Covid-19 Antiviral Efforts


Advancing Our Protease Inhibitors

Defeating COVID-19 likely requires both vaccination and targeted treatment for those who contract the virus. At Pfizer, we are evaluating two antiviral protease inhibitors – one orally administered candidate and one intravenously administered candidate – both of which have demonstrated potent antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as other known coronaviruses, in both in vitro and in vivo studies. We believe that, if successful and authorized or approved, these investigational therapies could provide important treatment options for adult COVID-19 patients, including those exposed to the virus by household contacts, those with diagnosed infections treated in the outpatient setting, and those hospitalized with moderate to severe infection.

Building on Pfizer’s expertise in developing antivirals, including a protease inhibitor for the treatment of HIV, Pfizer scientists commenced a drug discovery program in early 2020, shortly after COVID-19 emerged, with the goal of identifying a potential treatment to lower the impact of COVID-19 on patients’ lives and better prepare the world for future coronavirus threats. We initially evaluated our robust portfolio of therapeutics and screened some of the compounds from our 2003 SARS1 protease inhibitor preclinical program, given the similarities between the structures of the SARS-CoV-1 and the SARS-CoV-2 proteases.

In preclinical in vitro studies, many of the SARS-CoV-1 protease inhibitors identified in 2003 were found to also inhibit the SARS-CoV-2 protease. Optimization of our most promising SARS-CoV-1 protease inhibitor for intravenous (IV)-administration led to PF-07304814, which has recently completed a Phase 1b study, and we anticipate the initiation of a Phase 2/3 trial in 2021. If successful and authorized or approved, it would be a novel treatment option for hospitalized patients with COVID-19.

In parallel, we specifically and proactively designed a new SARS-CoV-2 protease inhibitor, PF-07321332, to be administered orally so that it could potentially be prescribed at the first sign of infection or at the first awareness of an exposure – without requiring patients to be hospitalized. In March 2021, Pfizer progressed PF-07321332 to a Phase 1 study in healthy adults to evaluate the safety, tolerability, and pharmacokinetics of the investigational compound. In July 2021, we progressed to a pivotal Phase 2/3 trial, EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients), to evaluate the efficacy and safety of PF-07321332, co-administered with a low dose of ritonavir, in participants with a confirmed diagnosis of SARS-CoV-2 infection who are at high risk of progression to severe illness. In August, we began a phase 2/3 trial, EPIC-SR (Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients), in participants with a confirmed diagnosis of SARS-CoV-2 infection who are at standard risk (i.e., do not have risk factors for severe illness). These studies are part of the global EPIC clinical development program, consisting of multiple ongoing and planned clinical trials to evaluate this early-intervention, outpatient therapeutic candidate for potential use in a broad population of patients.

PF-07321332 is the first orally administered coronavirus-specific investigational protease inhibitor to be evaluated in clinical studies.

If authorized or approved, both potential therapies may complement vaccination, providing treatment options for those who contract the virus.

Developing potential COVID-19 treatments is only possible through the dedicated work of our clinical research partners and individuals who volunteer to take part in clinical trials. We are grateful to each of the clinical trial investigators and their study teams who are partnering with us in this effort and to all the participants who have volunteered, and will volunteer, to help attempt to achieve our shared goal of making a difference for society.

1SARS is a viral respiratory illness caused by a coronavirus, which is part of the same family of viruses that cause COVID-19.

Learn more about our approach and efforts to bring a possible treatment to patients:

What kind of antivirals are Pfizer investigating?

Pfizer is investigating two protease inhibitors, one which is called PF-07304814 (and is IV-administered) and one which is called PF-07321332 (and is orally administered). In preclinical studies, both compounds have been shown to inhibit proteases used for replication by the coronavirus that is causing COVID-19.

How do antivirals contribute to the treatment of COVID-19?

Antivirals can help slow or stop a virus from replicating and thereby reduce the symptoms associated with COVID-19 and the risk of significant health complications. Both of the Pfizer investigational COVID-19 antiviral therapies currently being studied are protease inhibitors, which means they potentially work by interfering with an enzyme the coronavirus needs for replication.

When do you expect to announce results from these studies?

We initiated the Phase 1b study of PF-07304814 (which is IV-administered) in September 2020 and the Phase 1 study of PF-07321332 (which is orally administered) in March 2021. We plan to share results from these studies once analysis of the data is complete. We began a pivotal Phase 2/3 trial of PF-07321332 in July 2021, and we anticipate the initiaton of a Phase 2/3 trial for PF-07304814 in 2021.

Where can I learn more about current research findings?

Pfizer is committed to transparency on its research findings related to COVID-19, as set forth in the company’s five-point plan for the biopharmaceutical industry to tackle disease caused by the novel coronavirus.

As such, we have shared the chemical structure and pre-clinical development of our investigational IV-administered SARS-CoV-2-3CL protease inhibitor, PF-07304814, and its in vitro activity against coronaviruses, including SARS-CoV-2, the virus that causes COVID-19. We have published more about the structure and preclinical data in the Journal of Medicinal Chemistry, as well as a comparative analysis of the investigational IV-administered SARS-CoV-2-3CL protease inhibitor in the Journal of Virology. A preprint manuscript about the discovery of this novel inhibitor has been posted to BioRxiv. In addition, we shared the discovery of our oral protease inhibitor clinical candidate at the Spring American Chemical Society Meeting, and a preprint manuscript has been posted to medRxiv.

Further to our commitment to open data sharing, SARS-CoV-1 3CL protease inhibition data on 76 compounds and their molecular structures from the same chemical series as our investigational IV-administered SARS-CoV-2-3CL protease inhibitor is available in Data Notes (PDF), Structure Data Files (SDF), and Comma Separated Value File (CSV).

For additional information about Pfizer, please see our filings with the U.S. Securities and Exchange Commission, including the information provided in the sections captioned “Risk Factors” and “Forward-Looking Information and Factors that May Affect Future Results”.