The target Prescription Drug User Fee Act (PDUFA) action date for a decision by the FDA is May 2023
Pfizer Inc. (NYSE: PFE) announced today that the U.S. Food and Drug Administration’s (FDA) Antimicrobial Drugs Advisory Committee (AMDAC) voted 16 to 1 that available data support the safety and effectiveness of PAXLOVID™ (nirmatrelvir tablets and ritonavir tablets) for the treatment of mild-to-moderate COVID-19 in adult patients who are at high risk for progression to severe illness. The AMDAC’s vote, while not binding, will be considered by the FDA when making its decision regarding the potential approval of PAXLOVID.
“We believe it is critical for adults who are at high risk of progression to severe COVID-19 to have access to safe and effective treatment options, like PAXLOVID, to help prevent avoidable hospitalizations and deaths,” said James Rusnak, Senior Vice President and Chief Development Officer, Internal Medicine, Anti-infectives and Hospital, Pfizer. “We are encouraged by the AMDAC’s positive vote today. The outcome is well supported by the strong safety and efficacy data seen both in our clinical trials and in a growing base of real-world evidence, showing that PAXLOVID helps to reduce the risk of hospitalization or death for high-risk adult patients regardless of vaccination status.”
The AMDAC based its vote on the totality of scientific and real-world 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 study (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients), which enrolled unvaccinated, non-hospitalized adults, aged 18 years and older, with confirmed COVID-19 who are 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 treated with PAXLOVID within 5 days of symptoms onset, compared to placebo. The vote was further supported by results from a secondary endpoint of the Phase 2/3 EPIC-SR study (Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients) which showed the effectiveness of Paxlovid 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.
In addition, real-world evidence presented to the AMDAC showed that PAXLOVID’s clinical profile in the post-authorization setting is consistent with the safety and efficacy conclusions from the EPIC clinical program, including observations made when the Omicron variant and its lineages were the predominant forms of SARS-CoV-2 in circulation. This real-world evidence also shows the effectiveness of PAXLOVID among vaccinated patients and patients who developed natural immunity.1,2,3
COVID-19 continues to cause significant burden in the U.S. as case rates fluctuate and new variants and sub-variants emerge, regardless of virulence. Approximately 4,000‒5,000 hospital admissions and 500‒600 deaths are caused by the virus each day in the U.S., as of January 2023.4 With more than 200 million adults in the U.S. at high risk of severe COVID-19, there is a critical need for treatment options in this population.5 According to the U.S. Centers for Disease Control and Prevention (CDC), factors which could put someone at high risk of severe COVID-19 include any of the following: being aged 50 and older, obesity, diabetes (type 1 and type 2), heart conditions, smoking (current or former), physical inactivity, chronic kidney or liver disease, and cancer, among others.6
If approved by the FDA, PAXLOVID could be the first U.S. FDA-approved oral treatment for COVID-19. The target Prescription Drug User Fee Act (PDUFA) action date for a decision by the FDA is May 2023. Under the FDA emergency use authorization (EUA), PAXLOVID is currently authorized for use in, and remains available to, adults and pediatric patients (12 years of age and older weighing at least 40 kg) at high risk of progression to severe COVID-19. In the U.S., more than 10 million treatment courses of PAXLOVID have been prescribed to date.7
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 (NDA) to support the FDA approval of PAXLOVID in children at a future date. In February 2023, the European Commission (EC) granted standard Marketing Authorization (MA) of PAXLOVID for the treatment of COVID-19 in adults who do not require supplemental oxygen and who are at increased risk of the disease becoming severe.
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 shown consistent 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, taken together twice-daily for five days. One carton contains five blister packs of PAXLOVID, as co-packaged nirmatrelvir tablets with ritonavir tablets, providing all required doses for a full five-day treatment course. The dose for patients with moderate renal impairment (eGFR ≥30 to <60 mL/min) should be reduced to 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet), with both tablets taken together twice daily for five days (PAXLOVID is not recommended in patients with severe renal impairment [eGFR <30 mL/min]).
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