Despite an NIH move to pause enrollment in a trial testing Eli Lilly and Co.'s COVID-19 antibody candidate, LY-CoV555, after a participant's unexplained illness, at least three other studies of the candidate remain underway, the company said Oct. 14. The paused trial, testing the antibody in hospitalized patients alongside the antiviral remdesivir, won't resume until Oct. 26, at the earliest.
Lilly said the ongoing studies include the phase II BLAZE-1 trial, testing LY-CoV555 as a monotherapy and in combination with LY-CoV016 in ambulatory care settings; the phase III BLAZE-2 trial, evaluating the potential of LY-CoV555 to prevent COVID-19 in residents and staff at long-term care facilities; and the NIH-sponsored trial ACTIV-2, testing LY-CoV555 in recently diagnosed COVID-19 patients with mild to moderate cases of the disease.
The paused NIH-sponsored trial, ACTIV-3, is designed to evaluate the efficacy of LY-CoV555 alongside the Gilead Sciences Inc. antiviral Veklury (remdesivir) in hospitalized COVID-19 patients. But Lilly cast doubt on the potential of the candidate for such patients today, noting in a statement that they "have been infected with the virus for a longer period of time and may have more severe symptoms” than patients studied in other trials of the antibody. Furthermore, the company said, "hospitalized patients receive different treatments for COVID-19 than earlier-stage patients.”
“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,” the company said. "This is why the use of immunosuppressive treatments is both widespread and still being investigated in hospitalized patients."
No further details of the illness that triggered the ACTIV-3 stop have emerged since Tuesday. But the NIH did share a little perspective on what happened: The data safety monitoring board (DSMB) for ACTIV-3 "noted 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," a spokeswoman for the National Institute of Allergy and Infectious Diseases told BioWorld.
"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," she said.
The trial has enrolled 326 out of a planned 10,000 participants to date, the NIH said. It remains blinded to the investigators. Next, the DSMB will review data again at a preplanned meeting on Oct. 26, at which point it will make a recommendation on whether or not enrollment should be resumed.