According to Albert Bourla, Chairman and Chief Executive Officer, Pfizer, said that the “… authorization of Paxlovid represents another tremendous example of how science will help us ultimately defeat this pandemic, which, continues to disrupt and devastate lives across the world. This breakthrough therapy has been shown to significantly reduce hospitalizations and deaths and can be taken at home. It will change the way we treat COVID-19, and hopefully help reduce some of the significant pressures facing our healthcare and hospital systems.”

The FDA based its decision on clinical data from the Phase 2/3 EPIC-HR trial, which enrolled non-hospitalized adults aged 18 and older with confirmed COVID-19 who are at increased risk of progressing to severe illness. The data demonstrated an 89% reduction in the risk of COVID-19-related hospitalization or death from any cause in adults treated with Paxlovid, compared to placebo, within three days of symptom onset (primary endpoint).

No deaths occurred in the treatment group vs. nine deaths in the placebo group by Day 28. Similar results were seen in those treated within five days of symptom onset (secondary endpoint), with an 88% reduction in risk and no deaths observed in the treatment group.

Treatment-emergent adverse events were comparable between Paxlovid (23%) and placebo (24%), most of which were mild in intensity. While Paxlovid clinical trials did not include patients under the age of 18, the authorized adult dosing regimen is expected to result in comparable blood concentration levels of Paxlovid in pediatric patients 12 years of age and older weighing at least 40 kg.

Additional Phase 2/3 clinical trials are ongoing in adults at standard risk (i.e., low risk of hospitalization or death) of progressing to severe illness, and in those who have been exposed to the virus through household contacts.

With Paxlovid now authorized for emergency use, Pfizer stands ready to start delivery in the U.S. immediately.

In November 2021, Pfizer announced an agreement with the U.S. government to supply 10 million treatment courses of Paxlovid, with delivery fulfillment expected to be completed in 2022.

Paxlovid Outside of the U.S.

In addition to the U.S. FDA EUA, on December 16, 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued advice that Paxlovid can be used to treat adults with COVID-19 who do not require supplemental oxygen and who are at increased risk of progressing to severe disease. The EMA issued this advice under Article 5(3) of Regulation 726/2004 to support authorities of European Union (EU) Member States who may decide to allow the supply and use of Paxlovid, for example in emergency use settings, prior to EU conditional marketing authorization. 

Pfizer has submitted applications for regulatory approval or authorization to multiple regulatory agencies around the world and anticipates further regulatory decisions to follow. The company also plans to file a New Drug Application (NDA) with the FDA in 2022 for potential full regulatory approval.

Please see Full EUA Prescribing Information available at www.fda.gov and www.COVID19oralRx.com.

About the Pfizer Product PAXLOVID™ 

Paxlovid (nirmatrelvir [PF-07321332] tablets and ritonavir tablets) is a SARS-CoV-2 main protease (Mpro) inhibitor (also known as SARS-CoV2 3CL protease inhibitor) antiviral therapy. It was developed to be administered orally so that it can be prescribed at the first sign of infection or, pending clinical success of the rest of the EPIC development program and subject to regulatory authorization, at first awareness of an exposure – potentially helping patients avoid severe illness (which can lead to hospitalization and death) or avoid disease development following contact with a household member who contracts COVID-19. 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 inhibit the spike protein found on the surface of the SARS-CoV-2 virus, due to its high mutation rate. Paxlovid, however, works intracellularly by binding to the protease of the SARS-CoV-2 virus to inhibit viral replication.

Nirmatrelvir has shown consistent in vitro antiviral activity against current variants of concern (i.e., alpha, beta, delta, gamma, lambda, and mu). In addition, nirmatrelvir potently inhibited the Mpro associated with Omicron in an in vitro biochemical assay. This indicates nirmatrelvir’s potential to maintain robust antiviral activity against Omicron. Additional in vitro antiviral studies with this variant are underway.

Paxlovid is authorized to be administered at a dose of 300 mg (two 150 mg tablets) of nirmatrelvir with one 100 mg tablet of ritonavir, given 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.

All other secondary endpoints for this study are available on clinicaltrials.gov (NCT04960202), They were not yet available for this review. Full study data are expected to be released in the coming weeks.

Read about safety, tolerability, and interaction of Pfizer’s oral pills PAXLOVID™ by reading the entire firm’s press release at Pfizer’s website.

Emergency Use Authorization Statement

Paxlovid has not been approved, but has been authorized for emergency use by FDA under an EUA, for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS CoV-2 viral testing, and who are at high-risk for progression to severe COVID-19, including hospitalization or death.

The emergency use of Paxlovid is only authorized for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of drugs and biological products during the COVID-19 pandemic under Section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the declaration is terminated or authorization revoked sooner. 

Limitations of Authorized Use

• Paxlovid is not authorized for initiation of treatment in patients requiring hospitalization due to severe or critical COVID-19
• Paxlovid is not authorized for use as pre-exposure or post-exposure prophylaxis for prevention of COVID-19
  Paxlovid is not authorized for use for longer than 5 consecutive days
• Paxlovid may only be prescribed for an individual patient by physicians, advanced practice registered nurses, and physician assistants that are licensed or authorized under state law to prescribe drugs in the therapeutic class to which PAXLOVID belongs (i.e., anti-infectives).
• Paxlovid is not approved for any use, including for use for the treatment of COVID-19.
• Paxlovid is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of PAXLOVID under 564(b)(1) of the Food Drug and Cosmetic Act unless the authorization is terminated or revoked sooner.

For important safety information visit the Pfizer website.

There is more news from Pfizer and BioNTech (BNTX) that we will discuss in an upcoming post.

Prohost Observations 

We sincerely believe that the scientists will defeat COVID-19 and its variants. We hope that our beliefs are confirmed this holiday season.  

Happy Holidays Everyone!

We wish you good health and prosperity of positive feelings and happiness with love from all those who know you, and you them.

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