18 November 2021 - - US-based pharmaceutical company Pfizer Inc. (NYSE: PFE) has inked an agreement with the US government to supply 10 m treatment courses of its investigational COVID-19 oral antiviral candidate, Paxlovid (PF-07321332; ritonavir), subject to regulatory authorization from the US Food and Drug Administration, the company said.

If approved or authorized, Paxlovid, which originated in Pfizer's laboratories, would be the first oral antiviral of its kind, a 3CL protease inhibitor specifically designed to combat SARS-CoV-2.

Pfizer is seeking Emergency Use Authorization of Paxlovid with the US FDA; rolling submissions have also commenced in several countries, and the company will continue working to submit applications to regulatory agencies around the world.

Under the terms of the agreement, the US government will acquire 10m treatment courses to be delivered by Pfizer beginning later this year and concluding in 2022.

Pfizer will receive USD 5.29bn from the US government, pending and contingent upon regulatory authorization.

Pricing for Paxlovid is based on the principles of advance commitment, volume, equity, and affordability.

The price being paid by the US government is reflective of the high committed volume of treatment courses being purchased through 2022.

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.

PF-07321332 is designed to block the activity of the SARS-CoV-2-3CL protease, an enzyme that the coronavirus needs to replicate, at a stage known as proteolysis which occurs before viral RNA replication.

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

In preclinical studies, PF-07321332 did not demonstrate evidence of mutagenic DNA interactions.

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.

Pfizer is committed to working toward equitable access to Paxlovid for all people, aiming to deliver safe and effective antiviral therapeutics as soon as possible and at an affordable price.

If authorized or approved, during the pandemic, Pfizer will offer our investigational oral antiviral therapy through a tiered pricing approach based on the income level of each country to promote equity of access across the globe.

High and upper-middle income countries will pay more than lower income countries.

Pfizer has also begun and will continue to invest up to approximately USD 1bn of its own funds to support the manufacturing and distribution of this investigational treatment candidate, including exploring potential contract manufacturing options.

It has entered into advance purchase agreements with several countries and has initiated bilateral outreach to approximately 100 countries around the world.

Additionally, Pfizer has signed a voluntary licensing agreement with the Medicines Patent Pool to help expand access, pending regulatory authorization or approval, in 95 low- and middle-income countries that account for approximately 53% of the world's population.

In July 2021, Pfizer initiated the Phase 2/3 EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) randomized, double-blind study of non-hospitalized adult patients with COVID-19, who are at high risk of progressing to severe illness.

The primary analysis of the interim data set evaluated data from 1,219 adults who were enrolled by September 29, 2021.

At the time of the decision to stop recruiting patients, enrollment was at approximately 70% of the 3,000 planned patients from clinical trial sites across North and South America, Europe, Africa, and Asia, with 45% of patients located in the United States.

Enrolled individuals had a laboratory-confirmed diagnosis of SARS-CoV-2 infection within a five-day and were required to have at least one characteristic or underlying medical condition associated with an increased risk of developing severe illness from COVID-19.

Each patient was randomized to receive Paxlovid or placebo orally every 12 hours for five days.

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