Intramuscular Sotrovimab Viable for COVID-19, May Expand Outpatient Management

Results of a study published in Open Forum Infectious Diseases show that the intramuscular (IM) administration of sotrovimab for the treatment of COVID-19 infection is well tolerated and noninferior to intravenous (IV) administration.

Researchers conducted a randomized, multicenter, open-label, phase 3 study from June to August 2021 to evaluate the noninferiority of IM to IV administration of sotrovimab. The researchers used an absolute noninferiority margin of 3.5%. Eligible patients were infected with COVID-19, aged 12 years and older, at increased risk for severe disease progression, and not receiving supplemental oxygen. Patients were randomly assigned 1:1:1 to receive sotrovimab as either a single 500-mg IV infusion, a 500-mg IM injection, or a 250-mg IM injection. Patients were stratified by age (12-17, 18-64, and ≥65 years), COVID-19 vaccination status, and geographic region.

The primary composite endpoint was all-cause hospitalization for more than 24 hours for acute management of any illness or all-cause mortality through day 29. The patients in each group who met the primary endpoint were compared via binomial regression and identity link function, with adjustments for treatment group, age (<65 vs ≥65 years), and sex.

The primary analysis included a total of 937 patients, of whom 378 were in the 500-mg IV infusion group, 376 were in the 500-mg IM injection group, and 183 were in the 250-mg IM injection group. Overall, demographic and baseline characteristics were balanced between the groups, though most patients were Hispanic (range, 83%-86%) and 23% were aged 65 years and older.

Approximately one-third of the study population had at least 2 risk factors for severe disease progression, the most common of which were obesity, older age, chronic lung disease, and diabetes. In addition, 86% to 88% of patients had experienced COVID-19 symptoms for at least 5 days at the time of enrollment.

The percentage of patients who met criteria for the primary endpoint was 2.7% for those in the 500-mg IM injection group and 1.3% for those in the 500-mg IV infusion group (adjusted absolute risk difference [aRD], 1.06%; 95% CI, -1.15 to 3.26), indicating noninferiority between administration routes.

Further, 2.4% of patients in the 500-mg IV infusion group and 3.2% of those in the 500-mg IM injection group experienced a composite of COVID-19 progression to all-cause emergency department admission, all-cause hospitalization for any duration, or all-cause mortality (aRD, 0.86%; 95% CI, -1.56 to 3.28).

In a safety analysis, the overall incidence of adverse events (AEs) through week 12 was low and similar between patients who received IV vs IM sotrovimab administration. The overall rate of severe AEs was also low (range, <1%-2%), none of which were attributed to sotrovimab treatment. The most commonly reported drug-related AEs were COVID-19 and COVID-19 pneumonia.

Of note, mortality following severe drug-related AEs occurred among 2 patients in the 500-mg IM injection group and 2 patients in the 250-mg IM injection group.

Following sotrovimab receipt, no between-group difference in the change in SARS-CoV-2 viral load was observed during the 36-week follow-up period.

Study limitations include insufficient racial and geographic diversity, as most patients were Hispanic and enrollment occurred primarily in Florida. Missing data and the low percentage of immunocompromised patients (3%) were also noted as limitations.

In regard to COVID-19 management, “The availability of a therapy that can be administered by the IM route will be especially critical for underserved populations and those without access to IV infusion centers,” the researchers concluded.

Disclosures: This study was supported by Vir Biotechnology, Inc. in collaboration with GlaxoSmithKline. Multiple study authors declared affiliations with pharmaceutical, biotech, and/or device companies. Please see the original reference for a full list of disclosures.