Policy & Regulation
Enanta Pharmaceuticals Initiates Phase 1 Clinical Study of EDP-514, its Lead Core Inhibitor for the Treatment of Hepatitis B Virus
10 July 2019 - - US-based biotechnology company Enanta Pharmaceuticals, Inc. (NASDAQ: ENTA) has initiated part 1 of a Phase 1a/b clinical study of EDP-514, Enanta's lead core inhibitor for the treatment of hepatitis B virus, the company said.
The randomised, double-blind, placebo-controlled Phase 1a/b study is designed to evaluate first the safety, tolerability and pharmacokinetics of single ascending doses and multiple ascending doses of EDP-514 in healthy subjects (Part 1), and then the antiviral activity of EDP-514 in nucleos(t)ide-reverse-transcriptase -suppressed patients with chronic HBV infection (Part 2).
The study plans to enroll approximately 98 subjects and to evaluate up to 6 dose cohorts, with EDP-514 administered orally, once daily.
Following the completion of the SAD and MAD portion in healthy subjects, the study will evaluate safety, PK and antiviral data of EDP-514 in NUC-suppressed patients with chronic HBV infection.
EDP-514, a novel class II hepatitis B virus core inhibitor, is Enanta's lead core inhibitor candidate. Core inhibitors, also known as capsid assembly modulators or core protein allosteric modulators, are a novel class of replication inhibitors that have been shown to act at multiple steps in the HBV lifecycle.
Preclinical data demonstrate that EDP-514 is a potent inhibitor of HBV replication and prevents the de novo formation of new cccDNA in primary human hepatocytes when given early during HBV infection. 
In vitro data also show that EDP-514 is pan-genotypic, and that combinations of EDP-514 with nucleoside reverse-transcriptase inhibitors (NRTIs, current anti-viral therapies for HBV) or a class I core inhibitor result in additive to synergistic antiviral effects. ln vivo models of EDP-514 demonstrate excellent efficacy with >4-log viral load reduction in HBV-infected PXB mice.
Hepatitis B virus, or HBV, can cause a potentially life-threatening liver infection. The virus is transmitted through contact with the blood or other bodily fluids of an infected person.
It is estimated that approximately 250m people worldwide are chronically infected with HBV, and 15-25% of these patients develop chronic liver disease, including cirrhosis, liver cancer and/or liver decompensation. Current treatments for HBV offer modest cure rates and are accompanied by serious side effects.
New treatments that can provide functional cures to chronically infected patients are urgently needed.
Enanta's research and development efforts are currently focused on the following disease targets: respiratory syncytial virus, non-alcoholic steatohepatitis / primary biliary cholangitis, and hepatitis B virus.
Enanta's research and development activities are funded by royalties from HCV products developed under its collaboration with AbbVie.
Glecaprevir, a protease inhibitor discovered by Enanta, is now sold by AbbVie in numerous countries as part of its newest treatment for chronic hepatitis C virus infection. This leading HCV regimen is sold under the tradenames MAVYRET and MAVIRET (ex-US) (glecaprevir/pibrentasvir).