Enanta Announces Results of INTREPID Study of EDP-305 for the Treatment of Primary Biliary Cholangitis - Seite 2

Overall, EDP-305 was generally safe in subjects with PBC, with the majority of treatment-emergent adverse events (TEAEs) being mild to moderate. Five patients in the 2.5 mg arm experienced severe pruritus. The most common (≥10% or >1 subject/arm) TEAEs included pruritus, gastrointestinal-related symptoms (abdominal pain, diarrhea, gastro-esophageal reflux), headache and insomnia. These TEAEs are consistent with the safety profile observed across more than 400 subjects exposed to EDP-305 for up to 12 weeks. The incidence of treatment discontinuation due to pruritus in INTREPID was approximately 3% for the 1 mg EDP-305 treatment group and 18% for the 2.5 mg EDP-305 treatment group. Treatment with EDP-305 had no apparent effect on lipids, including cholesterol, low-density lipoproteins, high-density lipoproteins and triglycerides.

“While INTREPID did not meet the primary endpoint in subjects with PBC, as defined by at least a 20% reduction in ALP in the ITT set analysis, there were numerically higher response rates with 1 mg and 2.5 mg compared to placebo,” said Jay Luly, Ph.D., President and Chief Executive Officer of Enanta Pharmaceuticals. “In addition, as shown in the completer analysis, those subjects who finished treatment had a significant ALP response. We were also able to obtain actionable data from this study to help us advance EDP-305 and were encouraged that the lower dose of 1 mg could achieve much better tolerability, in terms of pruritus, without reducing the number of ALP responders or key biomarkers of target engagement also achieved at the 2.5 mg dose. This is an encouraging finding, particularly for the intermediate doses of 1.5 mg and 2.0 mg that we plan to take into our ARGON-2 study in non-alcoholic steatohepatitis (NASH) patients. One of those two doses in NASH could potentially achieve an efficacy and tolerability profile acceptable in NASH patients.”

Dr. Luly continued, “Rather than conducting further dose selection studies with EDP-305 in PBC, a disease for which there is already an approved second-line FXR agonist therapy, we intend to focus our future efforts with EDP-305 on NASH, a disease where FXR agonists like EDP-305 have the potential to be important components of drug combinations designed to give maximum benefit to patients. Our ARGON-2 study in NASH will explore new intermediate doses with the potential to optimize efficacy and tolerability, thereby maximizing the opportunity to develop EDP-305 in combination with other mechanisms of action against NASH.”