Pfizer said several in vitro studies suggest that Paxlovid has the potential to maintain plasma concentrations many-fold times higher than the amount required to prevent Omicron from replicating in cells.
The studies analyzed the in vitro efficacy of nirmatrelvir, the active main protease (Mpro) inhibitor of Paxlovid, which is comprised of nirmatrelvir and ritonavir tablets.
In the first of these in vitro studies conducted by Pfizer, nirmatrelvir was tested against the Mpro — an enzyme that the coronavirus needs to replicate — from several SARS-CoV-2 variants of concern (VoCs), including Omicron, in a biochemical assay.
The results showed in all cases that nirmatrelvir was a potent inhibitor of its target. Nirmatrelvir’s Ki – a measure of its ability to bind to an enzyme – was approximately 1 nanomolar (nM) (or Ki fold change <1) for both the Omicron and the original Washington variant (USA-WA1/2020) in this assay, indicating its continued ability to prevent in vitro viral replication.
In a second in vitro study conducted by Pfizer, nirmatrelvir was tested against several SARS-CoV-2 VoCs, including Omicron, in an antiviral, cell-based assay. Reduction in viral load was measured through polymerase chain reaction (PCR) analysis, a test designed to detect the virus.
Nirmatrelvir’s EC50 — a measure of drug potency showing a concentration that is effective in producing 50% of the maximal response — was 16 nM for the Omicron variant, compared to 38 nM for the USA-WA1/2020 variant, reaffirming its robust in vitro antiviral activity.
An additional study, conducted by the Icahn School of Medicine at Mount Sinai (Icahn Mount Sinai) in collaboration with Pfizer, used a SARS-CoV-2-specific immunofluorescence-based assay to similarly detect the virus and measure the in vitro potency of nirmatrelvir, as well as some other authorized/approved COVID-19 therapeutics, against VoCs.
In this assay, treatments were tested against the Alpha, Beta, Delta, and Omicron variants in two cell lines. IC50 values — a measure of drug efficacy indicating the concentration needed to inhibit infection by half — ranging from 22 to 225 nM for nirmatrelvir compared to USA-WA1/2020, where the IC50 was 38 to 207 nM, were observed.
