Type: Orally available, potent, and selective small molecule dihydroorotate dehydrogenase (DHODH) inhibitor designed to block host cell de novo pyrimidine biosynthesis.
Status: Clear Creek said September 1 it received FDA clearance on an IND application to study its lead drug candidate brequinar as a COVID-19 treatment, and has dosed the first patient in the Phase Ia CRISIS trial (NCT04425252).
The randomized, open label, multi-center study will enroll up to 24 patients hospitalized with COVID-19, with the aim of assessing the preliminary efficacy, safety, and tolerability of brequinar. The study will assign participants 1:2 to standard of care or standard of care plus five once-daily oral doses of 100 mg brequinar. The primary endpoint is safety/tolerability measured by rates of post randomization adverse events and hematology/chemistry safety labs. The trial was recruiting at four sites in Hartford, CT; Jacksonville, FL; Philadelphia; and Tampa, FL.
Clear Creek cited in vitro and in vivo studies showing that brequinar has potent antiviral activity against a broad spectrum of viruses, including SARS-CoV-2. Additional in vitrodata has shown that brequinar led to increased effects of other antiviral therapies, including nucleoside analogs that are currently being evaluated for the treatment of COVID-19—potentially indicating that brequinar could be used in combination therapies, according to the company.
Brequinar is also under study in a Phase Ib/IIa trial (NCT03760666) designed to assess the safety, tolerability and efficacy of dose-adjusted brequinar in adult subjects with acute myeloid leukemia (AML). The antiviral drug ribavirin BID may be added to brequinar twice weekly in eligible subjects.
COVID-19: 200 Candidates and Counting
To navigate through the >200 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:
● FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.
● DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data.
● KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.
● TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.
GEN has also tagged the most common treatment types: