ACTIV-3, which is assessing LYCoV555, in combination with remdesivir, as a treatment for COVID-19 in hospitalized patients, the most advanced stage of the disease, is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).
To date, ACTIV-3 has enrolled 326 participants.
Participants in the trial are randomly assigned to receive either an intravenous infusion of LY-CoV555 or a saline placebo infusion, explained NIAID. All participants also receive standard care for patients hospitalized with COVID-19, including the antiviral remdesivir, it said. After five days, participants’ clinical status is assessed based on an ordinal scale. If LY-CoV555 appears to be safe and appears to be effective based on an evaluation of the first 300 participants (stage 1), an additional 700 participants are randomized and followed for 90 days to assess sustained recovery, defined as being discharged, alive and home for 14 days (stage 2), explained the institute.
NIAID said the DSMB noted yesterday morning that the trial reached a predefined boundary for safety at day five, meaning an overall difference in clinical status between the group receiving LY-CoV555 and the group receiving saline placebo.
"As a result, the DSMB recommended pausing enrollment out of an abundance of caution and continuing data collection and follow-up of current participants for safety and efficacy. The trial remains blinded to the investigators. The DSMB will review data again at a preplanned meeting on October 26. At that meeting, the DSMB will make a recommendation on whether or not enrollment should be resumed."
Lilly said it supports the decision taken by the monitoring board. “At this time, only the DSMB has reviewed the data from the trial, and NIH leadership and Lilly remain blinded to the ongoing trial results. Lilly trusts the judgment of the independent DSMB and supports its decisions to exercise caution in ensuring the safety of the patients participating in this study,” said the company today in a statement emailed to BioPharma-Reporter.
The drug maker said that individuals in the ACTIV-3 study have been infected with the virus for a longer period of time and may have more severe symptoms than patients studied in other bamlanivimab trials.
“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,” said the company.
It added that this is why the use of immunosuppressive treatments is both widespread and still being investigated in hospitalized patients.
Lilly said its other ongoing studies that are focused on earlier stages of COVID-19 disease or prophylaxis continue. “The DSMB also considered the impact of the ACTIV-3 study pause on ACTIV-2 and did not recommend any changes to that study’s design or enrollment.”
Emergency use authorization
LY-CoV555, a neutralizing IgG1 monoclonal antibody (mAb) directed against the spike protein of SARS-CoV-2, is designed to block viral attachment and entry into human cells, thus neutralizing the virus, potentially preventing and treating COVID-19. It is one of the first products of Lilly’s ongoing collaboration with Abcellera Biologics Inc.
Earlier this month, the company said that it was planning to seek emergency use authorization (EUA) from the US Food and Drug Administration (FDA) for the antibody in high-risk patients who have recently been diagnosed with mild-to-moderate COVID-19, based on previously disclosed findings for LY-CoV555.
Products based on mAb have been grabbing a lot of headlines of late in relation to COVID-19 treatment; last week saw Regeneron submit a request for EUA to the FDA for its REGN-COV2 investigational antibody combination for COVID-19 which was given to US President Donald Trump, as part of his treatment.
