EDP-514 in healthy subjects and nucleos(t)ide reverse transcriptase inhibitor-suppressed patients with chronic hepatitis B

Jordan J. Feld, Eric Lawitz, Tuan Nguyen, Jacob Lalezari, Tarek Hassanein, Paul Martin, Steven Huy Han, Douglas Dieterich, Jeanne Marie Giard, Guy De La Rosa, Alaa Ahmad, Ed Luo, Annie L. Conery, Nathalie Adda

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Chronic hepatitis B (CHB) remains a major cause of morbidity and mortality. EDP-514 is a potent core inhibitor of hepatitis B virus (HBV) that reduces viral load reduction in HBV-infected chimeric mice. This first-in-human study evaluated the safety, tolerability, and pharmacokinetics (PK) of EDP-514 in healthy subjects and antiviral activity in patients with CHB. Methods: In Part 1, 82 subjects received placebo or EDP-514 in fed or fasted state as single ascending doses of 50–800 mg and multiple ascending doses of 200–800 mg for 14 days. In Part 2, 24 HBV DNA-suppressed, nucleos(t)ide (NUC)-treated (i.e., NUC-suppressed) CHB patients received EDP-514 200–800 mg or placebo for 28 days. Results: EDP-514 was well tolerated in healthy subjects and CHB patients with most adverse events of mild intensity. In Part 1, EDP-514 exposure increased in an approximately dose proportional manner up to 600 mg after single doses and up to 400 mg after 14-day dosing. In Part 2, EDP-514 exposure increased linearly with dose on Day 1 and Day 28, with some accumulation for Day 28 and median trough concentrations (Ctrough) approximately 20-fold above the protein-adjusted 50% effective concentration (EC50) for the dose range. Mean change in HBV RNA from baseline to Day 28 was −2.03, −1.67, −1.87, and −0.58 log U/mL in the 200 mg, 400 mg, 800 mg, and placebo CHB groups, respectively. Conclusions: EDP-514 was well tolerated, had a PK profile supporting once daily dosing, and reduced HBV RNA levels in NUC-suppressed CHB patients.

Original languageEnglish
JournalAntiviral Therapy
Volume27
Issue number6
DOIs
StatePublished - Dec 2022

Keywords

  • Chronic hepatitis B
  • capsid assembly modulator
  • core inhibitor
  • core protein allosteric modulator
  • hepatitis B virus
  • pharmacodynamics
  • pharmacokinetics
  • safety

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