Clin Mol Hepatol.
2024 Jul;30(3):375-387. 10.3350/cmh.2023.0535.
Phase 1 trial of the safety, pharmacokinetics, and antiviral activity of EDP-514 in untreated viremic chronic hepatitis B patients
- Yuen MF1
- Chuang WL2
- Peng CY3
- Jeng WJ4,5
- Su WW6
- Chang TT7,8
- Chen CY9
- Hsu YC10
- De La Rosa G11,12
- Ahmad A13
- Luo E13
- Conery AL
13
- Affiliations
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- 1Department of Medicine, School of Clinical Medicine, Queen Mary Hospital, and State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong
- 2Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- 3Center for Digestive Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan
- 4Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan
- 5College of Medicine, Chang Gung University, Taoyuan, Taiwan
- 6Department of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua, Taiwan
- 7Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- 8Infectious Disease and Signaling Research Center, National Cheng Kung University, Tainan, Taiwan
- 9Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan
- 10Center for Liver Diseases and School of Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
- 11Formerly Enanta Pharmaceuticals, Inc., Watertown, MA, USA
- 12Currently at Curevo Vaccine, Bothell, Washington, USA
- 13Enanta Pharmaceuticals, Inc., Watertown, MA, USA
- KMID: 2557390
- DOI: http://doi.org/10.3350/cmh.2023.0535
Abstract
- Background/Aims
Oral EDP-514 is a potent core protein inhibitor of hepatitis B virus (HBV) replication, which produced a >4-log viral load reduction in HBV-infected chimeric mice with human liver cells. This study evaluated the safety, pharmacokinetics, and antiviral activity of three doses of EDP-514 in treatment-naive viremic patients with HBeAgpositive or -negative chronic HBV infection.
Methods
Patients with HBsAg detectable at screening and at least 6 months previously were eligible. HBeAg-positive and -negative patients had a serum/plasma HBV DNA level ≥20,000 and ≥2,000 IU/mL, respectively. Twenty-five patients were randomized to EDP-514 200 (n=6), 400 (n=6) or 800 mg (n=7) or placebo (n=6) once daily for 28 days.
Results
A dose-related increase in EDP-514 exposure (AUClast and Cmax) was observed across doses. At Day 28, mean reductions in HBV DNA were –2.9, –3.3, –3.5 and –0.2 log10 IU/mL with EDP-514 200 mg, 400 mg, 800 mg, and placebo groups, respectively. The corresponding mean change from baseline for HBV RNA levels was –2.9, –2.4, –2.0, and –0.02 log10 U/mL. No virologic failures were observed. No clinically meaningful changes from baseline were observed for HBsAg, HBeAg or HBcrAg. Nine patients reported treatment emergent adverse events of mild or moderate severity with no discontinuations, serious AEs or deaths.
Conclusions
In treatment-naïve viremic patients, oral EDP-514 was generally safe and well-tolerated, displayed PK profile supportive of once-daily dosing, and markedly reduced HBV DNA and HBV RNA.
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