Co-administration of bamlanivimab (formerly LY-CoV555), a monoclonal antibody to COVID-19, with remdesivir (Veklury) was ineffective for patients hospitalized with COVID-19, a randomized trial found.
There was no significant difference in sustained recovery over a 90-day period with the combination of remdesivir and placebo (ratio ratio 1.06, 95% CI 0.77-1.47), reported Dr. Jens Lundgren of the University of Copenhagen in Denmark and colleagues.
In addition, there was no significant difference in the primary safety outcome. The rate of experience of adverse outcomes (death, serious adverse events, or clinical grade 3 and 4 to day 5 adverse events) was 19% in the study group versus 14% in the placebo group (OR 1.56, 95% CI 0.78-3, 10), Str= 0.20), the authors wrote in New England Journal of Medicine.
As previously reported, the trial was adjourned in mid-October due to potential security concerns in this population. The authors noted that the Data and Security Oversight Board stopped enrollment due to uselessness 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 members on October 26.
The FDA approved Bamlanivimab in November for use in patients with COVID-19 with mild to moderate disease who were at high risk of progression to severe disease, but the agency stressed that the drug should not be used for patients with severe COVID-19 or for those who needed oxygen therapy.
ACTIV-3 (acceleration of therapeutic interventions and vaccines against COVID-19) is designed for early assessment of uselessness and safety after 300 patients, followed by enrollment in a full sample for agents who pass this initial assessment. Eligible patients were adults hospitalized with COVID-19 with symptom duration of 12 days or less.
From August 5 to October 13, 326 patients were enrolled at 31 sites, including 23 in the United States, seven in Denmark, and one in Singapore. In total, 163 patients received a bamlanivimab infusion, while 151 received a placebo infusion. All patients received remdesivir, as well as supplemental oxygen and glucocorticoids as needed. Almost all patients (95%) received remdesivir, the authors noted.
Patients had a mean age of 61 years, 44% were women, 47% were white, 21% were black, and 24% were Hispanic. Approximately half had a BMI over 30, and 68% had concomitant disease, including about half with hypertension who needed medication.
Although the primary outcome was a sustained recovery over a 90-day period, a provisional uselessness assessment was performed based on a regular scale for pulmonary function of seven categories, which showed no significant difference between bamlanivimab and placebo (OR 0.85, 95% CI 0, 56-1.29, Str= 0.45).
A similar percentage of patients developed organ dysfunction and serious infection (16% in the intervention group versus 14% in the placebo group).
Examining safety over 28 days, the 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, of which 12 of 14 were attributed to the worsening of COVID-19.
However, one limitation of these primary results with a median of only 31 days of follow-up is that the safety of bamlanivimab relative to placebo “remains uncertain,” in part due to smaller sample size and shorter follow-up, resulting in wide confidence intervals around major safety outcomes.
“These results indicate that LY-CoV555 is unlikely to improve outcomes among hospitalized patients with COVID-19,” the authors wrote.
This study was supported by Operation Warp Speed, 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 PETAL Research Triangle Institute (Prevention and Early Treatment of Acute Lung Injury) and the Cardiothoracic Surgical Examination Network; the U.S. Department of Veterans Affairs and the governments of Denmark, Australia, and the United Kingdom.
Trial drugs were donated by Gilead and Eli Lilly.
Lundgren did not reveal a conflict of interest. The co-authors revealed support from the National Institutes of Health, NIAID, the UK, the Medical Research Council, Brigham Young University, New York University, Oxford University, NHLBI, the U.S. Department of Defense, and various links to industry.