A team of pharmacists and physicians at Michigan Medicine set out to determine whether mutations in SARS-CoV-2 could decrease the effectiveness of monoclonal antibodies. To answer this question, they used data pulled from ongoing genetic sequencing of the virus from actual patients.
In their paper, they detail their experience using the three primary monoclonal antibodies therapies: bamlanivimab (BAM), casirivimab plus imdevimab (CAS-IMD), and bamlanivimab plus etesevimab (BAM-ETE). The U.S. Food and Drug Administration (FDA) granted emergency use authorization for these therapies for people with mild to moderate COVID-19 who are at risk of developing severe disease.
“What was starting to be alarming was that there was this question of possible immune evasion and concern with reinfection or vaccine efficacy,” said Jason Pogue, PharmD, of the University of Michigan College of Pharmacy.
Some of the earlier identified variants of concern with a combination of mutations, like the Beta (B.1.351) and Gamma (P.1) variants, rendered BAM, CAS, and ETE ineffective. “The good news is the [CAS-IMD] combo is still active against these variants,” said Pogue.
“We are fortunate enough to have a good handle on what the local virus looks like, take that information in real time and, based off the percentage of those two variants that compromise BAM-ETE, we would decide whether we needed to shift all the way over to CAS-IMD or if we could still use both available monoclonal antibody combinations,” said Pogue.
This calculation was important because of the uncertainty around the continued spread of COVID-19 and drug availability. The Michigan Medicine team decided, in a move that has since been followed at the state level, that once a variant that impacted a therapy reached 10% of all cases, they would recommend switching therapies.
“That’s actually what’s happening at the state level in eight states where data says there is greater than 10 percent of these variants—they’ve stopped distributing BAM-ETE,” noted Pogue.
