Lilly’s Antibody Combo Reduces Death, Hospitalization in Early COVID-19
Newly-announced data from Eli Lilly’s Phase III BLAZE-1 clinical trial show a combination of two of the company’s monoclonal antibodies, bamlanivimab (LY-CoV555) and etesevimab (LY-CoV016), significantly reduced the risk of hospitalization and death in high-risk patients with newly diagnosed coronavirus disease 2019 (COVID-19).
Bamlanivimab, a recombinant, neutralizing human IgG1 monoclonal antibody, directs itself against the spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The antibody blocks viral attachment and entry of the novel coronavirus into human cells.
Bamlanivimab is a product born from a collaboration between Lilly and AbCellera, with Lilly reportedly developing the therapy in under three months following discovery by AbCellera. The antibody received Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA) for COVID-19 in February.
Etesevimab represents another recombinant fully human monoclonal neutralizing antibody, this one licensed by Lilly from Junshi Biosciences. The antibody specifically binds to the surface spike protein receptor domain on SARS-CoV-2 and can block binding of the novel coronavirus to the ACE2 host cell surface receptor.
The study enrolled 769 high-risk patients 12 years of age and older who presented with symptomatic mild-to-moderate COVID-19. A total of 511 patients were randomly assigned to a combination of bamlanivimab 700 mg and etesevimab 1400 mg, while 258 patients were randomized to placebo. Treatments were administered in the outpatient setting and early in the course of the disease.
The primary outcome was the proportion of patients who experienced hospitalization or death from any cause by day 29.
Researchers observed four events in the bamlanivimab with etesevimab arm versus 15 events in patients taking placebo. This meant that treatment with the combination regimen led to an 87% reduction in the risk of hospitalization or death (p<0.0001). Key secondary endpoints – viral load, time to sustained symptom resolution, COVID-19-related hospitalization, and emergency room (ER) visit or death from any cause – were also improved with the monoclonal antibody combo.
The company said the findings were consistent with data from other analyses of the BLAZE-1 trial, including a previous Phase III cohort showing that treatment with bamlanivimab 2800 mg with etesevimab 2800 mg significantly reduced the risk of hospitalizations and deaths by 70%. A previous Phase II cohort also found that bamlanivimab monotherapy significantly reduced the risk of hospitalizations and ER visits by 70%.
There were four total deaths in the new Phase III cohort; these deaths were all attributable to COVID-19 and occurred in only patients who took placebo. To date, there have been no recorded deaths in patients who received bamlanivimab and etesevimab together in two Phase III cohorts of the BLAZE-1 trial.
In contrast, there have been 14 deaths in patients who have received placebo, with 13 of these events deemed related to COVID-19.
According to the company, the new findings from the BLAZE-1 trial offer additional safety and efficacy data to support the use of the studied dose recently granted EUA by the FDA. Additionally, the studied dose was also given a positive scientific opinion by the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP).
“These compelling data – in addition to the recent EUA from FDA, the CHMP decision from EMA and the recommendation for the therapy in the National Institutes of Health’s COVID-19 Treatment Guidelines – give healthcare providers additional information regarding the use of bamlanivimab and etesevimab together as a potentially life-saving treatment to help those most at risk for severe complications of COVID-19,” said Lilly’s chief scientific officer Daniel Skovronsky, M.D., Ph.D., who also serves as president of Lilly Research Laboratories “The consistent results observed in multiple cohorts of this trial over several months, even as new strains of COVID-19 have emerged, indicate bamlanivimab with etesevimab maintains its effects against a range of variants, particularly those circulating in the U.S.”