| Intercept Announces New Data Analyses From FLINT Trial of Obeticholic Acid in NASH | Intercept Announces New Data Analyses From FLINT Trial of Obeticholic Acid in NASH
--Histologic improvements shown in OCA-treated patients regardless of fibrosis stage and in those at increased risk of rapid disease progression
--OCA-treated patients who initiated statins rapidly reversed LDL increases to below baseline levels
NEW YORK, March 20, 2015 (GLOBE NEWSWIRE) -- Intercept Pharmaceuticals, Inc. (Nasdaq:ICPT) (Intercept), a clinical stage biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat neglected chronic liver diseases, announced today new subgroup analyses from the Phase 2b FLINT trial of obeticholic acid (OCA) in patients with nonalcoholic steatohepatitis (NASH). Intercept is presenting the data in two posters during today's poster session at the American Association for the Study of Liver Disease (AASLD) and Industry Colloquium: Novel Targets and Therapies in Liver Disease.
Obeticholic acid (OCA) is a first-in-class farnesoid X receptor (FXR) agonist being developed for primary biliary cirrhosis (PBC), NASH and other chronic liver indications. Intercept has initiated a rolling New Drug Application with the FDA for PBC, and expects to complete the NDA and MAA submission in 2Q 2015. The commercial launch of OCA in the U.S. and Europe is planned in 2016. OCA was also recently granted breakthrough therapy designation by FDA for the treatment of NASH with liver fibrosis.
OCA Histological Effects in High-Risk NASH Patients
Established fibrosis is currently the best predictor of liver-related mortality in patients with NASH (Younossi, Hepatology 2011), and patients with early disease but with risk factors such as diabetes, obesity or elevated ALT are at risk of rapid progression to cirrhosis (Adams, J Hepatology 2005; Ekstedt, Hepatology 2006). The efficacy of OCA was evaluated in a high-risk subset of NASH patients in the FLINT trial more likely to experience liver-related clinical outcomes, defined as patients with a NAFLD activity score (NAS) of 4 or more and (i) advanced fibrosis (stage 2 or 3), or (ii) those with both early fibrosis (stage 1) and concomitant diabetes, obesity or elevated ALT. In this post hoc analysis of the high-risk subgroup (n=160; OCA=84; placebo=76), OCA-treated patients experienced improvements in NASH resolution (18% OCA vs 5% placebo, p=0.014), NAS by >=2 points (60% OCA vs 30% placebo, p=0.0004), and liver fibrosis by at least one stage (39% OCA vs 21% placebo, p=0.007). Further analysis of the observed fibrosis improvement in NASH patient subgroups with the greatest risk of progression demonstrated that OCA treatment resulted in at least one stage fibrosis improvement in obese patients (39% OCA vs 18% placebo, p=0.003) and patients with diabetes (43% OCA vs 18% placebo, p=0.009). In addition, fewer OCA-treated patients experienced fibrosis progression (17% OCA vs 29% placebo, p=0.047). The histologic benefits observed in OCA-treated patients occurred across all baseline fibrosis stages, supporting the potential for long-term OCA treatment to prevent progression to cirrhosis.
OCA Effects on Cardiometabolic Parameters
Patients with NASH generally experience cardiometabolic abnormalities that correspond to a relatively high cardiovascular disease risk and mortality. In the FLINT trial, OCA treatment for 72 weeks resulted in improvements in liver fibrosis (the hepatic feature most correlated with both cardiovascular and liver-related mortality) and other markers of cardiovascular risk, such as body weight (median: -1.7 kg OCA vs +0.6 kg placebo, p=0.001) systolic blood pressure (mean: -4.0 mmHg OCA vs -0.8 mmHg placebo, p=0.0331) and triglyceride/HDL ratio, a marker of cardiovascular risk and mortality (mean: -0.6 OCA vs 0.1 placebo, not significant). OCA treatment was not associated with changes in the Framingham Risk Score, a long-term measure of cardiovascular risk.
This post hoc analysis also evaluated the effect of statin use during FLINT. OCA-treated patients who initiated statins during the FLINT trial (n=26) experienced a rapid reversal of their observed mean LDL increase to below baseline levels, with a mean decrease after 72 weeks of treatment of -18.9 mg/dL. In contrast, other OCA-treated patients with no reported initiation or change in statin therapy experienced an increase in LDL that peaked at week 12 and was sustained over the 72 week treatment period. Patients treated with statins at baseline who maintained statin treatment over the duration of the study (n=50) experienced a mean LDL increase of 8.7 mg/dL at 72 weeks. Patients not treated with statins during the study (n=65) experienced a mean LDL increase of 16.0 mg/dL. Treatment related LDL increases in all groups reversed with treatment discontinuation. This post hoc analysis suggests that the OCA associated LDL increase reaches a maximum peak and plateaus soon after initiation of therapy and that concomitant statin use in NASH patients receiving OCA may ameliorate any treatment-related LDL increases.
Further, another new finding in this analysis was that statin use appeared to have an additive effect to OCA-related improvements in liver biochemistry parameters, while not impacting liver histology.
"Given the relatively high risk of progression to cirrhosis and mortality in this population of NASH patients with liver fibrosis and other co-morbidities, the findings being presented at the AASLD Colloquium add important new insights into the potential for OCA as a novel therapy to address a major unmet medical need," said David Shapiro, M.D., Chief Medical Officer of Intercept. "In addition to the histologic improvements in fibrosis and steatohepatitis seen in patients most at risk of progressing to cirrhosis, we are encouraged by the observation that OCA improved several important cardiometabolic parameters. Furthermore, the data support the potential for statins to effectively manage LDL and further improve liver enzymes, providing additional support for their use in NASH patients as currently recommended in the AASLD and EASL practice guidelines."
Previously Reported Safety and Tolerability Information
As previously reported in the primary analysis of FLINT, OCA was generally well tolerated. Adverse events were generally mild to moderate in severity and the incidence in the OCA and placebo treatment groups was similar for all symptoms except pruritus. Pruritus in the OCA treatment group occurred more frequently (23% vs 6%, p0.0001), at a higher grade (predominantly moderate pruritus) and resulted in one patient discontinuation. The incidence of severe or life threatening events was not different between the two treatment groups and most of the events in both groups were deemed to be unrelated to treatment, including all severe or life threatening cardiovascular events. As previously disclosed, two deaths occurred in the OCA treatment group, but neither was considered related to OCA treatment.
Research Analyst and Investor Event on March 20, 2015
Intercept management will host an event for research analysts and investors after the market close on Friday, March 20, 2015 with a presentation starting at 6:00 p.m. ET to discuss the data presented in the two posters. A live webcast of the presentation will be available on the investor page of Intercept's website at 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 required. A replay will also be available on the Intercept website approximately two hours after the completion of the event and will be archived for two weeks.
About FLINT
The Farnesoid X Receptor Ligand Obeticholic Acid in Nonalcoholic Steatohepatitis Treatment (FLINT) trial was sponsored by the National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK). FLINT enrolled 283 adult NASH patients at eight U.S. centers comprising the NIDDK's NASH clinical research network (CRN). Patients were randomized to receive either a 25-mg dose of OCA or placebo for 72 weeks. Patients enrolled in the trial were qualified based on a diagnosis determined by liver biopsy at the start of the trial with a NAFLD Activity Score (NAS) of four or greater and with a score of at least one in each component of the NAS eight point scale (steatosis 0-3, lobular inflammation 0-3, ballooning 0-2). End of trial biopsies were conducted in patients after the 72-week treatment period, with all biopsies centrally scored in a blinded fashion. Further details can be found at clinicaltrial.gov. The results from the FLINT trial were published online in The Lancet in November 2014.
About Nonalcoholic Steatohepatitis
NASH is a serious chronic liver disease caused by excessive fat accumulation in the liver that induces chronic inflammation which leads to progressive fibrosis (scarring) that can lead to cirrhosis, eventual liver failure and death. There are currently no drugs approved for the treatment of NASH. Studies have shown that 21-26% of NASH patients will develop cirrhosis over 8.2 years of follow-up and that liver-related mortality due to this disease is ten-fold that of the general population. According to recent epidemiological studies, it is estimated that more than 10% of the U.S. adult population has NASH with more than 60% of patients (potentially more than 14 million in total) believed to have liver fibrosis or cirrhosis due to progression of the disease. The proportion of liver transplants attributable to NASH has increased rapidly in past years and by 2020 the disease is projected to become the leading indication for liver transplant ahead of chronic hepatitis C and alcoholic liver disease. NASH patients with fibrosis are at greater risk of progressing to cirrhosis, liver failure and cancer.
About Intercept and Obeticholic Acid
Intercept is a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat neglected chronic liver diseases. The company's lead product candidate, obeticholic acid (OCA), is a first-in-class agonist of the farnesoid X receptor (FXR). OCA is being developed for a variety of chronic liver diseases, including primary biliary cirrhosis (PBC), nonalcoholic steatohepatitis (NASH), primary sclerosing cholangitis (PSC) and biliary atresia. The FDA has granted OCA breakthrough therapy designation for the treatment of NASH with fibrosis and granted OCA fast track designation for the treatment of patients with PBC who have an inadequate response to or are intolerant of ursodiol. OCA has also received orphan drug designation in both the United States and Europe for the treatment of PBC and PSC. Intercept owns worldwide rights to OCA outside of Japan, China and Korea, where it has out-licensed the product candidate to Sumitomo Dainippon Pharma. For more information about Intercept, please visit the Company's website at: www.interceptpharma.com.
Safe Harbor Statements
|
