Pfizer’s Novel COVID-19 Oral Treatment Demonstrates In Vitro Efficacy Against Omicron Variant
By HospiMedica International staff writers Posted on 20 Jan 2022 |
Pfizer Inc. (New York, NY, USA) has shared the results from multiple studies demonstrating that the in vitro efficacy of nirmatrelvir, the active main protease (Mpro) inhibitor of PAXLOVID (nirmatrelvir [PF-07321332] tablets and ritonavir tablets), is maintained against the SARS-CoV-2 variant Omicron.
Taken together, these 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. 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.
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. These results are in line with the values that have been observed for other VoCs (Alpha, Beta, Gamma, Delta, Lambda, and Mu) in this assay.
An additional study conducted by 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.
These findings provide confirmation to Pfizer’s findings that nirmatrelvir is the only orally administrable, authorized/approved compound which, to date, has been shown to have low nanomolar in vitro activity against Omicron. Current VoCs can be resistant to treatments that work by binding to the spike protein found on the surface of the SARS-CoV-2 virus. PAXLOVID, however, works intracellularly by binding to the highly conserved Mpro of the SARS-CoV-2 virus. Previous data have also indicated that PAXLOVID maintains in vitro efficacy against earlier and current VoCs, including Alpha, Beta, Gamma, Delta, Lambda, and Mu. PAXLOVID is currently authorized for conditional or emergency use in several countries across the globe. Pfizer has submitted applications for regulatory approval or authorization to multiple regulatory agencies and anticipates further regulatory decisions to follow.
“We specifically designed PAXLOVID to retain its activity across coronaviruses, as well as current variants of concern with predominantly spike protein mutations. Following the clinical findings - showing PAXLOVID reduced risk of hospitalization or death by nearly 90% compared to placebo for high-risk patients when treated within five days of symptom onset - we are encouraged by these initial laboratory findings,” said Mikael Dolsten, M.D., Ph.D., Chief Scientific Officer and President, Worldwide Research, Development and Medical of Pfizer. “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.”
Related Links:
Pfizer Inc.
Latest COVID-19 News
- Low-Cost System Detects SARS-CoV-2 Virus in Hospital Air Using High-Tech Bubbles
- World's First Inhalable COVID-19 Vaccine Approved in China
- COVID-19 Vaccine Patch Fights SARS-CoV-2 Variants Better than Needles
- Blood Viscosity Testing Can Predict Risk of Death in Hospitalized COVID-19 Patients
- ‘Covid Computer’ Uses AI to Detect COVID-19 from Chest CT Scans
- MRI Lung-Imaging Technique Shows Cause of Long-COVID Symptoms
- Chest CT Scans of COVID-19 Patients Could Help Distinguish Between SARS-CoV-2 Variants
- Specialized MRI Detects Lung Abnormalities in Non-Hospitalized Long COVID Patients
- AI Algorithm Identifies Hospitalized Patients at Highest Risk of Dying From COVID-19
- Sweat Sensor Detects Key Biomarkers That Provide Early Warning of COVID-19 and Flu
- Study Assesses Impact of COVID-19 on Ventilation/Perfusion Scintigraphy
- CT Imaging Study Finds Vaccination Reduces Risk of COVID-19 Associated Pulmonary Embolism
- Third Day in Hospital a ‘Tipping Point’ in Severity of COVID-19 Pneumonia
- Longer Interval Between COVID-19 Vaccines Generates Up to Nine Times as Many Antibodies
- AI Model for Monitoring COVID-19 Predicts Mortality Within First 30 Days of Admission
- AI Predicts COVID Prognosis at Near-Expert Level Based Off CT Scans