- New Pharmacokinetic and Safety Results from Phase 1a Study of HBV Core Inhibitor EDP-514, Highlighting Good Safety and Tolerability, and Pharmacokinetics Suitable for Once Daily Dosing
- Phase 2a ARGON-1 Study for FXR Agonist EDP-305 Targeting NASH, Showing Significant Alanine Transaminase and Liver Fat Content Reduction
- Preclinical Findings for Follow-on FXR Agonist EDP-297 Targeting NASH, Demonstrating Potent Anti-Fibrotic, Anti-Inflammatory and Hepatoprotective Effects
WATERTOWN, Mass.--(BUSINESS WIRE)-- Enanta Pharmaceuticals, Inc. (NASDAQ:ENTA), a clinical-stage biotechnology company dedicated to creating small molecule drugs for viral infections and liver diseases, announced that data from Enanta’s wholly-owned development programs for non-alcoholic steatohepatitis (NASH) and hepatitis B virus (HBV) will be presented at the European Association for the Study of the Liver (EASL) Digital International Liver Congress™ 2020.
Data presented include results from the Phase 1a clinical trial of EDP-514, Enanta’s core inhibitor for HBV. Additionally, Enanta’s NASH program will be discussed in an oral presentation detailing the Phase 2a ARGON-1 study of EDP-305, Enanta’s lead Farnesoid X receptor (FXR) agonist, and two posters highlighting preclinical data on EDP-297, Enanta’s follow-on FXR agonist.
“We are pleased to share scientific data across multiple candidates in our pipeline, supporting our chemistry-driven approach to developing innovative treatments for viral infections and liver diseases,” stated Jay R. Luly, Ph.D., President and Chief Executive Officer of Enanta Pharmaceuticals. “The positive results from our first-in-human Phase 1a study of EDP-514, demonstrating a strong safety, tolerability and pharmacokinetic profile, gave us the confidence to advance our HBV program into two ongoing Phase 1b clinical studies in HBV patients. Additionally, the data presented for our NASH candidates further demonstrate the potential of both FXR agonists. EDP-305 shows statistically significant improvements in liver biochemistry and hepatic steatosis, and our follow-on NASH candidate EDP-297 demonstrates a potent anti-fibrotic effect.”
August 28, 2020, 12:15 PM - 12:30 PM CEST
ASO78: “EDP-305, a Non-Bile Acid Farnesoid X Receptor (FXR) Agonist, Showed Statistically Significant Improvements in Liver Biochemistry and Hepatic Steatosis in the Phase 2a ARGON-1 Study,” Vlad Ratziu, M.D., Ph.D., France
This oral presentation highlights the final results at week 12 of the randomized, double-blind, placebo-controlled Phase 2a ARGON-1 trial. The study’s primary endpoint was achieved with a statistically significant alanine transaminase (ALT) reduction of 28 U/L in the EDP-305 2.5mg arm versus 15 U/L in the placebo arm at week 12 (p=0.049). There was a statistically significant reduction in liver fat content with EDP-305 at the 2.5mg dose as measured by MRI-PDFF (p<0.001). EDP-305 also exhibited strong target engagement as shown by reductions in C4 and increases in FGF-19 and alkaline phosphatase (ALP). A robust gamma-glutamyl transferase (GGT) reduction was also observed. Overall, EDP-305 was generally safe, with the majority of treatment-emergent adverse events (TEAEs) being mild to moderate. In this study, mild to moderate pruritis was more frequent with the 2.5mg dose and there was a higher frequency of treatment discontinuation compared to the 1mg dose or placebo. Treatment with EDP-305 was associated with a modest effect on lipids as demonstrated by a minimal absolute change of 6 mg/dL, 5 mg/dL, and -4 mg/dL, with the 2.5mg dose, 1mg dose and placebo, respectively. These data warrant further development of EDP-305 in a NASH proven liver-biopsy patient population.
August 28, 2020, 09:30 AM - 19:30 PM CEST
FRI109: “EDP-297, a Novel and Potent FXR Agonist, Exhibits Robust Anti-Fibrotic Effects with Significant Liver Function Improvement in a Rat Model of Non-Alcoholic Steatohepatitis,” Mozhdeh Sojoodi, Ph.D., United States
Data in this poster demonstrate that treatment with EDP-297 significantly reduced fibrosis progression and improved liver function measured by key biomarkers in a rat model that closely resembles the human disease progression of NASH. Rats were randomized to receive either vehicle control (0.5% methylcellulose), 0.1 mg/kg EDP-297, or 0.3 mg/kg EDP-297 by once-daily oral gavage at the first signs of fibrosis (5 weeks, n=8 per group). EDP-297 demonstrated a highly statistically significant improvement in liver function as measured by a 78.9% reduction (p<0.001) in ALT, a 73.5% reduction (p<0.001) in aspartate aminotransferase (AST) and a 75.7% reduction (p<0.001) in total bilirubin. These results suggest that EDP-297 may have a potent anti-fibrotic effect in NASH patients, including those with late-stage F3/4 fibrosis.
August 29, 2020, 09:30 AM - 19:30 PM CEST
SAT042: “A Novel FXR Agonist EDP-297 Exerts Anti-Inflammatory and Hepatoprotective Effects in Human Liver 3D Microtissues and Rodent NASH and Liver Injury Models,” Mary Chau, Ph.D., United States
Data in this poster highlight the pharmacologic activity of EDP-297 as evaluated in multiple in vitro assays and further characterized in a human liver 3D microtissue system and in rodent models of NASH and liver injury. In 3D NASH microtissues, EDP-297 modulated multiple pathways associated with the pathogenesis of NASH. Specifically, decreased expression of genes encoding multiple lipogenic and inflammatory proteins was observed. EDP-297 treated rats with bile duct ligation showed significantly reduced expression of inflammatory and fibrotic genes and normalized circulating markers of liver injury, including ALT (76% reduction, p<0.001), AST (83% reduction, p<0.001) and GGT (76% reduction, p<0.001). Histological analysis confirmed the hepatoprotective effects of EDP-297 with reduced immune cell infiltration and necrosis. EDP-297 was shown to be hepatoprotective in a diet-induced obese NASH model in mice.
August 29, 2020, 09:30 AM - 19:30 PM CEST
SAT440: “EDP-514, a Novel Pangenotypic Class II Hepatitis B Virus Core Inhibitor: Final Results of a Phase 1 Study in Healthy Adult Subjects,” Kajal Larson, Ph.D., United States
Data in this poster present the safety and pharmacokinetic results of single ascending doses and multiple ascending doses of EDP-514 in a first-in-human, Phase 1 study. EDP-514 was rapidly absorbed and its exposure increased with escalating single and multiple dosing of 600 mg and 400 mg, respectively. EDP-514 was generally safe and well-tolerated over a broad range of single and multiple doses for up to 14 days, with all TEAEs being of mild severity. There were no severe or serious TEAEs and no discontinuations due to adverse events. Further, there were no significant individual lab data findings or pattern of lab abnormalities. EDP-514 exhibited pharmacokinetics suitable for once daily oral dosing. Following multiple dosing with EDP-514 when administered with and without a standard meal, the geometric mean plasma concentration at 24 hours (C24) was several fold higher than the in vitro serum protein adjusted EC50 (paEC50) of 71 ng/mL under fasted conditions (5.8- to 9.3-fold) and fed conditions (standard meal, 22.1-fold), suggesting that EDP-514 can be administered without regard to meals.
EDP-514 is currently being studied in two ongoing Phase 1b clinical studies, in viremic HBV patients, and in HBV patients treated with a nucleos(t)ide reverse transcriptase inhibitor (NUC-suppressed patients). Enanta anticipates reporting preliminary safety and virologic data from the viremic study in the first half of 2021, and preliminary data in NUC-suppressed patients in the second quarter of 2021.
The full scientific program for The Digital International Liver Congress 2020, as well as the abstracts, can be found at https://ilc-congress.eu/programme-digital-ilc-2020/.