Enanta Pharmaceuticals, Inc. (NASDAQ:ENTA), a clinical stage biotechnology company dedicated to creating small molecule drugs for viral infections and liver diseases, today announced positive data from the first two dose cohorts of its Phase 1b study of EDP-514 in viremic chronic HBV patients who were not being treated with a nucleoside reverse transcriptase inhibitor (NUC). The data demonstrated that EDP-514, Enanta's novel class II oral HBV core inhibitor, was safe and well-tolerated through 28 days of treatment, displayed pharmacokinetics (PK) supportive of once-daily dosing, and resulted in mean HBV DNA reductions of 2.9 and 3.3 logs at 28 days for the 200 mg and 400 mg cohorts, respectively.
"We are extremely pleased with these promising clinical results for EDP-514, which are comparable to the best antiviral effects reported for any core inhibitor to date and also extend the compound's excellent safety and tolerability profile," said Jay R. Luly, Ph.D., President and Chief Executive Officer of Enanta Pharmaceuticals. "In particular, we are encouraged by the rapid and robust declines in HBV DNA, which position EDP-514 to be a key component of a combination regimen for HBV. We believe EDP-514, in combination with a NUC and other mechanisms, could provide a foundation for an all-oral treatment approach to achieve functional cures in patients with chronic HBV infection. We look forward to progressing EDP-514 in combination with our oral HBV RNA destabilizer, EDP-721, a compound that has demonstrated significant reductions in HBsAg preclinically and which we expect to advance into the clinic mid-year. Ultimately, our all-oral, triple combination approach could provide potent suppression of multiple key steps in HBV replication, including HBV DNA, HBV RNA and HBsAg, to achieve our goal of developing a functional cure for HBV patients."
The randomized, double-blind, placebo-controlled Phase 1b study is evaluating the safety, pharmacokinetics, and antiviral activity of three doses of EDP-514 in viremic patients with chronic HBV infection, 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. The 800 mg cohort is ongoing and final study results will be presented at a future scientific conference.
Of the sixteen patients randomized in the first two dose cohorts (6 active and 2 placebo per cohort), majorities were male (56%), Asian (100%) and HBeAg-negative (94%), with a mean age of 45 years, mean baseline HBV DNA of 4.87 logs IU/mL, and mean baseline HBV RNA of 3.45 logs IU/mL. Overall, six patients reported treatment emergent adverse events (TEAEs) and all were mild except for 4 moderate events (2 in placebo and 2 in the 200 mg cohort) both of which were considered unlikely related to drug. No grade 3 TEAEs or serious adverse events, grade 3/4 clinical laboratory abnormalities, ALT/AST elevations or clinically relevant electrocardiogram (ECG) or vital sign changes were observed in the EDP-514 groups. EDP-514 exposure increased linearly with dose, with concentrations up to approximately 20-fold the protein-adjusted EC50 (9-fold for 200 mg, 20-fold for 400 mg).
At Day 28, mean reductions in HBV DNA were 2.9, 3.3, and 0.2 logs IU/mL in the 200 mg, 400 mg and placebo groups, respectively, with a maximum reduction of 4.2 logs vs. 0.5 log in placebo. HBV DNA was below the lower level of quantitation (LLOQ) in 4 patients treated with EDP-514 compared to none in the placebo group. Mean HBV RNA reductions of 2.9, 2.4 and 0.3 logs IU/mL were observed in the 200 mg, 400 mg and placebo groups, respectively, with a maximum reduction of 4.8 logs vs. 1.9 logs in placebo. HBV RNA was undete...
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