The National Institutes of Health (NIH) has started dosing patients in new trials of antibodies from GlaxoSmithKline/Vir Biotechnology and Brii Biosciences in patients hospitalized with COVID-19—hoping to succeed where Eli Lilly’s LY-CoV555 failed a few weeks ago.
The two sub-studies are part of the NIH’s ACTIV-3 program, an adaptive trial designed to push promising drugs quickly into testing as they become available, and should generate initial results early next year.
One sub-study is testing GSK and Vir’s fully human anti-SARS-CoV-2 antibody VIR-7831 (also known as GSK4182136), and the other will look at the combination of two Brii antibodies—BRII-196 and BRII-198.
Patients in the trial will be randomized to either placebo, VIR-7831 or the Brii duo, which will initially be tested in a group of 450 volunteers hospitalized with mild to moderate COVID-19 who have had symptoms for fewer than 13 days.
An initial readout will take place five days after dosing, looking at a range of factors including symptoms, how well subjects can manage daily activities and hard endpoints like the risk of death.
If that initial phase is positive, the two drug regimens will be tested against placebo in 700-patient studies that will also include patients with more severe COVID-19, with the endpoint sustained recovery for 14 days after release from the hospital, according to the NIH.
The investigators will be hoping for a better outcome than was seen in the ACTIV-3 sub-study of Lilly’s LY-CoV555, also known as bamlanivimab. That was abandoned in October after experts reviewed interim data on 326 patients and decided there was little chance that the antibody would have any clinical value in hospitalized COVID-19 patients.
Lilly said at the time it was possible LY-CoV555 may prevent the progression of earlier-stage COVID-19 patients who had been infected for a shorter time—the population that the NIH is recruiting in the GSK/Vir and Brii arms.
It also suggested that patients in the trial may have less benefit from neutralizing antibodies like LY-CoV555 and the new therapies under test as they “may have developed their own endogenous antibody response and be in a phase of disease characterized by inflammatory responses to virus,” and had received other treatment including Gilead’s antiviral Veklury (remdesivir).
Lilly’s drug received an emergency use authorization for the treatment of mild to moderate COVID-19 in adult and pediatric patients last month, and was joined shortly after by Regeneron’s antibody combination REGN-COV2.
GSK and Vir said they hoped VIR-7831’s “differentiating factors and broad anti-coronavirus activity” would allow it to succeed where Lilly’s drug failed.
They are also running a phase 2/3 trial of the drug called COMET-ICE that is trialing a single dose of the drug as a possible way to prevent hospitalization in COVID-19 patients, and they are planning a phase 3 trial to see whether the antibody can prevent symptomatic infection.
Beijing-headquartered Brii, meanwhile, said it is gearing up to start a trial of BRII-196 and BRII-198 in non-hospitalized COVID-19 patients who are at high risk of disease progression and is also planning a dedicated trial in Asian populations.