In patients hospitalized with coronavirus disease 2019 (COVID-19) without end-organ failure, combination therapy with LY-CoV555, a monoclonal antibody by Eli Lilly, and remdesivir did not demonstrate efficacy, according to a study published in The New England Journal of Medicine (TICO; ClinicalTrials.gov Identifier: NCT04501978).
In this platform trial of therapeutic agents, investigators randomly assigned patients in a 1:1 ratio to receive LY-CoV555 or matching placebo. All patients also received high-quality supportive care, including remdesivir and when indicated, supplemental oxygen and glucocorticoids. The treatment or placebo was given as a single intravenous infusion over the course of 1 hour. The primary outcome was a sustained recovery during a 90-day period, assessed in a time-to-event analysis. An interim futility assessment was performed on the basis of a 7-category ordinal scale for pulmonary function on day 5.
Of the 314 patients included in the study, 163 received LY-CoV555 and 151 received placebo. In total, 298 patients (95%) were receiving remdesivir before or on the day of randomization. At baseline, 49% of patients were receiving glucocorticoids and 51% of patients were receiving heparinoids.
Patients in each group were distributed across the 7 categories of the pulmonary ordinal outcome by day 5 in a similar manner, ranging from category 1 (minimal or no symptoms with usual activity) to category 7 (death). At day 5, 81 patients from each group was in either category 1 or 2.
Results showed that the odds ratio of patients being in a more favorable category in the LY-CoV555 group than the placebo group was 0.85 (95% CI, 0.56-1.29; P = .45). Overall, 143 patients (88%) in the LY-CoV555 group and 136 patients (90%) in the placebo group were discharged from the hospital (rate ratio, 0.97; 95% CI, 0.78-1.20).
The percentages of patients with organ dysfunction or serious infection were similar in both groups. By day 5, 31 patients (19%) in the LY-CoV555 group experienced a primary safety outcome, such as a composite of death, serious adverse events, or incident grade 3 or 4 adverse events compared with 21 patients (14%) in the placebo group (odds ratio, 1.56; 95% CI, 0.78-3.10).
On day 28 of follow-up, a primary safety event had occurred in 38 patients (23%) and 30 patients (20%) in the LY-CoV555 and placebo groups, respectively. Overall, 14 patients died: 9 from the LY-CoV555 group and 5 in the placebo group (hazard ratio, 2.00; 95% CI, 0.67-5.99). Worsening of COVID-19 was attributed as the cause for 12 deaths and cardiopulmonary arrest was the cause of 2 deaths.
The sample sizes and duration of follow-up were smaller than anticipated for this trial, resulting in wide confidence intervals around the major safety outcomes. The trial was also unable to make definitive statements about the safety of LY-CoV555 compared to placebo.
Investigators conclude that in this preliminary report of the first TICO trial, the neutralizing monoclonal antibody LY-CoV555 at a dose of 7000 mg did not result in better outcomes by day 5 compared to placebo. The TICO platform will continue to evaluate additional COVID-19 treatments.
Lundgren JD, Grund B, Barkauskas CE; ACTIVE-3/TICO LY-CoV555 Study Group. A neutralizing monoclonal antibody for hospitalized patients with Covid-19. New Engl J Med. Published December 22, 2020. doi:10.1056/NEJMoa2033130.