Results from multiple studies show that the effectiveness of nirmatrelvir, the active main protease inhibitor of Paxlovid is maintained.
Pfizer has announced results from multiple studies showing that the in vitro efficacy of nirmatrelvir, the active main protease (Mpro) inhibitor of nirmatrelvir (PF-07321332) tablets and ritonavir tablets (Paxlovid), is maintained against the SARS-CoV-2 omicron variant.
The results of the in vitro studies show that Paxlovid has the potential to maintain plasma concentrations many-fold times higher than the amount required to prevent the omicron variant from replicating in cells.
“We specifically designed Paxlovid to retain its activity across coronaviruses, as well as current variants of concern with predominantly spike protein mutations.,” Mikael Dolsten, MD, PhD, chief scientific officer and president of worldwide research, development and medical at Pfizer, said in a statement.
“These data suggest that our oral COVID-19 therapy can be an important and effective tool in our continued battle against this devastating virus and current variants of concern, including the highly transmissible omicron. We will continue to monitor the treatment’s activity in real-world settings and believe that these in vitro findings will continue to be validated,” Dolsten said.
In the first of these in vitro studies, nirmatrelvir was tested against the Mpro, an enzyme that the coronavirus needs to replicate, from several SARS-CoV-2 variants of concern (VoCs), including the omicron variant, in a biochemical assay.
The results of the first study show that in all cases, 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 for both the omicron and the original Washington variant, indicating its ability to prevent in vitro viral replication.
In a second in vitro study, nirmatrelvir was tested against several SARS-CoV-2 VoCs, including the omicron variant, in an antiviral, cell-based assay. Reduction in viral load was measured through polymerase chain reaction 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 with 38 nM for the original Washington variant, which further confirmed nirmatrelvir’s in vitro antiviral activity.
These results are in line with the values observed in other VoCs, with EC50 measures ranging from 16 to 127 nM.
A additional study, conducted by the Icahn School of Medicine at Mount Sinai in collaboration with Pfizer, used a SARS-CoV-2-specific immunofluorescence-based assay to similar detect the virus and measure the in vitro potency of nirmatrelvir, as well as other approved and authorized COVID-19 therapeutics, against VoCs.
In this study, treatments were tested against the alpha, beta, delta, and omicron variants in 2 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 with 38 to 207 nM for the original Washington variant were observed.
The results from all 3 studies were submitted to bioRxiv, and the last 2 studies were submitted to peer-reviewed journals.
The findings are consistent with previous data made available to the public on December 28, 2021, and it provides confirmation for Pfizer’s findings that nirmatrelvir is the only orally administrable, authorized/approved compound, to date, that has been shown to have lower nanomolar in vitro activity against the omicron variant.
Previously, Pfizer announced final results from an analysis of a phase 2/3 trial of Paxlovid that showed the drug significantly reduced the risk of death or hospitalization from any cause by 89% compared with the placebo.
Pfizer shares in vitro efficacy of novel COVID-19 oral treatment against omicron variant. Pfizer. News release. January 18, 2022. Accessed January 18, 2022. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-shares-vitro-efficacy-novel-covid-19-oral-treatment