The National Institutes of Health (NIH) has scrapped a clinical trial of Eli Lilly’s anti-SARS-CoV-2 antibody in hospitalized COVID-19 patients. Investigators stopped enrolling patients in the study after finding LY-CoV555 is unlikely to improve outcomes in the studied patient population.
Earlier this month, the NIH paused enrollment in the clinical trial after the independent data safety monitoring board saw a difference in the clinical status between the cohorts that received LY-CoV555 and placebo. The difference crossed a predefined boundary for safety at Day 5. Yesterday, the board reviewed updated data on the 326 participants, leading it to advise the cessation of the trial.
The NIH said the recommendation was driven by “a low likelihood that the intervention would be of clinical value in this hospitalized patient population.” While safety was the trigger for the pause, the monitoring board saw no significant safety differences in the updated data set.
Exactly what happened in the trial, and whether it has implications for the wider LY-CoV555 program, will become clearer once data are published. The study of LY-CoV555, also known as bamlanivimab, in other patient populations is continuing. Lilly said it remains confident LY-CoV555 may prevent the progression of earlier-stage COVID-19 patients.
Lilly put forward a hypothesis for why LY-CoV555 may be ineffective in hospitalized patients when the NIH paused enrollment earlier this month. Hospitalized patients have been infected for longer, have more severe symptoms and receive different treatments such as Gilead Sciences' remdesivir, which was given in combination with LY-CoV555 to people in the treatment arm of the NIH study.
“For these reasons, hospitalized patients may have less benefit from neutralizing antibodies, which are a supplement to the patients’ own immune system, as they may have developed their own endogenous antibody response and be in a phase of disease characterized by inflammatory responses to virus,” Lilly wrote.
Patients covered by Lilly’s application for emergency use authorization (EUA) have different defining characteristics. Last month, Lilly shared early evidence, based on a small number of patients, that its antibody may reduce the rate of hospitalization in people with mild-to-moderate cases of COVID-19 at the time of treatment. Regeneron is also seeking an EUA for its antibody cocktail on the strength of early evidence REGN-COV2 may reduce viral levels and hospitalization rates in ambulatory patients.
Regeneron is still enrolling hospitalized COVID-19 patients in a study of REGN-COV2. That study is the most advanced ongoing evaluation of anti-SARS-CoV-2 antibodies in hospitalized patients, making it a critical test of whether the modality has a future in the treatment of people with advanced COVID-19.