidly changing receptor-binding motif may be one strategy for treating COVID-19 disease. These monoclonal antibodies are more effective against SARS-CoV-2 mutants because they have a non-overlapping resistance profile.

Recently, scientists have shown that monoclonal antibody therapy sotrobimab effectively neutralizes SARS-CoV-2. In addition, this engineered human monoclonal antibody can also neutralize many types of salvecoviruses, including SARS-CoV, the causative agent of SARS outbreaks decades ago. Sotrobimab was formerly known as VIR-7831.

New research published in medRxiv* We hypothesized that the preprint server could also target highly conserved epitopes using monoclonal antibodies capable of neutralizing all salvecoviruses. This conserved sequence is likely to remain unchanged in the SARS-CoV-2 mutant.

In the current study, sotrobimab was applied to highly infectious SARS-CoV-2 mutants identified in South Africa (B.1.351), the United Kingdom (B.1.1.7), and California (B.1.427 / B). It has been shown to restore its function. 1.429), and Brazil (P.1). Previous studies have reported the development of monoclonal antibodies against COVID-19 disease that may attach to receptor binding motifs associated with the angiotensin converting enzyme 2 (ACE2) receptor. However, because this domain is likely to mutate, monoclonal antibodies may remain ineffective against certain variants.

Researchers explain that sotrobimab contains Fc modifications of two amino acids called LS, which help increase half-life and bioavailability in the respiratory mucosa. This change will improve the therapeutic concentration for a long period of time. In vitro studies have revealed that sotrobimab has a strong effector function that can be used in immune-mediated viral clearance.

The current study conducted a pre-planned interim analysis of the efficacy test of the COVID-19 monoclonal antibody-safety and Effectiveness of Sotrobimab for the treatment of vulnerable populations of mild to moderate COVID-19 infections. Currently, the trial is closed for enrollment and is undergoing a data collection process such as safety, efficacy, initial immunogenicity, and test data.

Scientists found in a COMET-ICE study that a single dose of sotrobimab containing 500 mg resulted in hospitalization and mortality in a group of individuals vulnerable to COVID-19 disease compared to the results obtained using placebo. Revealed that it has significantly reduced.

The current study further reported that sotrobimab prevented one hospitalization for every 17 high-risk patients. COVID19 Symptoms..

Researchers have observed that even inpatients receiving sotrobimab do not require admission to the intensive care unit. This was not the case in patients who received placebo. The results strongly indicate that sotrobimab treatment for vulnerable individuals with COVID-19 prevented the severity of the disease.

Study design. R indicates randomization. * Patients were stratified by age (≤70 years vs.> 70 years), duration of symptoms (≤3 days vs. 4-5 days), and region. † The study pharmacist reconstituted and dispensed all study drugs within the same time frame to maintain blindness.

Another important aspect of this study was the inclusion of candidates for ethnic groups that were highly underestimated in previous clinical trials. Researchers reported that more than 60% of the study population consisted of COVID-19 patients who self-identified as Hispanic or Latin Americans.

This study revealed that sotrobimab is well tolerated among study populations without safety issues. Therefore, researchers have found that sotrobimab is an important treatment for COVID-19, especially in immunocompromised individuals whose vaccine may be ineffective against SARS-CoV-2 mutants or who may not respond to the vaccine. I think it can act as a medicine.

The current study evaluated more than 584,000 sequences in the Global Influenza Surveillance and Response System database (a global initiative for sharing all influenza data), with 99.96% conserved amino acid positions associated with sotrobimab epitopes in the virus. I found that. In addition, sotrobimab’s non-duplicate resistance profile allows it to bind antibodies that target currently approved receptor-binding motifs.

Despite the promising initial results, this study has some limitations. Only three hospitalizations were found in the sotrobimab group, which is not enough to draw a conclusion. In addition, the sample size that represents the safety dataset is medium in size. Secondary and exploratory endpoint analysis has been omitted from the current interim report due to ongoing research and therefore more data is needed to further emphasize and establish the benefits of sotrobimab. ..

*Important Notices

medRxiv Publish preliminary scientific reports that should not be considered definitive as they are not peer-reviewed, guide clinical practice / health-related behaviors, and should not be treated as established information.