Eli Lilly’s BLAZE-1 study produced strong evidence that treatment with bamlanivimab plus etesvimab reduced risk of COVID-19 hospitalizations and death.
Eli Lilly and Company announced study results showing significant improvements in hospitalization and death rates among high-risk patients recently infected with coronavirus disease 2019 (COVID-19) with its antibody therapies.
Data from the phase 3 BLAZE-1 study demonstrated that bamlanivimab (LY-CoV555) with etesevimab (LY-CoV016), at 2800 mg each, reduced viral load and accelerated symptom resolution, according to investigators.
Bamlanivimab is a recombinant, neutralizing human immunoglobulin G 1 monoclonal antibody (mAb) that has been granted Emergency Use Authorization (EUA) by the FDA in 700 mg doses for the treatment of mild-to-moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in adults, as well as in children under the age of 12 and weighing at least 40 kg. Bamlanivimab has not been approved for any use in the US.
Etesevimab is a recombinant fully human mAb that also binds to the SARS-CoV-2 surface spike protein receptor binding domain.
The study included 1035 high-risk patients recently diagnosed with COVID-19 who either received the combination treatment or placebo. Investigators evaluated hospitalization and death – termed “events” in the study – in both study arms and determined 11 events (2.1%) in the treatment group. Within the placebo group, 36 events (7.0%) occurred, revealing a 70% risk reduction. Investigators recorded a total of 10 deaths, all of which stemmed from the placebo group.
“Notably, the 70% decrease in risk of hospitalizations or death seen in this Phase 3 trial of bamlanivimab and etesevimab together is consistent with the reduction in risk of hospitalization or ER visits seen with bamlanivimab alone in the Phase 2 trial,” said Daniel Skovronsky, MD, PhD, Lilly’s chief scientific officer and president of Lilly Research Laboratories. “Bamlanivimab alone is authorized for emergency use as a treatment for high-risk patients with mild to moderate COVID-19 in the US and widely available for use," he added.
In addition, the ongoing BLAZE-4 study is designed to determine the efficacy of lower doses of bamlanivimab and etesevimab together in high-risk patients early in the disease course of COVID-19. Pharmacodynamic data indicated that bamlanivimab 700 mg and etesevimab 1400 mg combination treatment is similar to the 2800 mg dosage for both drugs, and investigators are also seeking to evaluate even lower doses in order to maximize supply and minimize the burden on the health care system.
The safety profile for bamlanivimab and etesevimab together reflected previous observations from phase 1, phase 2, and phase 3 trials. Researchers reported that treatment with bamlanivimab has the potential for serious hypersensitivity reactions, including anaphylaxis. Infusion-relation adverse events may include fever, chills, nausea, headache, bronchospasm, hypotension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, and dizziness.
"These exciting results, which replicate positive Phase 2 data in a much larger set of patients, add valuable clinical evidence about the role neutralizing antibodies can play in fighting this pandemic. While the preliminary nature of Phase 2 results from COVID-19 neutralizing monoclonal antibodies may have limited acceptance of treatment, these Phase 3 data further strengthen the available evidence,” Skovronsky said.
Lilly submitted its EUA request to the FDA for bamlanivimab-etesevimab COVID-19 therapy in November and remains under review by the agency.