INTRAMUSCULAR SOTROVIMAB IS NONINFERIOR to INTRAVENOUS SOTROVIMAB for COVID-19

ABSTRACT

Background: Sotrovimab is a pan-sarbecovirus neutralizing monoclonal antibody shown to be safe and effective for the treatment of early COVID-19 in high-risk patients and retains activity against variants of concern, including delta and omicron. To facilitate wider access to sotrovimab, it was formulated to allow for either intramuscular (IM) or intravenous (IV) administration. Methods: COMET-TAIL (NCT04913675) is a Phase III, randomized, multicenter, open-label, noninferiority (NI) study of IM vs IV sotrovimab for the treatment of mild/moderate COVID-19 in participants ≥12 years of age at high risk of disease progression. Participants were randomized to receive sotrovimab by single 500 mg IV infusion or IM injection (500 mg or 250 mg). The primary objective was to evaluate the efficacy of 500 mg IM vs 500 mg IV sotrovimab in preventing hospitalization for >24 hours for acute management of illness due to any cause or death. The 250 mg IM arm discontinued early due to a greater number of hospitalizations seen in that arm. A 3.5% NI margin on the risk difference scale was prespecified. Results: COMET-TAIL enrollment occurred from Jun-Aug 2021, coinciding with a surge in the SARS-CoV-2 delta variant in southern USA. The majority (∼85%) of participants were Hispanic or Latino and ∼25% were ≥65 years of age. In the 500 mg IM sotrovimab arm, 10/376 (2.7%) participants compared with 5/378 (1.3%) in the sotrovimab 500 mg IV arm met progression criteria for the primary endpoint (adjusted risk difference 1.07% [95% CI-1.25%, 3.39%]), meeting the NI margin of 3.5%. The overall rate of adverse events and injection/infusion-related reactions was low and similar between the 500 mg treatment arms. Most injection-site reactions were mild (grade 1), occurred shortly after dosing, and were limited in duration. Disease-related events (DREs) were balanced between the 500 mg IV and 500 mg IM arms. The most frequent DREs were COVID-19 pneumonia and pneumonia. There was a low percentage of participants (∼1%) with serious adverse events across all treatment arms, and none were considered related to treatment. Two participants (1 with BMI 69 mg/kg2 and an 82-year-old man) in the 500 mg IM arm died due to progression of COVID-19;no deaths occurred in the 500 mg IV arm. Conclusion: In the COMET-TAIL trial, sotrovimab given by 500 mg IM injection was found to be noninferior to IV infusion and was well tolerated. The option of IM administration will expand the potential for outpatient treatment with sotrovimab.