| Phase 1 Trial of the Safety, Pharmacokinetics, and Antiviral Activity of EDP-514 in Untreated Viremic Chronic Hepatitis B Patients |
| Man-Fung Yuen1, Wan-Long Chuang2, Cheng-Yuan Peng3, Wen-Juei Jeng4,5, Wei-Wen Su6, Ting-Tsung Chang7,8, Chi-Yi Chen9, Yao-Chun Hsu10, Guy De La Rosa11, Alaa Ahmad12, Ed Luo12, Annie L. Conery12 |
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, Taiwan
6Department of Gastroenterology and Hepatology, Changhua Christian Hospital, 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, Massachusetts, USA; Currently at Curevo Vaccine, Bothell, Washington, USA
12Enanta Pharmaceuticals, Inc., Watertown, Massachusetts, USA |
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Received: December 16, 2023 Revised: March 22, 2024 Accepted: March 25, 2024 |
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| ABSTRACT |
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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 (PK), and antiviral activity of three doses of EDP-514 in treatment naïve viremic patients with HBeAg-positive 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 (TEAEs) 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. |
| KeyWords:
chronic hepatitis B; hepatitis B virus; core inhibitor; core protein inhibitor; core protein allosteric modulator, capsid assembly modulator; pharmacokinetics; pharmacodynamics; safety |
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