Benzinga | Nov 12, 2021 07:17AM EST

Enanta Pharma Reports Final Data From Phase 1b Study Of EDP-514: Was Safe, Well Tolerated Up To 800mg

EDP-514 is Safe and Well-Tolerated up to 800 mg

Robust Antiviral Activity Demonstrated in Chronic Hepatitis B Virus Patients at All Doses

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, today announced final Phase 1b data for EDP-514, a novel pangenotypic class II hepatitis B virus (HBV) core inhibitor, in conjunction with two posters presented at The Liver Meeting(r) 2021, hosted by the American Association for the Study of Liver Diseases (AASLD).

"We are excited to present final data for EDP-514 from our Phase 1b studies in viremic and NUC-suppressed chronic HBV patients, giving us continued confidence in EDP-514 as a potential treatment for HBV," said Jay R. Luly, PhD, President and Chief Executive Officer of Enanta Pharmaceuticals. "At 800 mg, EDP-514 continues to demonstrate that it is safe and well-tolerated up to 28 days when dosed alone or in combination with NUC, as shown in the NUC-suppressed patients. Importantly, EDP-514 has robust antiviral activity across all dose groups, as best illustrated in the viremic patients where up to a 3.5 log decline in HBV DNA was observed. These data are supportive of a once-daily oral dosing regimen that could provide a foundation for a combination therapy approach to achieve functional cures for chronic HBV patients."

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 (n=6), 400 mg (n=6), 800 mg (n=6) of EDP-514 or placebo (n=6) 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 (n=6), 400 mg (n=6), or 800 mg (n=6) of EDP-514 or placebo (n=6) 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.