IM noninferior to IV sotrovimab for COVID-19

In high-risk nonhospitalized patients with mild-to-moderate COVID-19, intramuscular administration of the monoclonal antibody sotrovimab was noninferior to IV infusion of the drug, according to findings from the phase III COMET-TAIL trial presented at CROI 2022.

In patients with mild-to-moderate COVID-19 who are at high risk of progression, sotrovimab 500 mg IV significantly reduced the risk of all-cause hospitalization or death. [N Engl J Med 2021;385:1941-1950; medRxiv 2021;doi:10.1101/2021.11.03.21265533] Sotrovimab has potent neutralizing activity against highly emerging variants including Delta and Omicron, which may be resistant to other monoclonal antibodies. [bioRxiv 2021;doi:10.1101/2021.03.09.434607]

“Sotrovimab administered intramuscularly can meet a significant unmet medical need,” said Dr Anita Kohli from Arizona Liver Health, Chandler, Arizona, US. “[It could provide a] more convenient method of administration [which could] increase access to care, requires less infrastructure than IV infusion, and has the potential to be made available in most clinical settings, patient homes, and retail pharmacies.”

A total of 982 COVID-19-positive patients (median age 52 years, 25 percent ≥65 years, 54 percent female) were randomized 1:1:1 to receive sotrovimab 500 mg IM or IV, or 250 mg IM. However, the 250-mg dose was discontinued early due to safety reviews revealing increased hospitalization rate compared with the 500-mg doses. Sotrovimab IM was administered as two 4-mL injections in the bilateral dorsogluteal muscles. [CROI 2022, abstract 102]

In the overall cohort, the most common risk factors for COVID-19 progression were obesity (62 percent), age ≥55 years (43 percent), and chronic lung disease (17 percent). About 30 percent of participants had ≥2 risk factors, and up to 14 percent had a symptom duration of >5 days. The primary endpoint was the efficacy of sotrovimab to prevent hospitalization for >24 hours for acute management of illness due to any cause or death.

After exclusions following protocol amendments, 376 patients received IM sotrovimab while 378 received IV sotrovimab. Of these, 2.7 percent and 1.3 percent of participants in the respective IM and IV arms met the primary endpoint. This resulted in an adjusted risk difference of 1.07 percent.

“Looking at the upper limit of the 95 percent confidence interval of 3.39 percent, this was lower than the prespecified noninferiority margin of 3.5 percent. For this reason, sotrovimab 500 mg IM was concluded to be noninferior to sotrovimab 500 mg IV,” explained Kohli.

Adverse events (AEs), serious AEs, and disease-related events (DREs; ie, AEs related to COVID-19 progression) were infrequent and balanced between the IM and IV arms (8 percent vs 7 percent [any AE], 1 percent vs <1 percent [any serious AE], and 3 percent vs 4 percent [any DRE]).

The incidence of infusion/injection-related reactions was also low in both arms (<1 percent for both). Solicited injection-site reactions (ISRs) were mostly grade 1, the most common being pain (8 percent) and tenderness (6 percent). Erythema/redness and induration/swelling were uncommon (≤1 percent). “All solicited ISRs were of limited duration and have resolved mostly by day 3,” said Kohli.

Two patients in the IM arm died prior to day 29 – one with a BMI of 69 kg/m² and another an 82-year-old male who was not resuscitated following disease progression due to his do-not-resuscitate status, noted Kohli.

“[Our] primary endpoint was met – treatment with sotrovimab 500 mg IM was noninferior to sotrovimab 500 mg IV,” said Kohli. “IM sotrovimab 500 mg administered as two 4-mL injections was well-tolerated, and [its] safety profile continues to be favourable … Higher concentration formulations of sotrovimab are in development to allow for alternate sites of IM injections.”

“The ability to administer sotrovimab via IM administration is anticipated to allow for wider access for patients in need of urgent treatment [and] will expand the potential for outpatient treatment with sotrovimab,” concluded Kohli.

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