FDA Authorizes Sotrovimab Monoclonal Antibody for Treatment of COVID-19

On May 26, 2021, the U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for the investigational monoclonal antibody therapy sotrovimab for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kilograms [about 88 pounds]) 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. This includes, for example, individuals who are 65 years of age and older or individuals who have certain medical conditions. The dosage of sotrovimab for the authorized use is a single IV infusion of 500 mg. Sotrovimab should be given as soon as possible after positive results of direct SARS-CoV-2 viral testing and within 10 days of symptom onset. Sotrovimab must be diluted and administered as a single intravenous infusion over 30 minutes.

The safety and effectiveness of sotrovimab continues to be evaluated for treatment of COVID-19. Sotrovimab is not authorized for patients who are hospitalized due to COVID-19 or require oxygen therapy due to COVID-19. This treatment has not shown benefit in patients hospitalized due to COVID-19 and monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients requiring high flow oxygen or mechanical ventilation. Additional information regarding Limitations of Authorized Use can be found in the Fact Sheet for Health Care Providers linked below.

Serious hypersensitivity reactions, including anaphylaxis, have been observed with administration of sotrovimab. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive care. Infusion-related reactions, occurring during the infusion and up to 24 hours after the infusion, have been observed with administration of sotrovimab. These reactions may be severe or life threatening. Consider slowing or stopping the infusion and administer appropriate medications and/or supportive care if an infusion-related reaction occurs. Additional information regarding these reactions can be found in the Fact Sheet for Health Care Providers linked below.

Mechanism of Action (MOA) and Pharmacokinetics (PK)

MOA: Sotrovimab is a monoclonal antibody that is specifically directed against the spike protein of SARS-CoV-2 and is designed to block the virus’ attachment and entry into human cells.

General PK: The mean (geomean) C_max following a 1 hour IV infusion of sotrovimab was 137 µg/mL (N = 129, CV% 40), and the mean (geomean) Day 29 concentration was 34 µg/mL (N = 78, CV% 23) from all subjects with an available Day 29 sample. It is expected that the half-life of sotrovimab is longer than Fc-unmodified IgG due to the LS modification, but data are not available.

Use in Specific Populations

The effect of different covariates (e.g., age, sex, race, body weight, disease severity, hepatic impairment) on the PK of sotrovimab is unknown. Renal impairment is not expected to impact the PK of sotrovimab since mAbs with molecular weight greater than 69 kDa do not undergo renal elimination. Similarly, dialysis is not expected to impact the PK of sotrovimab.

Pediatric Population

Sotrovimab is not authorized for use in pediatric patients under 12 years of age or weighing less than 40 kg. The safety and effectiveness of sotrovimab have not been assessed in pediatric patients. The recommended dosing regimen in patients 12 years to less than 18 years of age, weighing at least 40 kg, is expected to result in comparable serum exposures of sotrovimab as those observed in adults based on an allometric scaling approach (which accounted for effect of body weight changes associated with age on clearance and volume of distribution).

Efficacy and Safety

The issuance of an EUA is different than FDA approval. In determining whether to issue an EUA, the FDA evaluates the totality of available evidence and carefully balances any known or potential risks with any known or potential benefits of the product for use during an emergency. Based on the FDA’s review of the totality of the scientific evidence available, the agency determined that it is reasonable to believe that sotrovimab may be effective in treating adults and certain pediatric patients with mild-to-moderate COVID‑19. And, when used to treat COVID-19 for the authorized population, the known and potential benefits outweigh the known and potential risks for the drug. There are no adequate, approved, and available alternative treatments to sotrovimab.

Efficacy

The data supporting the EUA for sotrovimab are based on an interim analysis from a phase 1/2/3 randomized, double-blind, placebo-controlled clinical trial in 583 non-hospitalized adults with mild-to-moderate COVID-19 symptoms and a positive SARS-CoV-2 test result. Of these patients, 291 received sotrovimab and 292 received a placebo within five days of onset of COVID-19 symptoms. The primary endpoint was progression of COVID-19 (defined as hospitalization for greater than 24 hours for acute management of any illness or death from any cause) through day 29. Hospitalization or death occurred in 21 (7%) patients who received placebo compared to 3 (1%) patients treated with sotrovimab, an 85% reduction. Detailed information on the clinical trial and supporting data for this EUA can be found in the Fact Sheet for Health Care Providers linked below.

The FDA is carefully monitoring circulating viral variants and their sensitivity to monoclonal antibodies authorized to treat COVID-19, including sotrovimab. Laboratory testing showed that sotrovimab retains activity against the current circulating variants first reported in the United Kingdom, South Africa, Brazil, California, New York and India.

Safety

Potential side effects of sotrovimab include anaphylaxis and infusion-related reactions, rash and diarrhea. Additional adverse events associated with sotrovimab may become apparent with more widespread use. Detailed information on the safety of sotrovimab can be found in the Fact Sheet for Health Care Providers linked below.

Additional Information

The Fact Sheet for Health Care Providers provides essential information about using sotrovimab in treating COVID-19 as authorized and is available at https://go.usa.gov/x6aCD. A fact sheet for patients, parents, and caregivers is available at https://go.usa.gov/x6aCB and contains information for understanding the potential risks and potential benefits of taking sotrovimab, including side effects.

The EUA authority allows FDA to help strengthen the nation’s public health protections against chemical, biological, radiological, and nuclear threats by facilitating the availability and use of medical countermeasures needed during public health emergencies. For additional information on the EUA authority and EUAs for COVID-19, please visit https://go.usa.gov/xs8x4.

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This communication was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA.