Therapy Areas: Respiratory
Enanta Pharmaceuticals Reports Positive Final Data from its Phase 1b Studies of EDP-514, a Novel Hepatitis B Virus Core Inhibitor
15 November 2021 - - US-based biotechnology company Enanta Pharmaceuticals, Inc. (NASDAQ: ENTA) has released final Phase 1b data for EDP-514, a novel pangenotypic class II hepatitis B virus core inhibitor, in conjunction with two posters presented at The Liver Meeting 2021, hosted by the American Association for the Study of Liver Diseases (AASLD), the company said.

822: "EDP-514, a Novel Pangenotypic Class II Hepatitis B Virus Core Inhibitor: Results of a 28-day Phase 1b Study in NUC-Suppressed CHB Patients"

Jordan J. Feld, MD, MPH, Toronto Centre for Liver Disease, University Health Network, Toronto, Canada

The poster highlights data from Part 2 of a Phase 1a/1b randomized, double-blind, placebo-controlled study assessing the safety, tolerability, pharmacokinetics and antiviral activity of three doses of EDP-514 in 24 NUC-suppressed chronic HBV patients who were either HBeAg-positive or HBeAg-negative. Patients were randomized to receive 200 mg, 400 mg, 800 mg of EDP-514 or placebo daily for 28 days.

Overall, EDP-514 was generally safe and well-tolerated at 200 mg, 400 mg, and 800 mg doses for 28 days.

EDP-514 was rapidly absorbed and its exposure increased with increasing multiple doses. EDP-514 exhibited pharmacokinetics suitable for once daily oral dosing, with Ctrough concentrations reaching up to ~20-fold above the protein-adjusted EC50. 

At Day 28, mean HBV RNA changes of -0.81, -1.12, 0.10, and -0.19 logs were observed in the 200 mg, 400 mg, 800 mg and placebo groups, respectively.

EDP-514 led to a maximum HBV RNA reduction of 2.3 log in HBeAg-negative and 2.8 log in HBeAg-positive subjects in EDP-514 arms compared to 1.2 log in the placebo arm.

In the EDP-514 800 mg arm, five of six subjects had either non-detectable or very low levels of HBV RNA at baseline; consequently, the effect of EDP-514 on HBV RNA could not be assessed in these subjects.

As expected in this NUC-suppressed patient population, there were no discernible changes in HBV DNA, HBeAg, HBcrAg, and HBsAg, and no instances of virologic failure were reported.

823: "EDP-514, a Novel Pangenotypic Class II Hepatitis B Virus Core Inhibitor Demonstrates Significant HBV DNA and HBV RNA Reductions in a Phase 1b Study in Viremic, Chronic Hepatitis B Infected Patients"

Man Fung Yuen, MBBS, MD, PhD, DSc, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong.

Data in this poster details results from a randomized, double-blind, placebo-controlled Phase 1b study evaluating the safety, pharmacokinetics and antiviral activity of three doses of EDP-514 in viremic chronic HBV patients, either HBeAg-positive or HBeAg-negative, and without cirrhosis.

Patients were randomized to receive 200 mg, 400 mg, or 800 mg of EDP-514 or placebo daily for 28 days with an 8-week follow-up period.

Results demonstrated that EDP-514 was safe and well-tolerated through 28 days of treatment, displayed pharmacokinetics supportive of once-daily dosing, and resulted in mean HBV DNA reductions of 2.9, 3.3, and 3.5 logs at 28 days for the 200 mg, 400 mg, and 800 mg cohorts, respectively, compared to 0.2 log in placebo.

HBV RNA was undetectable at Day 28 in 11 patients in the three EDP-514 cohorts as compared to none in placebo.

Mean HBV RNA reductions were 2.9, 2.4, and 2.0 logs for the 200 mg, 400 mg, and 800 mg cohorts, respectively, compared to 0.02 log in placebo.

EDP-514 is Enanta's lead HBV core inhibitor candidate. Core inhibitors, also known as capsid assembly modulators or core protein allosteric modulators, are a novel class of HBV 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 HBV covalently-closed circular DNA (cccDNA) in primary human hepatocytes when given early during HBV infection.

In vitro data also show that EDP-514 is pangenotypic, and that combinations of EDP-514 with a nucleoside reverse transcriptase inhibitor, the current anti-viral therapy for HBV, or with a class I core inhibitor, result in additive to synergistic antiviral effects. ln vivo models of EDP-514 demonstrate excellent efficacy with a greater than 4 log viral load reduction in HBV-infected PXB mice.

Hepatitis B is a viral infection that attacks the liver and can cause both acute and chronic disease. The virus is most commonly transmitted from mother to child during birth and delivery, as well as through contact with blood or other body fluids. It is estimated that over 290 m people worldwide have chronic HBV infection.

Current approaches to treatment include interferon therapy and/or NUCs. Treatment with interferon offers poor cure rates and is accompanied by serious side effects.2 NUCs can be very effective at suppressing the virus but rarely result in full eradication of the virus from the liver.

Enanta is using its robust, chemistry-driven approach and drug discovery capabilities to become a leader in the discovery and development of small molecule drugs for the treatment of viral infections and liver diseases.

Enanta's research and development efforts have produced clinical candidates currently in development for the following disease targets: respiratory syncytial virus, hepatitis B virus and SARS-CoV-2 (COVID-19). Enanta is also conducting research in human metapneumovirus.

Enanta's research and development activities are funded by royalties from hepatitis C virus products developed under its collaboration with AbbVie.

Glecaprevir, a protease inhibitor discovered by Enanta, is sold by AbbVie in numerous countries as part of its leading treatment for chronic HCV infection under the tradenames MAVYRET and MAVIRET (ex-US) (glecaprevir/pibrentasvir).
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