NEW YORK - Pfizer Inc. (NYSE: PFE) announced today that the U.S. Food and Drug Administration (FDA) approved PAXLOVID (nirmatrelvir tablets and ritonavir tablets) for the treatment of mild-to-moderate COVID-19 in adults who are at high risk for progression to severe COVID-19, including hospitalization or death.
PAXLOVID has been available in the U.S. since December 2021 under Emergency Use Authorization (EUA), and the overall benefit/risk profile and indication for use in eligible adults remain consistent with the EUA. More than 11.6 million treatment courses of PAXLOVID have been prescribed in the U.S. to date.1
'Great advancements have been made in the fight against COVID-19, yet the virus remains a present and unpredictable concern. This is especially true for the hundreds of millions of American adults who are age 50 or older or are otherwise at high risk for progression to severe illness, even if symptoms are initially mild,' said Albert Bourla, Chairman and Chief Executive Officer, Pfizer. 'Today marks a monumental milestone as PAXLOVID became the first COVID-19 oral treatment to be approved by the U.S. FDA, underscoring the value it brings to patients, providers, and health systems alike.'
COVID-19 continues to cause significant burden in the U.S. with approximately 14,500 reported cases each week as of the end of April 2023;2 but the majority of cases are not reported.3 In addition, data show that the impact of COVID-19 extends beyond an acute infection; an estimated 10-31 million Americans may experience persisting, recurring or new symptoms after the acute phase of COVID-19 infection.4,5
The FDA approval of PAXLOVID is based on the totality of scientific evidence shared by Pfizer, including safety and efficacy data from the EPIC (Evaluation of Protease Inhibition for COVID-19) clinical development program. This included results from the Phase 2/3 EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) study, which enrolled unvaccinated, non-hospitalized adults, aged 18 years and older, with confirmed COVID-19 who were at increased risk of progressing to severe disease. The data showed an 86% reduction in risk of COVID-19-related hospitalization or death from any cause through Day 28 in patients who initiated treatment with PAXLOVID within five days of symptoms onset, compared to placebo. The FDA approval was further supported by the results from a secondary endpoint of the Phase 2/3 EPIC-SR (Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients) study, which showed a numerical reduction in COVID-19-related hospitalizations or death from any cause through Day 28 in a sub-group of non-hospitalized adults, aged 18 years and older, with confirmed COVID-19 who had at least one risk factor for progression to severe disease and who were fully vaccinated. Available safety data have been consistent in participants across the EPIC clinical program, as well as across reported post-authorization safety experience in millions of patients prescribed PAXLOVID to date.
Recent real-world studies of PAXLOVID support the efficacy conclusions from Pfizer's EPIC clinical program, providing additional data on the use of PAXLOVID in the post-authorization setting of Omicron sub-lineage predominance and where high levels of pre-existing immunity occur. These real-world studies also have shown that PAXLOVID is effective amongst both vaccinated and unvaccinated high-risk patients.6,7,8,9,10
Based on the relative risk reduction seen across both clinical and real-world data, the FDA provided an estimate in March 2023 that more than 1,500 lives could be saved, and 13,000 hospitalizations avoided each week with PAXLOVID use in eligible patients.11
At this time, the U.S. government will continue to oversee the distribution of PAXLOVID, and U.S. residents eligible for PAXLOVID will continue to receive the medicine at no charge.
PAXLOVID remains available for eligible children, 12 to 17 years of age (and weighing at least 40 kg), under the existing EUA. Pfizer continues to gather pediatric data from the ongoing clinical trial, EPIC-Peds (Evaluation of Protease Inhibition for COVID-19 in Pediatric Patients) and intends to submit a supplemental New Drug Application (sNDA) to support the FDA approval of PAXLOVID in children at a future date.
PAXLOVID is currently approved or authorized for conditional or emergency use in more than 70 countries across the globe to treat COVID-19 patients who are at increased risk for progressing to severe illness.
About PAXLOVID (nirmatrelvir tablets and ritonavir tablets)
PAXLOVID is a SARS-CoV-2 main protease (Mpro) inhibitor (also known as SARS-CoV-2 3CL protease inhibitor) therapy. It was developed to be administered orally so that it can be prescribed early after infection, potentially helping patients avoid severe illness (which can lead to hospitalization and death). Nirmatrelvir, which originated in Pfizer laboratories, is designed to block the activity of the Mpro, an enzyme that the coronavirus needs to replicate. Co-administration with a low dose of ritonavir helps slow the metabolism, or breakdown, of nirmatrelvir in order for it to remain active in the body for longer periods of time at higher concentrations to help combat the virus.
Nirmatrelvir is designed to inhibit viral replication at a stage known as proteolysis, which occurs before viral RNA replication. In preclinical studies, nirmatrelvir did not demonstrate evidence of mutagenic DNA interactions.
Current variants of concern 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 (3CL protease) of the SARS-CoV-2 virus to inhibit viral replication. Nirmatrelvir has consistently shown in vitro antiviral activity against the variants Alpha, Beta, Delta, Gamma, Lambda, Mu, and Omicron BA.1, BA.2, BA.2.12.1, BA.4, BA.4.6, BA.5, BF.7, BQ.1.11, BQ.1 and XBB.1.5. Work is ongoing to evaluate activity against recently identified variants as they become available for testing.
PAXLOVID is generally administered at a standard dose of 300 mg (two 150 mg tablets) of nirmatrelvir with one 100 mg tablet of ritonavir, given twice-daily for five days. One standard dose carton contains blister packs of PAXLOVID, as co-packaged nirmatrelvir tablets with ritonavir tablets, providing all required doses for a full five-day treatment course. The modified dose for patients with moderate renal impairment (eGFR 30 to
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