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.
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.”
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 News, Dennis 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.”