Enanta: Positive Phase 1 Data on Oral 3CL Protease Inhibitor Treatment of COVID-19

  Enanta Pharmaceuticals, Inc.. (NASDAQ: ENTA), a clinical-stage biotechnology company dedicated to creating novel, small molecule drugs for viral infections and liver diseases, today announced positive topline data from a Phase 1 study assessing the safety, tolerability, and pharmacokinetics (PK) of orally administered single ascending doses (SAD) and multiple ascending doses (MAD) of EDP-235 in healthy adult subjects. EDP-235, a coronavirus 3CL protease inhibitor, which received Fast Track designation from the U.S. Food and Drug Administration (FDA), is specifically designed to be a once-daily, oral antiviral treatment for COVID-19. Data from the Phase 1 study demonstrated favorable safety, tolerability, and PK with strong exposure multiples over the EC₉₀, thereby supporting the advancement of EDP-235 into a Phase 2 study using once-daily dosing, without ritonavir.

“We are very pleased with the encouraging results from our Phase 1 study of EDP-235 showing that it was generally safe and well-tolerated up to a once-daily dose of 400mg, which provided plasma drug levels that were 6-fold and 12-fold over the plasma protein adjusted EC₉₀ for the Alpha variant and the Delta variant, respectively. Moreover, EDP-235 is projected to have four times higher drug levels in lung tissue compared to plasma, which would drive exposure multiples to 24-fold and 48-fold for the respective variants,” stated Jay R. Luly, Ph.D., President and Chief Executive Officer of Enanta Pharmaceuticals. “Preclinical data show good distribution into other key target tissues, which may allow EDP-235 to inhibit the virus at possible sites of ongoing replication potentially linked to long COVID. Our data support a convenient dosing regimen, with strong exposure multiples for both the 200mg and 400mg doses, without the need for ritonavir boosting. We are targeting a one pill, once-a-day antiviral treatment regimen that is active against all COVID-19 variants of concern and look forward to moving EDP-235 into a Phase 2 study in the fourth quarter of this year.”

This first-in-human, randomized, double-blind, placebo-controlled Phase 1 study enrolled healthy volunteers to evaluate the safety, tolerability, and PK of oral EDP-235 in SAD and MAD for seven days, and the effect of food. All SAD and MAD cohorts enrolled eight participants who were randomized to receive EDP-235 or placebo in a 3:1 ratio. To optimize dose selections, the study evaluated a broad range of single and multiples doses in fasted and fed states. The SAD phase included five cohorts (50mg to 800mg, fasted and/or fed) and the MAD phase included four cohorts (200mg to 800mg, fasted and/or fed).

A total of 72 subjects (n=40 in SAD; n=32 in MAD) received at least one dose of EDP-235 or placebo. Overall, EDP-235 was generally safe and well-tolerated in healthy subjects up to 400mg for up to seven days. The majority of adverse events (AEs) were mild, with headache and gastrointestinal related symptoms (e.g. nausea, abdominal discomfort) being the most frequently reported AEs during the MAD phase. There were three study discontinuations: one moderate headache in the 400mg fasted cohort, one severe headache in the 800mg fed cohort and one grade 3 ALT/grade 2 AST elevation in the 800mg fed cohort.

https://www.biospace.com/article/releases/enanta-pharmaceuticals-announces-positive-data-from-a-phase-1-clinical-study-of-edp-235-its-oral-3cl-protease-inhibitor-designed-for-the-treatment-of-covid-19/