If approved or authorized, PAXLOVID™ (PF-07321332; ritonavir) 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 U.S. FDA and is working to submit applications to regulatory agencies around the world.
The company has entered into a voluntary license agreement with the Medicines Patent Pool to help expand access in 95 low- and middle-income countries that account for approximately 53% of the world’s population, pending authorization or approval
NEW YORKPfizer Inc. (NYSE: PFE) today announced an agreement with the U.S. government to supply 10 million treatment courses of its investigational COVID-19 oral antiviral candidate, PAXLOVID™ (PF-07321332; ritonavir), subject to regulatory authorization from the U.S. Food and Drug Administration (FDA). 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 (EUA) of PAXLOVID with the U.S. 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 U.S. government will acquire 10 million treatment courses to be delivered by Pfizer beginning later this year and concluding in 2022. Pfizer will receive $5.29 billion from the U.S. 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 U.S. 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.
“We were thrilled with the recent results of our Phase 2/3 interim analysis, which showed overwhelming efficacy of PAXLOVID in reducing the risk of hospitalization among high-risk patients treated within three days of symptom onset by almost 90% and with no deaths, and are pleased the U.S. government recognizes this potential,” said Albert Bourla, Chairman and Chief Executive Officer, Pfizer. “It is encouraging to see a growing understanding of the valuable role that oral investigational therapies may play in combatting COVID-19, and we look forward to continuing discussions with governments around the world to help ensure broad access for people everywhere.”
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.
Our Commitment to Equitable Access
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 $1 billion 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 (MPP) 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.
About the Phase 2/3 EPIC-HR Study Interim Analysis
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 (1:1) 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 7 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 10 subsequent deaths), with high statistical significance (p<0.0001). In the overall study population through Day 28, no deaths were reported in patients who received PAXLOVID as compared to 10 (1.6%) deaths in patients who received placebo.
The review of safety data included a larger cohort of 1,881 patients in EPIC-HR, whose data were available at the time of the analysis. Treatment-emergent adverse events were comparable between PAXLOVID (19%) and placebo (21%), most of which were mild in intensity. Among the patients evaluable for treatment-emergent adverse events, fewer serious adverse events (1.7% vs. 6.6%) and discontinuation of study drug due to adverse events (2.1% vs. 4.1%) were observed in patients dosed with PAXLOVID compared to placebo, respectively.
About the EPIC Development Program
The EPIC (Evaluation of Protease Inhibition for COVID-19) Phase 2/3 development program for PF-07321332; ritonavir consists of three clinical trials spanning a broad spectrum of patients, including adults who have been exposed to the virus through household contacts, as well as adults at both standard risk and high risk of progressing to severe illness.
In July 2021, Pfizer initiated the first of these trials, known as EPIC-HR, a randomized, double-blind study of non-hospitalized adult patients with COVID-19, who are at high risk of progressing to severe illness. At the recommendation of an independent Data Monitoring Committee and in consultation with the U.S. FDA, Pfizer has ceased further enrollment into the study due to the overwhelming efficacy demonstrated in these results.
In August 2021, Pfizer began the Phase 2/3 EPIC-SR (Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients), to evaluate efficacy and safety in patients with a confirmed diagnosis of SARS-CoV-2 infection who are at standard risk (i.e., low risk of hospitalization or death). EPIC-SR includes a cohort of vaccinated patients who have an acute breakthrough symptomatic COVID-19 infection and who have risk factors for severe illness. In September, Pfizer initiated the Phase 2/3 EPIC-PEP (Evaluation of Protease Inhibition for COVID-19 in Post-Exposure Prophylaxis) to evaluate efficacy and safety in adults exposed to SARS-CoV-2 by a household member. These trials are ongoing.
For more information on the EPIC Phase 2/3 clinical trials for PAXLOVID, visit clinicaltrials.gov.
About Pfizer: Breakthroughs That Change Patients’ Lives
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 170 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com. In addition, to learn more, please visit us on www.Pfizer.com and follow us on Twitter at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.
The information contained in this release is as of November 18, 2021. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.
This release contains forward-looking information about Pfizer’s efforts to combat COVID-19 and Pfizer’s investigational oral antiviral candidate PAXLOVID (including qualitative assessments of available data, potential benefits, expectations for clinical trials, a supply agreement with the U.S. government and the timing of delivery of doses thereunder, other advanced purchase agreements and an agreement with MPP, efforts toward equitable access, a submission to the FDA requesting EUA and submissions in other jurisdictions, the anticipated timing of data readouts, regulatory submissions, regulatory approvals or authorizations, planned investment and anticipated manufacturing, distribution and supply), involving substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as risks associated with preclinical and clinical data, including the possibility of unfavorable new preclinical, clinical or safety data and further analyses of existing preclinical, clinical or safety data; the ability to produce comparable clinical or other results including efficacy, safety and tolerability profile observed to date, in additional studies or in larger, more diverse populations following commercialization; the risk that preclinical and clinical trial data are subject to differing interpretations and assessments, including during the peer review/publication process, in the scientific community generally, and by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from these and any future preclinical and clinical studies; whether and when any drug applications or submissions to request emergency use or conditional marketing authorization for any potential indications for PAXLOVID may be filed in particular jurisdictions and if obtained, whether or when such emergency use authorization or licenses will expire or terminate; whether and when regulatory authorities in any jurisdictions may approve any such applications or submissions for PAXLOVID (including the submission for EUA pending with the FDA and rolling submissions in other jurisdictions), which will depend on myriad factors, including making a determination as to whether the product’s benefits outweigh its known risks and determination of the product’s efficacy and, if approved, whether it will be commercially successful; decisions by regulatory authorities impacting labeling or marketing, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of PAXLOVID, including development of products or therapies by other companies; risks related to the availability of raw materials for PAXLOVID; the risk that we may not be able to create or scale up manufacturing capacity on a timely basis or maintain access to logistics or supply channels commensurate with global demand, which would negatively impact our ability to supply the estimated numbers of courses of PAXLOVID within the projected time periods; whether and when additional purchase agreements will be reached; the risk that demand for any products may be reduced or no longer exist; uncertainties regarding the impact of COVID-19 on Pfizer’s business, operations and financial results; and competitive developments.
A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2020 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com.