Vaccine Info

PAXLOVID Oral Antiviral (PF-07321332)

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December 7, 2021
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PAXLOVID Oral Antiviral (PF-07321332) Description

Pfizer's PAXLOVID™ PF-07321332 is an oral antiviral therapeutic targeting the SARS-CoV-2 betacoronavirus to prevent COVID-19. PAXLOVID is a protease inhibitor that has demonstrated potent in vitro antiviral activity against SARS-CoV-2 and other coronaviruses, suggesting potential for use in the treatment of COVID-19, as well as potential use against future virus threats, says Pfizer.

By inhibiting the main protease, PF-07321332 prevents the virus from cleaving long protein chains into the parts it needs to reproduce itself. Thus, PF-07321332 is the first orally administered coronavirus-specific investigational protease inhibitor to be evaluated in phase 3 clinical studies.

Protease inhibitors bind to a viral enzyme (protease), preventing the virus from replicating in the cell. Protease inhibitors have effectively treated other viral pathogens such as HIV and hepatitis C virus alone and other antivirals. 

There is no orally administered therapy currently approved for the post-exposure or pre-emptive treatment of COVID-19, says Pfizer. Therefore, Pfizer is also investigating an intravenously administered investigational protease inhibitor, PF-07304814, which is currently in Phase 1b multi-dose trial in hospitalized clinical trial participants with COVID-19.

Co-administration with a low dose of ritonavir helps slow the metabolism, or breakdown of (PF-07321332), to remain active in the body for more extended periods at higher concentrations to help combat the virus.

PAXLOVID (PF-07321332) inhibits viral replication at a stage known as proteolysis, which occurs before viral RNA replication. It is an analog of GC373, where the aldehyde covalent cysteine acceptor replaced a nitrile. In this combination, ritonavir serves to slow down the metabolism of PF-07321332 by cytochrome enzymes to maintain higher circulating concentrations of the primary drug. In preclinical studies, PF-07321332 did not demonstrate evidence of mutagenic DNA interactions.

Pfizer Inc. announced on November 5, 2021, findings from a randomized, double-blind study of non-hospitalized adult patients with COVID-19, who are at high risk of progressing to severe illness, the interim analysis showed an 89% reduction in risk of COVID-19-related hospitalization or death from any cause compared to placebo in patients treated within three days of symptom onset.

On November 19, 2021, the European Medicines Agency announced preliminary results indicating that Paxlovid reduced the risk of hospitalization or death compared with placebo when treatment was given within 3 or 5 days of the start of symptoms.

Chemical Formula: C23H32F3N5O4; DrugBank Accession Number DB16691; CAS Number 2628280-40-8; PubChem CID 155903259; Molecular Weight: 499.5

To learn more, please visit New York-based Pfizer Inc. at www.Pfizer.com. (NYSE: PFE).

PAXLOVID Oral Antiviral (PF-07321332) History

Pfizer developed PF-07321332 by modification of PF-07304814 (Lufotrelvir), which is also a covalent inhibitor. PF-07304814 needs to be administered intravenously, not orally. PF-07321332 is also a covalent inhibitor, but its warhead is a phosphate prodrug of a hydroxyketone.

A scheduled interim analysis announced on November 5, 2021, showed an 89% reduction in risk of COVID-19-related hospitalization or death from any cause compared to placebo in patients treated within three days of symptom onset; 0.8% of patients who received PAXLOVID™ were hospitalized through Day 28 following randomization, compared to 7.0% of patients who received placebo and were hospitalized or died.

PAXLOVID Oral Antiviral (PF-07321332) Indication

PAXLOVID (PF-07321332) oral antiviral therapy is indicated to prevent the SARS-CoV-2 virus from replicating in human host cells. If successful, PF-07321332 can be prescribed to patients before they require hospitalization. Protease inhibitors, like PF-07321332, are designed to block the activity of the main protease enzyme that the coronavirus needs to replicate.

If authorized or approved, PAXLOVID would be the first oral antiviral of its kind, a 3CL protease inhibitor specifically designed to combat SARS-CoV-2 that could be prescribed as an at-home treatment to high-risk patients at the first sign of infection, potentially helping patients avoid severe illness, which can lead to hospitalization and death.

PAXLOVID Oral Antiviral (PF-07321332) Distribution

Under the terms of the head license agreement between Pfizer and MPP, announced on November 16, 2021, qualified generic medicine manufacturers worldwide that are granted sub-licenses will be able to supply PF-07321332 in combination with ritonavir to 95 countries, covering up to approximately 53% of the world's population. This agreement includes all low- and lower-middle-income countries and some upper-middle-income countries in Sub-Saharan Africa, as well as countries that have transitioned from lower-middle to upper-middle-income status in the past five years.

PAXLOVID Oral Antiviral (PF-07321332) Dosage

If authorized or approved, PAXLOVID will be administered at a dose of 300mg (two 150mg tablets) of PF-07321332 with one 100mg tablet of ritonavir, given twice daily for five days.

PAXLOVID Oral Antiviral (PF-07321332) Price

Pfizer Inc. sold PAXLOVID to the U.S. government for $529 per course.

PAXLOVID Oral Antiviral (PF-07321332) Revenues

Pfizer Inc. announced a potential PAXLOVID sale of $5.29 billion to be recognized as revenue in 2021 and 2022. The company recently raised Full-Year 2021 Guidance for Revenues to a Range of $81.0 to $82.0 Billion.

PAXLOVID Oral Antiviral (PF-07321332) News

December 7, 2021 - CNBC's Meg Tirrell tweeted 'Pfizer CEO says he expects Paxlovid to be available this year. He says FDA would like to see final data from Pfizer's study, noting Merck's final numbers "created a change."

December 3, 2021 - Filomena Tassi, Canada's minister of public services and procurement, told reporters the government has signed agreements with Pfizer Inc. to buy up to 1 million courses of PF-07321332.

November 30, 2021 - Pfizer's CEO @AlbertBourla Tweeted 'if authorized, we're confident our oral antiviral therapy can help reduce the severity of illness, and we now anticipate we can deliver 80M treatment courses, up from our original estimate of 50M.'

November 29, 2021 - CNBC reported Pfizer estimates it can manufacture 80M treatment courses of Paxlovid, up from 50M projected a few weeks ago.

November 19, 2021 - The EMA announced it is reviewing currently available data on the use of Paxlovid to support national authorities who may decide on its use in emergency use settings, prior to marketing authorization. 

November 18, 2021 - Pfizer Inc. announced an agreement with the U.S. government to supply 10 million treatment courses of PAXLOVID™ (PF-07321332; ritonavir), subject to regulatory authorization beginning later this year and concluding in 2022. Under the terms of the agreement, Pfizer will receive $5.29 billion from the U.S. government. Pricing for PAXLOVID is based on the principles of advance commitment, volume, equity, and affordability. The company has also entered into advance purchase agreements with several other countries and has initiated bilateral outreach to approximately 100 countries around the world.

November 16, 2021 - Pfizer Inc. announced it is seeking Emergency Use Authorization of its investigational oral antiviral candidate, PAXLOVID™ (PF-07321332; ritonavir), for the treatment of mild to moderate COVID-19 in patients at increased risk of hospitalizations or death. Rolling submission of non-clinical data for PAXLOVID was initiated with the U.S. FDA in October 2021.

November 16, 2021 - Pfizer Inc. and the Medicines Patent Pool announced the signing of a voluntary license agreement for Pfizer's COVID-19 oral antiviral treatment candidate PF-07321332, which is administered in combination with low dose ritonavir (PF-07321332; ritonavir). The agreement will enable MPP to facilitate additional production and distribution of the investigational antiviral, pending regulatory authorization or approval, by granting sub-licenses to qualified generic medicine manufacturers to facilitate greater access to the global population.

November 13, 2021 - i24News reported an agreement with Pfizer has been reached. The Paxlovid shipment will be despatched as soon as Pfizer receives U.S. FDA approval.

November 10, 2021 - The journal Nature published an article: COVID antiviral pills: what scientists still want to know.

November 8, 2021 - The BMJ published an article: Commenting on the PAXLOVID announcement, England's health and social care secretary, Sajid Javid, said, "If approved, this could be another significant weapon in our armory to fight the virus alongside our vaccines and other treatments, including molnupiravir, which the UK was the first country in the world to approve this week."

November 5, 2021 - Pfizer Inc. announced its investigational novel COVID-19 oral antiviral candidate, PAXLOVID™, significantly reduced hospitalization and death, based on an interim analysis of the Phase 2/3 EPIC-HR randomized, double-blind study of non-hospitalized adult patients with COVID-19, who are at high risk of progressing to severe illness. The scheduled interim analysis showed an 89% reduction in risk of COVID-19-related hospitalization or death from any cause compared to placebo in patients treated within three days of symptom onset (primary endpoint); 0.8% of patients who received PAXLOVID™ were hospitalized through Day 28 following randomization (3/389 hospitalized with no deaths), compared to 7.0% of patients who received placebo and were hospitalized or died (27/385 hospitalized with seven subsequent deaths). The statistical significance of these results was high (p<0.0001). Similar reductions in COVID-19-related hospitalization or death were observed in patients treated within five days of symptom onset; 1.0% of patients who received PAXLOVID™ were hospitalized through Day 28 following randomization (6/607 hospitalized, with no deaths), compared to 6.7% of patients who received a placebo (41/612 hospitalized with ten subsequent deaths), with high statistical significance (p<0.0001). In addition, in the overall study population through Day 28, no casualties were reported in patients who received PAXLOVID™ as compared to 10 (1.6%) deaths in patients who received placebo.

October 5, 2021 - Australia announced the TGA had granted provisional determination to Pfizer Australia concerning a new combination medicine containing PF-07321332 and ritonavir to treat adult patients with symptomatic, confirmed coronavirus infection. The granting of a provisional determination means that the TGA has decided that Pfizer Australia is now eligible to apply for provisional registration of this treatment in the Australian Register of Therapeutic Goods.

September 27, 2021 - Pfizer Inc. announced the start of the Phase 2/3 EPIC-PEP study to evaluate the investigational novel oral antiviral candidate PF-07321332, co-administered with a low dose of ritonavir, for the prevention of COVID-19 infection. This Phase 2/3 trial is part of a global clinical research program. It enrolls individuals at least 18 years old and who live in the same household as an individual with a confirmed symptomatic SARS-CoV-2 infection.

September 1, 2021 - Pfizer Inc. shared that the first participant has been dosed in a pivotal Phase 2/3 clinical trial to evaluate the safety and efficacy of PF-07321332 – an investigational orally administered protease inhibitor antiviral therapy designed specifically to combat COVID-19 – in non-hospitalized, symptomatic adult participants who have a confirmed diagnosis of SARS-CoV-2 virus infection and are not at increased risk of progressing to severe illness, which may lead to hospitalization or death. 

July 28, 2021 - Pfizer today provided further details on its oral protease inhibitor program for the treatment of COVID-19. PF-07321332 exhibits potent, selective in vitro antiviral activity against SARS-CoV-2 and other coronaviruses. Additionally, it has demonstrated robust preclinical antiviral effects in human cells in vitro and SARS-CoV-2 infected animals. In Phase 1 pharmacokinetic study in healthy volunteers, PF-07321332 has shown high drug exposure over ten days, - 12 - exceeding the level of exposure predicted to inhibit SARS-CoV-2 viral replication by more than five-fold. Based on these data, Pfizer initiated a Phase 2/3 trial in COVID-19 patients in July 2021. Data from the trial are expected in the fourth quarter of 2021.

May 4, 2021 - Pfizer Inc. published today its 'Key Near-term Potential Milestones for COVID-19 Vaccine Program (2021)' on slide #8 within its financial report.

April 7, 2021 - Chemical & Engineering News published: Pfizer unveils its oral SARS-CoV-2 inhibitor.

March 23, 2021 - Pfizer Inc. announced that it is progressing to multiple ascending doses after completing the dosing of single ascending doses in a Phase 1 study in healthy adults to evaluate the safety and tolerability of an investigational, novel oral antiviral therapy for SARS-CoV-2, the virus that causes COVID-19. This Phase 1 trial is being conducted in the United States.

PAXLOVID PF-07321332 Protease Inhibitor Antiviral Clinical Trials

A Phase 1, double-blind, sponsor open, single, and multiple ascending dose study evaluates the safety, tolerability, and pharmacokinetics of PF-07321332 in healthy participants.

ClinicalTrials.gov Identifier: NCT04960202 - The purpose of this Phase 2/3 study is to determine whether PF-07321332/ritonavir is safe and effective for the treatment of adults who are ill with COVID-19 and do not need to be in the hospital but are at an increased risk of developing severe illness. A provision will be made throughout the study period to allow study visits to be conducted at a participant's home or another non-clinic location if available. The total study duration is up to 24 weeks. Estimated Primary Completion Date: October 5, 2021. Last update date: September 1, 2021.

The Phase 2/3 EPIC-PEP trial is a randomized, double-blind, placebo-controlled study and will enroll up to 2,660 healthy adult participants aged 18 and older. Participants will be randomly assigned (1:1:1) to receive PF-07321332/ritonavir or placebo orally twice daily for 5 or 10 days. The primary objective will assess safety and efficacy to prevent confirmed SARS-CoV-2 infection and its symptoms through Day 14. PF-07321332 is an oral antiviral SARS-CoV-2-3CL protease inhibitor, which has an encouraging preclinical profile, including potent in vitro antiviral SARS-CoV-2 and broad coronavirus activity. Results from the Phase 1 clinical trial demonstrated that PF-07321332 was safe and well-tolerated.

For more information on the EPIC Phase 2/3 clinical trials for PAXLOVID, visit clinicaltrials.gov.

Clinical Trials

No clinical trials found