COVID-19, the syndrome caused by SARS-CoV-2 infection, is notable for high hospitalization rates that can easily overwhelm local medical systems. Vaccine rollouts have begun, but the current number of diagnosed cases indicates that worldwide disruptions in hospital capacity and high mortality rates are likely to continue. Some therapeutics being studied, such as the antiviral drug remdesivir, have been found to demonstrate efficacy in shortening hospital stays and reducing overall mortality. However, additional research is critically important to not only bringing more treatment options to the forefront, but to help understand how these options may function when combined with other treatments or administered across more patient types and populations.
A report in the New England Journal of Medicine describes interim results of one such study, the Phase 3 ACTIV-3/TICO (Therapeutics for Inpatients with COVID-19) trial of the LY-CoV555 antibody, which targets the SARS-CoV-2 spike protein, in hospitalized patients. This trial is part of the TICO platform, a master protocol to flexibly assess multiple candidate therapies in parallel using a similar trial design. At Day 5, patients who received the LY-CoV555 antibody infusion did not have better clinical outcomes than those who received placebo. Based on these data, the trial was stopped early for futility. Other trial arms testing different candidate therapies are ongoing.
Subgroup analyses also revealed no compelling trends toward a difference between the antibody- and placebo-treated groups. However, the assessment of clinical status categories at Day 5 was consistent with clinical status at later time points and with time to recovery, indicating that Day 5 outcomes will be useful for future studies, including ongoing studies in the TICO platform.
This multicenter study was supported by Baylor Scott & White Research Institute (BSWRI) with Uriel Sandkovsky, MD serving as the principal investigator. ACTIV-3/TICO enrolled 314 hospitalized patients at approximately one week after the onset of COVID-19 symptoms. All the study participants received remdesivir and also received supplemental oxygen and glucocorticoids when needed. LY-CoV555 (7000 mg) was delivered as a single one-hour intravenous infusion. The primary outcome was sustained recovery over 90 days.
The reasons for lack of LY-CoV555 effectiveness in hospitalized patients are unknown. The investigators offered several speculations, including potential issues with distribution of the antibody to the infected tissue, problems with potency, the possible development of viral mutants with reduced antibody binding, and harmful effects of the antibody that might negate any benefit in this patient population. Further investigation of these possible explanations is underway.
The safety of LY-CoV555 in this patient population is uncertain given the early termination but there were no differences observed between the antibody- and placebo-treated groups.
The researchers note that seemingly similar monoclonal antibodies may have profoundly different effects. As such, the TICO platform will continue to test additional therapies, including other antibodies targeting the SARS-CoV-2 spike protein, as candidate treatments for hospitalized COVID-19 patients.