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.