Sotrovimab
Introduction to Sotrovimab
Sotrovimab is a recombinant human IgG1κ monoclonal antibody that binds to a highly conserved epitope on the spike protein receptor binding domain of SARS-CoV-2. It was developed by GlaxoSmithKline and Vir Biotechnology and received Emergency Use Authorization (EUA) from the FDA in May 2021 for the treatment of mild-to-moderate COVID-19 in high-risk patients. However, as of April 2024, its EUA has been revised due to the emergence of resistant variants.
Mechanism of Action
Sotrovimab works through two primary mechanisms:
- Virus Neutralization: It binds to an epitope on the SARS-CoV-2 spike protein that is shared with SARS-CoV-1 (the virus that causes SARS), blocking viral attachment and entry into human cells.
- Effector Function: The Fc region of sotrovimab has been engineered for extended half-life and to engage innate immune functions. This may result in clearance of virus-infected cells through antibody-dependent cell-mediated cytotoxicity (ADCC) and phagocytosis.
The conserved nature of its target epitope was initially thought to reduce the likelihood of escape mutations, although resistant variants have since emerged.
Indications
As of April 2024, sotrovimab's indications have evolved due to the changing landscape of SARS-CoV-2 variants:
- Original EUA (May 2021): Treatment of mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death.
- Revised EUA (April 2024): The FDA has limited the use of sotrovimab only in regions where it is likely to retain activity against circulating SARS-CoV-2 variants. Healthcare providers should monitor the FDA website for information on specific variants and geographic regions where sotrovimab is currently authorized.
Note: The exact status and indications may have changed after April 2024. Healthcare providers should always refer to the most current FDA guidance.
Administration
When authorized for use, sotrovimab is administered as follows:
- Dosage: 500 mg
- Route: Intravenous (IV) infusion
- Duration: Single dose given over 30 minutes
- Timing: Should be given as soon as possible after positive SARS-CoV-2 test and within 10 days of symptom onset
Important notes:
- Sotrovimab must be diluted prior to administration
- Patients should be monitored during the infusion and for at least 1 hour after completion
- It should be administered in a setting where severe hypersensitivity reactions can be managed
Efficacy and Safety
Efficacy:
- The COMET-ICE trial demonstrated an 85% reduction in hospitalization or death compared to placebo in high-risk adult outpatients with mild-to-moderate COVID-19
- Efficacy against emerging variants has varied, leading to changes in authorization status
Safety:
- Most common adverse events: Rash (2%), diarrhea (1%), bronchitis (1%)
- Serious adverse events: Anaphylaxis and infusion-related reactions have been reported
Limitations:
- Decreased efficacy against certain SARS-CoV-2 variants
- Not authorized for patients hospitalized due to COVID-19 or who require oxygen therapy
- Not a substitute for vaccination against COVID-19
Pediatric Use
Sotrovimab's use in pediatric patients has been limited:
- Initially authorized for use in patients 12 years and older weighing at least 40 kg
- Safety and efficacy in pediatric patients under 12 years of age have not been established
- Limited data available on use in pregnant adolescents
Considerations for pediatric use:
- Benefit-risk assessment should be conducted for each patient, considering the changing landscape of SARS-CoV-2 variants
- Pediatricians should stay informed about the latest FDA guidance on sotrovimab's authorization status
- Other treatment options may be preferred in pediatric patients, depending on current guidelines and variant prevalence
Special Considerations
- Variant Monitoring: Healthcare providers must stay informed about the prevalence of SARS-CoV-2 variants in their region and sotrovimab's activity against them.
- Pregnancy and Lactation: Limited data available. Should be used during pregnancy only if the potential benefit outweighs the potential risk for the mother and fetus.
- Drug Interactions: No formal drug interaction studies have been conducted.
- Vaccination: COVID-19 vaccines may be less effective if administered within 90 days of sotrovimab treatment.
- Antiviral Resistance: The potential for treatment-emergent resistance should be considered, especially in immunocompromised patients.
- Long-term Effects: As a relatively new therapy, long-term effects are not yet known and patients should be monitored accordingly.
- Cost and Availability: These factors may influence treatment decisions, especially given the changing authorization status.
