By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
In May 2021, the FDA issued an emergency use authorization (EUA) for the monoclonal antibody (mAb) sotrovimab to treat mild-to-moderate COVID-19. Sotrovimab is a recombinant human IgG1 kappa mAb that binds to the spike protein of SARS-CoV-2. Before December 2021, guidelines called for only two mAbs for this indication (bamlanivimab plus etesevimab and casirivimab plus imdevimab).1 With the emergence of the omicron variant, sotrovimab is of interest, since it might be the only mAb showing activity against this variant of concern. The microbiology and antiviral resistance section of the EUA was revised in December 2021.
INDICATIONS
The EUA for sotrovimab indicates the solution can be used to treat mild-to-moderate COVID-19 in adults and pediatric patients (age 12 years and older, weigh at least 40 kg) with positive SARS-CoV-2 viral testing and who are at high risk for progression to severe COVID-19, including hospitalization or death.2,3 High risks include age 65 years or older, BMI > 25kg/m2, diabetes, chronic kidney disease, immunosuppressive disease or treatment, cardiovascular disease, and neurodevelopment disorders. It is not authorized for patients who are hospitalized with COVID-19, who require oxygen, or require an increase in baseline oxygen flow rate because of COVID-19.
DOSAGE
The recommended dose is a single intravenous infusion (over 30 minutes) of 500 mg given as soon as possible after positive SARS-CoV-2 viral test and within 10 days of symptom onset. Sotrovimab is available as a single-dose 8 mL vial containing 500 mg.
POTENTIAL ADVANTAGES
In vitro neutralization data, artificial intelligence modeling, and anecdotal reports suggest sotrovimab is effective against the omicron variant while the other mAbs are not.2,4,5
POTENTIAL DISADVANTAGES
Serious hypersensitivity reactions, including anaphylaxis, have been observed.1 Infusion-related reactions may occur during and up to 24 hours after infusion. The benefit of sotrovimab has not been observed in hospitalized COVID-19 patients and may be associated with worse clinical outcomes when given to patients requiring high-flow oxygen or mechanical ventilation.1 As with all mAbs, coordinating intravenous infusion therapy may be problematic for some ambulatory patients with the appropriate indications for treatment.
COMMENTS
The clinical data supporting the EUA were based on an ongoing, randomized, double-blind, placebo-controlled trial in subjects with mild-to-moderate COVID-19 who were not hospitalized (Covid-19 Monoclonal Antibody Efficacy Trial-Intent to Care Early, or COMET-ICE).2,6 Subjects were randomized to sotrovimab (n = 528) or placebo (n = 529). The primary endpoint was progression of COVID-19 at day 29, defined as hospitalization for > 24 hours for acute management of any illness or death from any cause. Six subjects met these criteria in the sotrovimab group vs. 30 in the placebo group, adjusted relative risk reduction of 79% (95% CI, 50% to 91%). There were two deaths in the placebo group vs. zero in the sotrovimab group. The study results were released before the emergence of the omicron variant.
CLINICAL IMPLICATIONS
With the dominance of omicron and the significant reduced effectiveness of previously authorized mAbs, guidelines have been revised.1 For nonhospitalized patients with mild-to-moderate COVID-19 at high risk of disease progression, recommendations are (in order of preference): ritonavir-boosted nirmatrelvir (Paxlovid); sotrovimab; remdesivir on days 1, 2, and 3; and molnupiravir. Several factors affect the selection of the best treatment option for a specific patient, including the clinical efficacy of the treatment option, the supply/availability of the treatment option, the feasibility of administering parenteral medications (i.e., sotrovimab, remdesivir), the potential for significant drug-drug interactions, and the regional prevalence of omicron. There are no data on combining these therapeutic options. The cost of sotrovimab is $2,100 for a single treatment course.
REFERENCES
- National Institutes of Health. COVID-19 treatment guidelines. The COVID-19 treatment guidelines panel’s statement on therapies for high-risk, nonhospitalized patients with mild to moderate COVID-19. Last updated Jan. 19, 2022. https://bit.ly/3fXqmjy
- GlaxoSmithKline sotrovimab fact sheet for HCP. December 2021.
- U.S. Food & Drug Administration. Emergency use authorization 100. Dec. 16, 2021.
- Llorente E. Just one monoclonal antibody drug works against omicron. It’s in short supply at N.J. hospitals. NJ.com. Jan. 7, 2022.
- Chen J, Wang R, Gilby NB, Wei GW. Omicron variant (B.1.1.529): Infectivity, vaccine breakthrough, and antibody resistance. J Chem Inf Model 2022;62:412-422.
- Gupta A, Gonzalez-Rojas Y, Juarez E, et al. Early treatment for COVID-19 with SARS-CoV-2 neutralizing antibody sotrovimab. N Engl J Med 2021;385:1941-1950.
In vitro neutralization data, artificial intelligence modeling, and anecdotal reports suggest sotrovimab is effective against the omicron variant while the efficacy of other monoclonal antibodies appears to wane.
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