- OCA met the primary endpoint of alkaline phosphatase (ALP) reduction at 24 weeks
- Results presented in a late-breaking oral session
NEW YORK, NY, USA I October 23, 2017 I Intercept Pharmaceuticals, Inc. (Nasdaq:ICPT), a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat progressive non-viral liver diseases, today announced additional results from the Phase 2 AESOP trial evaluating the investigational therapy obeticholic acid (OCA) for the treatment of patients with primary sclerosing cholangitis (PSC). These data were presented by lead investigator Kris Kowdley, M.D., Director, Liver Care Network and Organ Care Research, Swedish Medical Center, Seattle, in a late-breaking oral session at The Liver Meeting® 2017, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), in Washington, D.C.
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. 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).
OCA achieved the primary endpoint of the AESOP trial: patients receiving 5 mg of OCA daily with the option to titrate to 10 mg achieved a statistically significant reduction in alkaline phosphatase (ALP) as compared to placebo at week 24 (p<0.05). The results from this dose-ranging study suggest that 5 mg may be the optimal titrated dose of OCA in this patient population.
| |
|
| (U/L) |
Placebo
(N = 25) |
OCA 1.5-3 mg
(N = 25) |
OCA 5-10 mg
(N = 26) |
| Mean Baseline ALP |
563 |
423 |
429 |
| Least Squares (LS) Mean Change from Baseline in ALP at Week 12 |
-53 |
-57 |
-135* |
| LS Mean Change from Baseline in ALP at Week 24 |
-27 |
-105 |
-110*† |
| LS Mean Percent Change from Baseline at Week 24 |
+1% |
-22%* |
-22%* |
* p<0.05
† Primary endpoint was ALP change for OCA 5-10 mg compared to placebo at week 24.
Patients in the OCA 1.5-3 mg group also achieved statistically significant reductions in ALP versus placebo as measured by LS mean percent change from baseline at week 24. By week 24, ALP increased 1% in the placebo group and decreased by 22% in both the OCA 1.5-3 mg and OCA 5-10 mg groups (p<0.05).
There are currently no approved medications for PSC. Some patients are treated with ursodeoxycholic acid (UDCA) even though the AASLD treatment guidelines for PSC recommend against its use. In AESOP, a significant proportion of patients used UDCA, with 48%, 48% and 46% of patients on placebo, OCA 1.5-3 mg and OCA 5-10 mg, respectively, receiving UDCA at baseline.
In a post-hoc analysis examining the effects of OCA in the presence and absence of UDCA, ALP reductions were observed with OCA regardless of treatment with UDCA. Patients receiving OCA monotherapy had greater reductions in ALP at week 12 and week 24 as compared to patients who received OCA in addition to UDCA. At week 12, patients in the OCA 5-10 mg group receiving OCA monotherapy achieved a 30% LS mean reduction in ALP as compared to a 16% reduction in patients receiving OCA in combination with UDCA. At week 24, LS mean reductions in ALP in the OCA 5-10 mg group were 25% for patients receiving OCA monotherapy and 14% for patients receiving OCA in combination with UDCA.
| |
– UDCA |
+ UDCA |
| Placebo |
OCA 1.5-3 mg |
OCA 5-10 mg |
Placebo |
OCA 1.5-3 mg |
OCA 5-10 mg |
| LS Mean Percent Change from Baseline in ALP at Week 12 |
-5 |
% |
-12 |
% |
-30 |
% |
-1 |
% |
-1 |
% |
-16 |
% |
| LS Mean Percent Change from Baseline in ALP at Week 24 |
-7 |
% |
-19 |
% |
-25 |
% |
19 |
% |
-15 |
% |
-14 |
% |
Pruritus is a common symptom of PSC and was the most common adverse event observed in AESOP, occurring in 46%, 60% and 67% of patients in the placebo, OCA 1.5-3 mg and OCA 5-10 mg groups, respectively.
A two-year open-label extension of AESOP remains ongoing. Of those patients who completed the double-blind phase of the AESOP trial, 97% chose to participate in the open-label extension phase.
“There is an urgent need for effective therapies in PSC, a rare cholestatic liver disease which can lead to cirrhosis, cholangiocarcinoma and premature mortality,” said Dr. Kowdley. “These proof-of-concept results from the AESOP trial are encouraging and represent an important contribution to the growing momentum in PSC research. Further analyses of the AESOP results will help us better understand the effects of OCA in key subpopulations of interest.”
About AESOP
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%) 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. There are no approved therapies for PSC, and estimated survival time from PSC diagnosis to death or liver transplant is 14.5 years. Approximately 65% of PSC patients are male, and 60%-80% of patients have concomitant inflammatory bowel disease (IBD), most often ulcerative colitis. Although it is a rare disease, PSC is the seventh leading indication for liver transplant in adults in the United States.
About Intercept
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, please visit www.interceptpharma.com or connect with the company on Twitter and LinkedIn.
SOURCE: Intercept Pharmaceuticals
Post Views: 166
- OCA met the primary endpoint of alkaline phosphatase (ALP) reduction at 24 weeks
- Results presented in a late-breaking oral session
NEW YORK, NY, USA I October 23, 2017 I Intercept Pharmaceuticals, Inc. (Nasdaq:ICPT), a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat progressive non-viral liver diseases, today announced additional results from the Phase 2 AESOP trial evaluating the investigational therapy obeticholic acid (OCA) for the treatment of patients with primary sclerosing cholangitis (PSC). These data were presented by lead investigator Kris Kowdley, M.D., Director, Liver Care Network and Organ Care Research, Swedish Medical Center, Seattle, in a late-breaking oral session at The Liver Meeting® 2017, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), in Washington, D.C.
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. 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).
OCA achieved the primary endpoint of the AESOP trial: patients receiving 5 mg of OCA daily with the option to titrate to 10 mg achieved a statistically significant reduction in alkaline phosphatase (ALP) as compared to placebo at week 24 (p<0.05). The results from this dose-ranging study suggest that 5 mg may be the optimal titrated dose of OCA in this patient population.
| |
|
| (U/L) |
Placebo
(N = 25) |
OCA 1.5-3 mg
(N = 25) |
OCA 5-10 mg
(N = 26) |
| Mean Baseline ALP |
563 |
423 |
429 |
| Least Squares (LS) Mean Change from Baseline in ALP at Week 12 |
-53 |
-57 |
-135* |
| LS Mean Change from Baseline in ALP at Week 24 |
-27 |
-105 |
-110*† |
| LS Mean Percent Change from Baseline at Week 24 |
+1% |
-22%* |
-22%* |
* p<0.05
† Primary endpoint was ALP change for OCA 5-10 mg compared to placebo at week 24.
Patients in the OCA 1.5-3 mg group also achieved statistically significant reductions in ALP versus placebo as measured by LS mean percent change from baseline at week 24. By week 24, ALP increased 1% in the placebo group and decreased by 22% in both the OCA 1.5-3 mg and OCA 5-10 mg groups (p<0.05).
There are currently no approved medications for PSC. Some patients are treated with ursodeoxycholic acid (UDCA) even though the AASLD treatment guidelines for PSC recommend against its use. In AESOP, a significant proportion of patients used UDCA, with 48%, 48% and 46% of patients on placebo, OCA 1.5-3 mg and OCA 5-10 mg, respectively, receiving UDCA at baseline.
In a post-hoc analysis examining the effects of OCA in the presence and absence of UDCA, ALP reductions were observed with OCA regardless of treatment with UDCA. Patients receiving OCA monotherapy had greater reductions in ALP at week 12 and week 24 as compared to patients who received OCA in addition to UDCA. At week 12, patients in the OCA 5-10 mg group receiving OCA monotherapy achieved a 30% LS mean reduction in ALP as compared to a 16% reduction in patients receiving OCA in combination with UDCA. At week 24, LS mean reductions in ALP in the OCA 5-10 mg group were 25% for patients receiving OCA monotherapy and 14% for patients receiving OCA in combination with UDCA.
| |
– UDCA |
+ UDCA |
| Placebo |
OCA 1.5-3 mg |
OCA 5-10 mg |
Placebo |
OCA 1.5-3 mg |
OCA 5-10 mg |
| LS Mean Percent Change from Baseline in ALP at Week 12 |
-5 |
% |
-12 |
% |
-30 |
% |
-1 |
% |
-1 |
% |
-16 |
% |
| LS Mean Percent Change from Baseline in ALP at Week 24 |
-7 |
% |
-19 |
% |
-25 |
% |
19 |
% |
-15 |
% |
-14 |
% |
Pruritus is a common symptom of PSC and was the most common adverse event observed in AESOP, occurring in 46%, 60% and 67% of patients in the placebo, OCA 1.5-3 mg and OCA 5-10 mg groups, respectively.
A two-year open-label extension of AESOP remains ongoing. Of those patients who completed the double-blind phase of the AESOP trial, 97% chose to participate in the open-label extension phase.
“There is an urgent need for effective therapies in PSC, a rare cholestatic liver disease which can lead to cirrhosis, cholangiocarcinoma and premature mortality,” said Dr. Kowdley. “These proof-of-concept results from the AESOP trial are encouraging and represent an important contribution to the growing momentum in PSC research. Further analyses of the AESOP results will help us better understand the effects of OCA in key subpopulations of interest.”
About AESOP
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%) 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. There are no approved therapies for PSC, and estimated survival time from PSC diagnosis to death or liver transplant is 14.5 years. Approximately 65% of PSC patients are male, and 60%-80% of patients have concomitant inflammatory bowel disease (IBD), most often ulcerative colitis. Although it is a rare disease, PSC is the seventh leading indication for liver transplant in adults in the United States.
About Intercept
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, please visit www.interceptpharma.com or connect with the company on Twitter and LinkedIn.
SOURCE: Intercept Pharmaceuticals
Post Views: 166
