The FDA last night granted Emergency Use Authorization (EUA) for a 700 mg dose of bamlanivimab (LY-CoV555) in combination with a 1400 mg dose of a second Lilly antibody candidate, etesevimab (LY-CoV016), for the treatment of mild to moderate COVID-19 in patients aged 12 and older who are at high risk for progressing to severe COVID-19 and/or hospitalization.

The EUA is the second for bamlanivimab, and comes three months after the agency authorized emergency use of the antibody by itself, administered via a single intravenous infusion at the lowest IV dose studied in clinical trials. As with the monotherapy EUA, before patients can be treated with the combination antibody therapy, they must weigh at least 40 kilograms (about 88 pounds) and be deemed at high risk for progressing to severe COVID-19 and/or hospitalization.

According to Lilly, bamlanivimab should be administered together via a single intravenous infusion as soon as possible after a positive COVID-19 test and within 10 days of symptom onset.

The FDA also authorized infusion times of 16 minutes for bamlanivimab and 21 minutes for the bamlanivimab-etesevimab combination—compared with the previously authorized time of 60 minutes. Lilly said it reduced the infusion times in response to feedback received from nurses and doctors administering the infusions.

“Bamlanivimab alone under emergency use authorization has already provided many people with an early treatment option that could prevent hospitalizations and we are excited to now add an additional therapeutic option with a similar demonstrated clinical benefit,” Daniel Skovronsky, MD, PhD, Lilly’s chief scientific officer and president of Lilly Research Laboratories, said in a statement. “Additionally, with the risk of resistance emerging as various strains of the virus arise, bamlanivimab and etesevimab together could potentially allow efficacy against a broader range of naturally occurring SARS-CoV-2 variants as these new strains spread around the world.”

The EUA is based on Phase III data from the Phase II/III BLAZE-1 trial (NCT04427501), a randomized, double-blind, placebo-controlled study. Of the 10 patients who died during the study, all were randomized to placebo, Lilly added.

Lilly reported 11 events (2.1%) in patients receiving its antibody combination, compared with 36 events (7%) in placebo patients—a 70% risk reduction among the study’s 1,035 patients. That decrease was consistent with the reduction in risk of hospitalization or ER visits seen with bamlanivimab alone in the Phase II portion of BLAZE-1, the company said.

The bamlanivimab-etesevimab combo also showed statistically significant improvements on all four key secondary endpoints—the change from baseline to day 7 in SARS-CoV-2 viral load, persistently high SARS-CoV2 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.

The data replicated earlier results published in JAMA in a much larger group of patients. Lilly said the outcomes seen with bamlanivimab and etesevimab together were consistent with the reduction in risk of hospitalization or ER visits seen with bamlanivimab alone. The most common adverse event more often reported for patients receiving bamlanivimab and etesevimab together vs. placebo was nausea on the day of infusion.

In granting the EUA, the FDA stated that bamlanivimab is not authorized for patients who are hospitalized due to COVID-19 or require oxygen therapy due to COVID-19, or require an increase in baseline oxygen flow rate due to COVID-19 among those on chronic oxygen therapy due to underlying non-COVID-19-related comorbidity.

1M Doses by mid-2021

In collaboration with Amgen, Lilly said it plans to manufacture up to 1 million doses of etesevimab for administration with bamlanivimab by mid-2021. There are 100,000 doses ready immediately and an additional 150,000 doses will be available throughout the first quarter, Lilly added.

Procurement and allocation of bamlanivimab and etesevimab together will follow the process created for bamlanivimab alone of making the therapy available directly to governments for allocation based on unmet needs, according to Lilly.

Bamlanivimab generated $871 million in revenues for Lilly last year, with the company projecting $1 billion to $2 billion in sales this year.

Washington has committed up to $1.5 billion in a pair of agreements toward bamlanivimab.

In December, the U.S. government exercised its option to purchase another 650,000 vials of bamlanivimab from the company for $812.5 million through January 31, 2021, under the contract through which the government bought an initial 300,000 vials over two months for $375 million—$1,250 a vial—to be provided by the Biomedical Advanced Research and Development Authority (BARDA) partnered with the DoD Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense and Army Contracting Command.

The contract is part of Operation Warp Speed, the Trump administration-launched program designed to accelerate the development, manufacturing, and distribution of COVID-19 vaccines, drugs, and diagnostics.

Bamlanivimab 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.