Pfizer announced that the U.S. FDA has approved an Emergency Authorization Application (EUA) for its novel COVID-19 oral antiviral candidate Paxlovid for the treatment of COVID-19 infections in non-hospitalized adults at high risk of developing serious illness.
Paxlovid is a combination of nirmatrelvir, a 3CL protease inhibitor, and low-dose ritonavir (Ritonavir), which consists of a combination of 300 mg (two 150 mg tablets) of nirmatrelvir and one 100 mg tablet of ritonavir administered orally to patients with new crowns twice daily for 5 days. Ritonavir helps to slow down the metabolism or breakdown of nirmatrelvir so that its effective concentration in the body is maintained for a longer period of time, resulting in sustained antiviral activity.
Effective 89% for Omicron variant
Pfizer announced on November 5 the results of an interim analysis of a randomized, double-blind, Phase II/III EPIC-HR study of Paxlovid for the treatment of non-hospitalized, high-risk adult COVID-19-infected patients with the risk of developing a serious illness. The data showed that among patients treated within three days of symptom onset, Paxlovid reduced the risk of COVID-19-related hospitalization or death from any cause by 89% compared to placebo (primary endpoint). Similar reductions in COVID-19-related hospitalization or death were seen among patients treated within five days of symptom onset.
On December 15, Pfizer announced results from the final analysis of the EPIC-HR study, which were consistent with the interim analysis announced in November 2021, that among patients treated within three days of symptom onset, Paxlovid reduced the risk of COVID-19-related hospitalization or death from any cause by 89% compared to placebo.
For the secondary endpoint, among patients treated within five days of symptom onset, Paxlovid reduced the risk of COVID-19-related hospitalization or death from any cause by 88% compared to placebo, up from 85% observed in the interim analysis.
Results of a SARS-CoV-2 viral load assay in 499 patients in the EPIC-HR trial showed an approximately 10-fold reduction in viral load at Day 5 relative to baseline in patients in the Paxlovid arm relative to placebo, suggesting that Paxlovid has potent activity against SARS-CoV-2, and is the most potent of the oral COVID-19 formulations reported to date the strongest viral load reduction.
In addition, recent in vitro data confirm that nirmatrelvir is a potent inhibitor of the omicron 3CL protease. Combined with the available in vitro antiviral and protease inhibition data for other Variants of Concern (VoC), including Delta, this suggests that Paxlovid will maintain potent antiviral activity against VoC as well as other coronavirus variants!
Licensees can supply to 95 countries
On the same day that Pfizer submitted its emergency authorization application for Paxlovid to the FDA, it entered into an agreement with the Medicines Patent Pool (MPP) that will allow additional manufacturers to produce nirmatrelvir.
Pfizer, in a statement on its collaboration with the MPP, cited that the agreement will enable the MPP to facilitate additional production and distribution of nirmatrelvir through the award of sublicenses to qualified generic manufacturers to facilitate additional production and distribution of investigational antivirals, pending regulatory authorization or approval, with the aim of facilitating greater access to the global population.
Under the terms of the license agreement between Pfizer and the MPP, qualified generic companies that have been granted a sublicense globally will be able to offer the combination therapy of nirmatrelvir and ritonavir to 95 countries, covering approximately 53 percent of the global population, including all low- and lower-middle-income countries and a number of upper-middle-income countries in sub-Saharan Africa, as well as those that have transitioned from lower-middle- to upper-middle-income status in the past five years. status to upper-middle-income status in the past five years.
With COVID-19 still classified as a public health emergency of international concern by the World Health Organization, Pfizer will not charge royalties on sales to low-income countries and will further waive royalties on sales in all countries covered by the agreement.
Pfizer is committed to developing scientifically groundbreaking therapies to help end this epidemic for all,” said Albert Bourla, Pfizer’s chairman and chief executive officer. We believe oral antiviral therapy can play an important role in reducing the severity of COVID-19 infections, easing the strain on healthcare systems and saving lives. We must work to ensure that the benefits of these breakthrough therapies are available to all, and we are pleased to partner with MPP to further advance our commitment to healthcare equity.”
Merck Sharp & Dohme molnupiravir Receives 13:10 Vote of Support from FDA Expert Committee
On November 14, Merck Sharp & Dohme/Ridgeback announced that the Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing approval in the United Kingdom for molnupiravir (MK-4482, EIDD-2801) for the treatment of mild to moderate COVID-19 adult patients.
Molnupiravir is the first oral antiviral drug approved globally for the treatment of adults with mild-to-moderate COVID-19 who have tested positive for the SARS-CoV-2 diagnostic test and have at least one risk factor for developing serious disease. In October of this year, Merck Sharp & Dohme struck a similar deal with MPP, agreeing to allow other drugmakers to manufacture molnupiravir in 105 poorer countries.
On November 30, the FDA’s Antimicrobial Drugs Advisory Committee (AMDAC) voted 13 in favor and 10 against the Emergency Use Authorization (EUA) application for molnupiravir, giving it Positive Support.
The Advisory Committee concluded that the known and potential benefits outweigh the unknown and potential risks for adult patients at high risk for mild-to-moderate COVID-19 treated with molnupiravir within 5 days of symptom onset.
Merck Sharp & Dohme’s EUA filing is based primarily on positive results from the interim analysis of the Phase III MOVe-OUT study, as well as recently updated data. Results from the interim analysis showed that molnupiravir reduced the risk of hospitalization and death by 50%. data from the full analysis, which was conducted on November 26 for all subjects (n=1433), showed that molnupiravir reduced the risk of hospitalization or death by 30% (HR: 0.70). As for the reasons for this result of decreased efficacy, Merck Sharp & Dohme has no plausible explanation at this time