By IDSE News Staff
The monoclonal antibody cocktail casirivimab and imdevimab (Regen-COV, Regeneron Pharmaceuticals) significantly reduced viral load within seven days of treatment in patients hospitalized with COVID-19, according to a presentation at IDWeek 2021, held virtually (abstract LB4).
In the phase 2/3, double-blind, placebo-controlled trial assessing casirivimab-imdevimab in 1,197 patients hospitalized with COVID-19, patients were randomly selected 1:1:1 to receive a one-time infusion of either high-dose (8,000 mg) casirivimab-imdevimab, a lower dose (2,400 mg) of casirivimab-imdevimab or the placebo standard-of-care treatment for COVID-19. There were 530 patients who entered the trial with no supplemental oxygen and 667 who were on low-flow oxygen.
All patients entering the trial were hospitalized with laboratory-confirmed COVID-19, and all received other background standards of care; 75% received corticosteroids and 55% received remdesivir (Veklury, Gilead).
On average, the patients had experienced symptoms for six days prior to entering the trial, and nearly half (43%) were seronegative, that is, they did not mount an antibody response. Approximately 30% were Hispanic and 12% were Black. Patients’ average age was 62 years, 54% were men and 46% were women.
Trial results presented at IDWeek showed that casirivimab-imdevimab significantly reduced the SARS-CoV-2 viral load in patients who were seronegative when they were hospitalized with COVID-19 and required low-flow or no supplemental oxygen (P=0.0172).
The clinical results also supported the much larger U.K. RECOVERY trial in hospitalized patients, with numerical improvements observed across all clinical end points assessed.
“We need a multifaceted approach to best manage the virus’s impact, including vaccination and effective treatment when patients become ill,” said Eleftherios Mylonakis, MD, PhD, a primary investigator of the trial and a professor of medicine, molecular microbiology and immunology, and the director of infectious disease at Brown University and the Lifespan Health System, in Providence, R.I. “These data show that Regen-COV can benefit certain patients even after they are hospitalized, reducing the amount of virus and clinical consequences.
The trial, which was stopped due to slow enrollment after recruiting just over one-third of the patients originally planned, found that patients who received either 2,400 or 8,000 mg of casirivimab-imdevimab in addition to standard-of-care treatment experienced numerical improvements across all clinical end points assessed, compared with standard of care alone.
The safety analysis included results from all patients in the efficacy analysis plus additional patients from earlier stages of the clinical program who were on low-flow oxygen at baseline.
In a safety analysis involving 2,007 patients (casirivimab-imdevimab=1,340; placebo=667), serious adverse events occurred in 21% of casirivimab-imdevimab patients (n=285) and 26% of placebo patients (n=174). Infusion-related and hypersensitivity reactions that were grade 2 or more occurred more commonly among casirivimab-imdevimab than placebo patients.
“Taken together with results announced earlier this year from the RECOVERY trial and other studies, these results have the potential to inform personalized care for hospitalized patients with this protean disease that presents with such high clinical variability,” Dr. Mylonakis said.
The trial originally assessed a broader group of patients; however, in late 2020, the trial began to exclude patients who were on mechanical ventilation or high-flow oxygen at baseline based on a potential safety signal identified by an independent data monitoring committee in 199 patients on mechanical ventilation or high flow-oxygen, a finding that was not replicated in the much larger RECOVERY trial that enrolled hospitalized patients with a broad range of severe COVID-19, including these patient groups.
George D. Yancopoulos, MD, PhD, the president and chief scientific officer at Regeneron, said the results show that casirivimab-imdevimab can change the course of illness for a variety of patients with COVID-19, including those who are hospitalized.
The casirivimab-imdevimab antibody cocktail is authorized in the United States under an emergency use authorization to treat people who are at high risk for serious consequences from COVID-19 infection who are either already infected, but not hospitalized, or for post-exposure prophylaxis in certain settings.
