Administering bamlanivimab (formerly LY-CoV555), a monoclonal antibody for COVID-19, along with remdesivir (Veklury) was ineffective for patients hospitalized with COVID-19, a randomized trial found.
There was no significant difference in sustained recovery during a 90-day period with the combination compared to remdesivir plus placebo (rate ratio 1.06, 95% CI 0.77-1.47), reported Jens Lundgren, MD, of University of Copenhagen in Denmark, and colleagues.
In addition, there was no significant difference in the primary safety outcome. The rate of experiencing an adverse outcome (death, serious adverse events, or clinical grade 3 and 4 adverse events through day 5) was 19% in the investigational arm versus 14% in the placebo arm (OR 1.56, 95% CI 0.78-3.10, P=0.20), the authors wrote in the New England Journal of Medicine.
As previously reported, the trial was paused in mid-October due to potential safety concerns in this population. The authors noted that a data and safety monitoring board stopped enrollment for futility after 314 patients. A statement from the National Institutes of Health, which sponsored the so-called ACTIV-3 trial, said the trial was closed to new enrollees on October 26.
Bamlanivimab was authorized in November by the FDA for use in COVID-19 patients with mild to moderate disease who were at high risk of progressing to severe disease, but the agency emphasized the drug was not to be used for patients with severe COVID-19 or for those who required oxygen therapy.
ACTIV-3 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) was designed for an early futility and safety evaluation after 300 patients, followed by enrollment to the full sample size for agents that pass that initial assessment. Eligible patients were adults hospitalized with COVID-19 with symptom duration of 12 days or less.
From Aug. 5 to Oct. 13, 326 patients were enrolled at 31 sites, including 23 in the U.S., seven in Denmark and one in Singapore. Overall, 163 patients received an infusion of bamlanivimab, while 151 received an infusion of placebo. All patients received remdesivir, as well as supplemental oxygen and glucocorticoids when indicated. Nearly all patients (95%) received remdesivir, the authors noted.
Patients had a median age of 61, 44% were women, 47% were white, 21% were Black, and 24% were Hispanic. About half had a BMI over 30, and 68% had a co-existing illness, including about half with hypertension requiring medication.
While the primary outcome was sustained recovery during a 90-day period, an interim futility assessment was performed based on a seven-category ordinal scale for pulmonary function, which showed no significant difference between the bamlanivimab and placebo groups (OR 0.85, 95% CI 0.56-1.29, P=0.45).
A similar percentage of patients developed organ dysfunction and serious infection (16% in the intervention group vs 14% in the placebo group).
Examining safety through 28 days, a primary safety event occurred in 23% of the intervention group and 20% of the placebo group. There were 14 deaths — nine in the intervention group and five in the placebo, 12 of 14 of which were attributed to worsening COVID-19.
However one limitation to these primary results with a median of only 31 days of follow-up is that safety of bamlanivimab versus placebo “remains uncertain,” in part due to smaller sample sizes and shorter duration of follow-up that resulted in wide confidence intervals around major safety outcomes.
“These results indicate a low likelihood that LY-CoV555 improves outcomes among hospitalized patients with COVID-19,” the authors wrote.
This study was supported by the Operation Warp Speed program, the National Institute of Allergy and Infectious Diseases (NIAID) and Leidos Biomedical Research for the INSIGHT Network; the National Heart, Lung, and Blood Institute (NHLBI) and the Research Triangle Institute for the PETAL (Prevention and Early Treatment of Acute Lung Injury) Network and the Cardiothoracic Surgical Trials Network; the U.S. Department of Veterans Affairs, and the Danish, Australian, and U.K. governments.
Trial medications were donated by Gilead and Eli Lilly.
Lundgren disclosed no conflicts of interest. Co-authors disclosed support from the National Institutes of Health, NIAID, U.K.’s Medical Research Council, Brigham Young University, New York University, Oxford University, NHLBI, U.S. Department of Defense, and various ties to industry.