Intercept Pharmaceuticals, Inc. , a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat progressive non-viral liver diseases, announced that the Phase 2 AESOP trial evaluating obeticholic acid (OCA) for the treatment of patients with primary sclerosing cholangitis (PSC) met its primary endpoint.
Patients who initiated OCA 5 mg with the option to titrate to 10 mg achieved a statistically significant reduction in alkaline phosphatase (ALP) as compared to placebo .
AESOP is a 24-week, double-blind, placebo-controlled, dose-ranging trial evaluating the efficacy and safety of OCA compared to placebo in 77 patients with PSC, followed by a two-year long term safety extension (LTSE) open-label phase which is currently ongoing. Patients were randomized to one of three treatment groups: placebo, OCA 1.5 — 3 mg, and OCA 5 — 10 mg (with dose titration occurring at the 12-week midpoint). Approximately half the patients were receiving ursodeoxycholic acid (UDCA) treatment at baseline and continued on a stable dose during the trial. The primary endpoint of the study was the change in ALP relative to placebo at week 24 for the OCA 5 — 10 mg group. Results for the intent-to-treat population are shown below.
Pruritus is a common symptom of PSC and was the most common adverse event observed in the AESOP trial, occurring in 46%, 60% and 67% of patients in the placebo, OCA 1.5 — 3 mg and OCA 5 — 10 mg groups, respectively. Pruritus severity increased with OCA treatment in a dose-dependent manner. One (4%) patient in the OCA 1.5 — 3 mg group and three (12%) in the 5 — 10 mg group discontinued treatment due to pruritus compared to none with placebo.
Other treatment emergent adverse events were similar across all three arms and the proportion of patients completing the double-blind period was similar across treatment groups (84%, 76% and 81% for placebo, OCA 1.5-3 mg and OCA 5-10 mg, respectively). Of these patients, 59 of 61 (97%) chose to participate in the LTSE phase.
“Currently there are no therapies proven to be effective in treating patients with PSC, a chronic liver disease that results in significant morbidity and mortality,” said Kris V. Kowdley, MD, Director, Liver Care Network and Organ Care Research, Swedish Medical Center, Seattle, and one of the lead investigators of the trial. “The results of this Phase 2 study of OCA are encouraging because patients achieved improvement in ALP, a marker of chronic cholestasis. There is a pressing need for innovation in this disease and, given these results, additional studies are warranted to better define the role of OCA as a treatment for PSC.”
“These results provide proof of concept for OCA in a second cholestatic liver disease with a very high unmet need,” said David Shapiro, M.D., Chief Medical Officer of Intercept. “We look forward to sharing the complete results from AESOP with the hepatology community at an upcoming scientific congress. We believe these data warrant further investigation and look forward to speaking with PSC thought leaders and regulators to help inform our future development plans.”
Intercept will discuss the AESOP results during its second quarter 2017 financial results conference call and webcast on July 31st at 8:30 a.m. ET. The live event will be available on the investor page of Intercept’s website at http://ir.interceptpharma.com or by calling (855) 232-3919 (toll-free domestic) or (315) 625-6894 (international) five minutes prior to the start time (no passcode is required). A replay of the call will be available on Intercept’s website approximately two hours after the completion of the call and will be archived for two weeks.
AESOP is a Phase 2 randomized, double-blind, placebo-controlled, dose-finding evaluation of the efficacy and safety of 24 weeks of treatment with obeticholic acid (OCA) compared to placebo in 77 patients with PSC. The primary endpoint of the AESOP trial is the LS mean change in serum alkaline phosphatase (ALP) levels, as compared to placebo. Patients with well-controlled irritable bowel disease (IBD) at baseline were permitted to enroll in the AESOP trial and patients receiving ursodeoxycholic acid (UDCA) treatment at baseline (approximately 50% of patients) were permitted to continue on a stable dose.
About Primary Sclerosing Cholangitis
Primary sclerosing cholangitis (PSC) is a rare, life-threatening, chronic cholestatic liver disease characterized by progressive destruction of bile ducts that leads to the development of cirrhosis and end-stage liver disease or cancer in a majority of patients.1-4 There are no approved therapies for PSC5, and estimated survival time from PSC diagnosis to death or liver transplant is 14.5 years.6 Approximately 65% of PSC patients are male4, and 60%-80% of patients have concomitant inflammatory bowel disease (IBD), most often ulcerative colitis.4,5,7 Although it is a rare disease, PSC is the seventh leading indication for liver transplant in adults in the United States.8,9
Intercept is a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat progressive non-viral liver diseases, including primary biliary cholangitis (PBC), nonalcoholic steatohepatitis (NASH), primary sclerosing cholangitis (PSC) and biliary atresia. Founded in 2002 in New York, Intercept now has operations in the United States, Europe and Canada. For more information about Intercept, please visit www.interceptpharma.com