Sotrovimab was a specific medical treatment developed for COVID-19, representing a class of medicines known as monoclonal antibody therapy. The initial goal of this treatment was to help prevent severe disease in certain patients who contracted the SARS-CoV-2 virus.
Sotrovimab’s Mechanism of Action
Sotrovimab functions as a monoclonal antibody, a laboratory-made protein designed to mimic the immune system’s natural ability to identify and neutralize foreign invaders like viruses. This therapeutic antibody was engineered to specifically target a stable region on the spike protein of the SARS-CoV-2 virus. This particular region, known as the receptor-binding domain, is relatively conserved across different viral strains.
By binding to this conserved epitope on the spike protein, sotrovimab physically blocks the virus from attaching to and entering human cells. The antibody also facilitates the immune system’s response by marking the virus for destruction through processes like opsonization and antibody-dependent cellular cytotoxicity (ADCC). Additionally, sotrovimab includes an engineered modification (M428L and N434S amino acid substitutions) that extends its presence in the body, potentially enhancing its distribution to the lungs.
Authorized Use and Patient Eligibility
Sotrovimab was granted an Emergency Use Authorization (EUA) by the U.S. Food and Drug Administration (FDA) in May 2021. This authorization permitted its use for treating mild-to-moderate COVID-19 in specific patient populations. To be eligible for treatment, individuals needed to be 12 years of age or older and weigh at least 40 kilograms.
Patients also required a positive SARS-CoV-2 viral test and had to be within 10 days of symptom onset. The therapy was intended for those considered to be at high risk of progressing to severe COVID-19, which included hospitalization or death. Sotrovimab was not authorized for patients who were already hospitalized due to COVID-19 or for those requiring oxygen therapy because of their COVID-19 illness.
Clinical Efficacy Against Evolving Variants
Clinical studies demonstrated sotrovimab’s effectiveness in reducing the risk of severe COVID-19 outcomes. The COMET-ICE study, a randomized, double-blind, placebo-controlled Phase 3 trial, evaluated the drug in high-risk adult outpatients with mild-to-moderate COVID-19. An interim analysis involving 583 patients revealed an 85% reduction in the risk of hospitalization lasting more than 24 hours or death by Day 29. Final results from the full study cohort of 1,057 patients confirmed a 79% reduction in these outcomes compared to placebo. Only about 1% of patients receiving sotrovimab experienced hospitalization or death, compared to 6% to 7% in the placebo group.
The effectiveness of sotrovimab faced challenges as the SARS-CoV-2 virus continued to evolve and new variants emerged. While initially effective against earlier strains, the Omicron variant and its subvariants, such as BA.2, BA.4, and BA.5, developed mutations in their spike proteins. These mutations significantly decreased sotrovimab’s ability to bind effectively to the virus in laboratory settings. As a result of this reduced efficacy against the dominant circulating variants, the FDA revoked the Emergency Use Authorization for sotrovimab in April 2022.
Administration and Potential Side Effects
Sotrovimab was administered as a single intravenous (IV) infusion. The recommended dose was 500 milligrams, infused over 15 to 30 minutes. Following the infusion, patients were usually monitored for at least one hour.
Sotrovimab had potential side effects. Common reactions included mild hypersensitivity symptoms such as rash, itching, nausea, dizziness, and diarrhea. More serious, though less frequent, adverse events could occur, including infusion-related reactions. These reactions might involve symptoms like fever, chills, headache, changes in blood pressure or heart rate, chest discomfort, fatigue, or altered mental status. A severe allergic reaction, known as anaphylaxis, was a rare but possible serious side effect.