Lilly’s Phase III Combination Antibody Trial for COVID-19 Shows 87% Risk Reduction

Lilly’s Phase III Combination Antibody Trial for COVID-19 Shows 87% Risk Reduction
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Eli Lilly said its antibody combination of bamlanivimab (LY-CoV555) 700 mg and etesevimab (LY-CoV016) 1400 mg—already FDA-authorized for emergency use—generated additional positive Phase III results, slashing by 87% the risk of  COVID-19 related hospitalizations and deaths in high-risk patients recently diagnosed with the virus.

Four hospitalizations and deaths, or “events,” occurred in patients 29 days after treatment with the bamlanivimab-etesevimab combination, compared with 15 reported in patients given placebo in the randomized, double-blind, placebo-controlled BLAZE-1 Phase III trial (NCT04427501), Lilly said.

The data came from a newly reported cohort of 769 high-risk patients aged 12 and older with mild to moderate COVID-19. Of those patients, 511 were randomized to therapy, and the other 258 to placebo. The study’s key endpoint was the percentage of participants who experience COVID-related hospitalizations or death from any cause by day 29.

Lilly added that bamlanivimab and etesevimab together also showed statistically significant improvements on key secondary endpoints—defined as change from baseline to day 7 in SARS-CoV-2 viral load, persistently high SARS-CoV-2 viral load on day 7, time to sustained symptom resolution, and COVID-related hospitalization, ER visit, or death from any cause from baseline by day 29.

Additional endpoints in BLAZE-1 included change from baseline in viral load at other time points, symptom improvement, symptom resolution, as well as safety.

“These positive results reinforce our previous findings and support the authorized dose of bamlanivimab 700 mg with etesevimab 1400 mg,” Daniel Skovronsky, M.D., Ph.D., Lilly’s chief scientific officer and president of Lilly Research Laboratories, said yesterday in a statement. “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 United States.”

Bamlanivimab (LY-CoV555) is a neutralizing immunoglobulin G, subclass 1 (IgG1) monoclonal antibody designed to bind to the receptor-binding domain of the spike protein of SARS-CoV-2. The antibody was first identified in a blood sample from a recovered COVID-19 patient, and discovered through the rapid pandemic response platform of partner AbCellera, in partnership with NIAID’s Vaccine Research Center.

Etesevimab (LY-CoV016, also known as JS016) is a recombinant fully human monoclonal neutralizing antibody, which specifically binds to the SARS-CoV-2 surface spike protein receptor-binding domain with high affinity and can block the binding of the virus to the ACE2 host cell surface receptor.

Bamlanivimab—authorized for emergency use by itself last year—and the combination with etesevimab are among 21 “Front Runner” leading candidates among the more than 300 COVID-19 therapeutics under study in GEN’s “COVID-19 Drug & Vaccine Candidate Tracker.”

70% risk reduction

In January, Lilly shared results from a BLAZE-1 cohort of 1,035 patients showing a higher dose of the antibody combination—bamlanivimab 2800 mg with etesevimab 2800 mg—reduced the risk of hospitalizations and deaths by 70%. Lilly reported 11 events (2.1%) in patients receiving its antibody combination, compared with 36 events (7%) in placebo patients.

That decrease was also consistent with the 70% reduction in risk of hospitalization or ER visits seen with bamlanivimab alone in the Phase II portion of BLAZE-1, the company said.

Across the two cohorts of the Phase III study analyzed to date, Lilly said, no deaths had occurred in patients receiving treatment with bamlanivimab and etesevimab together, while 14 deaths took place in patients receiving placebo—of which 13 were deemed COVID-19 related.

Bamlanivimab alone and bamlanivimab with etesevimab together have received emergency authorizations in Europe as well as the United States. Bamlanivimab alone is authorized for emergency use in countries that include Canada, Panama, Kuwait, the UAE, Israel, Rwanda, and Morocco.

In Rwanda and Morocco, Lilly is providing bamlanivimab free through the Bill & Melinda Gates Foundation.