Enanta’s study meets goal for its lead FXR agonist, EDP-305, for the treatment of NASH

Enanta’s study has met its primary endpoint, as ALT reduction at week 12, was met in the 2.5mg dosing group in testing its lead FXR agonist, EDP-305 for treatment of NASH, also meeting key secondary endpoint, reduction in liver fat content as measured by MRI-PDFF at week 12, in the 2.5mg dosing group.

WATERTOWN, Mass.–(BUSINESS WIRE)–Enanta Pharmaceuticals, Inc. (NASDAQ:ENTA), a research and development-focused biotechnology company dedicated to creating small molecule drugs for viral infections and liver diseases, today announced topline results from its ARGON-1 Phase 2a study of EDP-305 for the treatment of non-alcoholic steatohepatitis (NASH).

The ARGON-1 study was a 12-week, randomized, double-blind, placebo-controlled Phase 2a study evaluating the safety, tolerability, pharmacokinetics and efficacy of EDP-305 in a NASH population. The primary objectives of the study were to evaluate change in ALT levels at week 12 and to evaluate the safety and tolerability of EDP-305. Key secondary objectives included change in liver fat content by MRI-PDFF, change in lipids, and pharmacokinetics and pharmacodynamic parameters, including C4 and FGF19.

The study’s primary endpoint was achieved with a statistically significant 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).

As with our primary endpoint, 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). Forty-five percent (45%) of subjects were MRI-PDFF responders (i.e. ≥30% fat reduction). EDP-305 also exhibited strong target engagement as shown by reductions in C4 and increases in FGF-19 and ALP. A robust GGT reduction was also observed.

Overall, EDP-305 was generally safe, with the majority of treatment-emergent adverse events (TEAEs) being mild to moderate. The most common (≥5%) TEAEs included pruritus, gastro-intestinal (GI) related symptoms (nausea, vomiting, diarrhea), headache and dizziness. A consistent safety profile has been observed across more than 400 subjects exposed to EDP-305 across all studies to date. As for tolerability of EDP-305 in this 12-week Phase 2a study, pruritus was present in approximately 51% of the subjects in the 2.5mg arm compared to less than 10% in the 1mg arm, with the majority being mild or moderate in severity. The incidence of treatment discontinuation due to pruritus was 1.8% for 1mg and 20.8% for 2.5mg, with all the discontinuations in the 2.5mg arm being due to moderate pruritus.

Treatment with EDP-305 was associated with a very 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.

“Today’s statistically significant results demonstrate that EDP-305 is a potent FXR agonist that reduces ALT and has exhibited strong target engagement in NASH subjects,” stated Jay R. Luly, Ph.D., President and Chief Executive Officer. “Additionally, EDP-305 is differentiated from other FXR agonists in development today by its significant reduction in liver fat at 12 weeks. Our goal now is to initiate a 72-week Phase 2b study named ARGON-2 with histological endpoints in NASH patients, which we plan to initiate in the first half of calendar 2020.”

Professor Vlad Ratziu, MD, Pitié-Salpêtrière Hospital, Paris, France, the Principal Investigator for the study, said: “Based on data from ARGON-1, EDP-305 clearly displays enhanced efficacy over other second-generation FXR agonists currently in development. I look forward to EDP-305’s progress as an important member of the FXR agonist class of drugs.”

Professor Mary Rinella, MD, Department of Gastroenterology and Hepatology, Northwestern University, said: “EDP-305 demonstrated robust effects on liver fat and markers of liver injury. We look forward to Enanta’s Phase 2b study to understand how these observations may translate into meaningful histological benefits.”

Primary Biliary Cholangitis Program (PBC) and the INTREPID Study to contunie

Enanta also announced that it has determined, based on preliminary data, that its Phase 2 INTREPID study to assess the safety, tolerability, pharmacokinetics and efficacy of EDP-305 in subjects with Primary Biliary Cholangitis has achieved sufficient enrollment to provide actionable information for Enanta to make an informed decision about EDP-305 development for the treatment of PBC. Therefore, there will be no further enrollment in this study, and the study will continue as is in accordance with the latest data safety monitoring board (DSMB) recommendation.