EUA for Lilly, AbCellera COVID mAb despite Phase II miss for authorized dose
FDA’s first emergency use authorization for a SARS-CoV-2-targeting mAb covers the lowest dose of Lilly and AbCellera’s candidate to treat COVID-19 outpatients, a dose that was not effective in the Phase II BLAZE-1 trial in the indication.
The agency said the EUA was based on interim data from the BLAZE-1 trial in which the middle, 2,800 mg, dose of bamlanivimab — but not the authorized dose of 700 mg or the high dose of 7,000 mg — met the primary endpoint of lowering baseline viral loads at day 11 vs. placebo.
The results were published Oct. 28 in The New England Journal of Medicine.
On Sept. 16, when Lilly first announced preliminary results, VP of Immunology Ajay Nirula told BioCentury that nasopharyngeal levels of SARS-CoV-2 at day 11 weren’t particularly meaningful because, by that point, most patients in all cohorts, including the placebo groups, had low or undetectable levels. Nirula’s conclusion then was that earlier timepoints would more meaningfully represent the therapy’s effect.
Additional data reported by Lilly on Oct. 7 showed viral loads were not significantly lower at days three or seven in prespecified analyses of pooled data from the three bamlanivimab groups.
The earlier results did suggest, however, that the mAb decreased ER visits and hospitalization rates, producing a statistically significant effect on the combined metric in the pooled treatment arms vs. placebo (1.6% vs. 5.8%, p=0.02). In addition, the low, medium and high doses of bamlanivimab significantly lowered symptom scores on a 24-point scale over 11 days, relative to placebo (-7.9, p=0.009; -6.35, p=0.038; and -7.86, p=0.011, respectively).
Although the 700 mg monotherapy dose did not meet BLAZE-1’s primary endpoint, Eli Lilly and Co. (NYSE:LLY) CSO Daniel Skovronsky said on an Oct. 7 conference call to discuss the data that there were no differences between the three monotherapy doses on the viral, symptom or hospitalization endpoints.
He added that the company believed it had not yet found the lowest effective dose, and that Lilly planned to test lower doses that, if effective, could further stretch supply.
The EUA covers patients ages 12 and older weighing at least 40 kg with mild to moderate COVID-19 who have been symptomatic for ≤10 days and are at high risk of progressing to severe disease or hospitalization.
The U.S. government, which will control the neutralizing mAb’s distribution, has purchased 300,000 doses and will make weekly allocation decisions proportional to the previous seven days’ confirmed COVID-19 cases in each state and territory.
AmerisourceBergen will distribute the vaccine, and it will be up to states and territories to determine where it will be administered.
Lilly anticipates manufacturing up to one million 700 mg bamlanivimab doses by year-end for global use through early 2021, and expects to bring additional manufacturing capacity online beginning 1Q21.
Supply constraints have shadowed the anticipated EUA for bamlanivimab, as well as for the two-mAb cocktail REGN-COV2 from Regeneron Pharmaceuticals Inc. (NASDAQ:REGN). In early October, former FDA commissioners Scott Gottlieb and Mark McClellan projected that demand in the U.S. for COVID-19 mAbs could exceed 12,000 doses per day.