Pfizer Takes Antiviral Drug PF-07304814 into Phase 1 Clinical Trial Targeting COVID-19

Pfizer Takes Antiviral Drug PF-07304814 into Phase 1 Clinical Trial Targeting COVID-19

Pfizer has initiated a Phase 1 clinical trial for a novel small molecule called PF-07304814, a compound targeting an enzyme that SARS-COV-2 uses to organize and multiply—the 3CL protease. With an idea of disrupting the novel coronaviruses’ ability to self-replicate and multiply, PF-07304814 represents the first antiviral drug targeting this protein. This novel investigational antiviral could possibly enhance the use of Remdesivir, for example.

The Investigational Product: PF-07304814

In a present Pfizer press release, the company announced its recent Protease Inhibitor Program including the Phase 1b clinical trial to evaluate the safety of the novel investigational therapeutic for COVID-19, PF-07304814.

Preclinical Evidence Basis for Phase 1 Clinical Trial

The company recently shared that this double-blind, placebo-controlled clinical trial evaluating the safety, tolerability and pharmacokinetics of the novel compound, a phosphate prodrug that when administered intravenously is metabolized to the active compound PF-00835321, shown to be a potent inhibitor of the SARS-CoV-2 3CL protease in preclinical studies.

Hence the basis for this study is backed by preclinical data conducted in collaboration with leading academic collaborators and demonstrates the anti-viral activity of this potential first-in-class SARS-CoV-2 therapeutic designed specifically to target COVID-19.

Backing all of this was two manuscripts authored to summarize the preliminary preclinical data currently uploaded on preprint servers at bioXriv, including this link and here

As it turns out, chemists working for Pfizer first identified this active compound nearly two decades ago during the SARS outbreak (2002-2003). Because that crisis never turned into an epidemic, let alone pandemic, the actual intellectual property put up on the shelf.

In a recent message to investors, Mikael Dolsten, Chief Scientific Officer for Pfizer, commented, “We believe this potential first-in-class protease inhibitor may give us the best opportunity to show meaningful antiviral activity to help treat COVID-19 patients.

Dolsten reported that PF-00835231 appears to be a potent inhibitor of coronaviruses or what he called “a pan-coronavirus protease inhibitor.”

The Study

According to Pfizer, the study was to start August 30, 2020. Titled A Phase 1b, 2-Part, Double-Blind, Placebo-controlled, Sponsor-open Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single Ascending (24 hour, Part 1) and Extended (120-hour, Part 2) Intravenous Infusions of PT-07304814 in Hospitalized Participants with Mild to Moderate COVID-19,” (NCT04535167) the study probes into the safety, tolerability and pharmacokinetics of PF07304814 in patients with SARS-CoV-2 virus infection and with mild-to-moderate symptoms.

The trial has a number of targeted endpoints for review. This treatment would require intravenous administration and hence hospitalization.

Orally-Available Agents Needed to Combat COVID-19

As reported in Chemical & Engineering NewsDennis C. Liotta, an antiviral expert and executive director of the Emory Institute for Drug Development—the organization that developed an orally-available SARS-CoV-2 antiviral that was ultimately licensed to Merck in May, commented, “The pressing need now continues to be the development of orally-available agents, which can be used broadly.”