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Administering the monoclonal antibody sotrovimab intramuscularly was noninferior to the intravenous (IV) route for high-risk COVID patients, a researcher said.

The risk difference between groups for hospitalization longer than 24 hours for acute management of severe illness or death was 1.07% (95% CI -1.25% to 3.39%), and the upper bound of the confidence interval was lower than the 3.5% noninferiority margin set by the FDA, reported Anita Kohli, MD, of Arizona Clinical Trials in Tucson.

Safety was comparable for intramuscular versus IV administration of sotrovimab, with no treatment-related serious adverse events (AEs), she said at a press conference at the virtual Conference on Retroviruses and Opportunistic Infections (CROI).

Sotrovimab, which gained emergency use authorization in May 2021, was the only monoclonal antibody to be recommended for high-risk COVID patients by NIH COVID guidelines due to evidence of activity against Omicron.

Kohli also noted that lab tests of pseudovirus activity showed sotrovimab was active against the BA.2 mutation as well.

While currently only available as an IV infusion, Kohli said that intramuscular administration of sotrovimab could "meet a significant unmet medical need," as it will "allow for increased access for patients in need of urgent treatment."

She added that it is also a more convenient method of administration that requires less infrastructure compared to an IV infusion, and one that has the potential to be available in clinical settings, patient homes, and retail pharmacies.

The COMET-TAIL study was a involving COVID patients ages 12 and up who were at high risk of progressing to severe disease and had symptoms for fewer than 7 days. They were initially randomized 1:1:1 to receive 500 mg IV sotrovimab, 500 mg intramuscular sotrovimab, or 250 mg intramuscular sotrovimab, but the third arm was discontinued following a safety review that suggested an increased rate of hospitalizations.

Patients were enrolled from June to August 2021, during the Delta surge. Of the participants, 50%-58% were female, a large majority were of Hispanic or Latino ethnicity (82%-85%), a little less than two-thirds had obesity, and a little less than half were age 55 and up (median age 51-52).

Overall, the efficacy population consisted of 378 in the IV arm and 376 in the intramuscular arm. Ten people in the intramuscular group were hospitalized for at least 24 hours or died compared to five in the IV arm.

There were two deaths in the study, both in the intramuscular arm. Kohli explained that one patient was a man with a BMI of 69, who "may have not received the appropriate dose" of treatment, and the other was an 82 year-old man who was admitted with pneumonia, received mechanical ventilation and had a do-not-resuscitate order.

"The company is doing [pharmacokinetics] work to understand if there are any signals" from the high BMI patient who died, Kohli said, "so we'll learn more as we go along there."

Patients in the intramuscular arm received two injections of sotrovimab "in the dorsogluteal muscle," and there was only one grade 3 AE (tenderness), with the rest being grade 1 or 2.

When asked if intramuscular sotrovimab had the potential to be self-administered, Kohli responded that different formulations of the drug are being developed in different concentrations "so it can be given in alternate intramuscular locations."

CROI Chair, Elaine Abrams, MD, of Columbia University Medical Center in New York City, who moderated the press conference but was not involved in the research, asked where the drug fits on the "treatment to prevention" spectrum.

"Right now, it's certainly a treatment drug, but prevention trials are coming ... and we're excited to see that data," Kohli said.

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