Liver Biopsy Data from POISE Phase 3 Substudy Supports Obeticholic Acid’s Ability to Reverse or Stabilize Fibrosis and Cirrhosis in Primary Biliary Cholangitis (PBC) Patients

11 of 13 patients improved or maintained histological fibrosis stage after three years of treatment with obeticholic acid (OCA)

NEW YORK, NY, USA I April 13, 2018 I Intercept Pharmaceuticals, Inc. (Nasdaq:ICPT) (Intercept), a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat progressive non-viral liver diseases, today announced clinical data from a liver biopsy-based substudy from the POISE Phase 3 trial suggesting that long-term OCA treatment in patients with PBC was associated with reversal or stabilization of fibrosis and cirrhosis. The data are being presented at the International Liver Congress™ 2018, the 53rd Annual Meeting of the European Association for the Study of the Liver (EASL), in Paris, France, from April 11-15, 2018.

“In this small but important study, some patients treated with OCA had regression of fibrosis and even cirrhosis. This is a significant finding because it further supports the clinical relevance of the biochemical improvements that predict the medication’s impact on disease progression and clinical outcomes,” said lead author Christopher Bowlus, M.D., University of California, Davis. “We look forward to the results of the Phase 4 COBALT study to further evaluate OCA’s effects on fibrosis regression and clinical outcomes in patients with PBC.”

OCA is not currently indicated for the reversal of fibrosis or cirrhosis in patients with PBC.

Prior longitudinal biopsy studies have shown that patients who are not treated with, or have an inadequate response to, ursodeoxycholic acid (UDCA), the current standard of care, are at significantly higher risk of fibrosis progression, liver failure, transplant and death. Liver biopsy is not the standard of care in PBC and difficult to obtain in clinical trials. In this voluntary substudy of the POISE Phase 3 trial, paired biopsies adequate for analysis were obtained for 13 patients, all of whom had liver fibrosis or cirrhosis at baseline.

After three years of treatment with OCA, the majority of patients improved (n=6, 46%) or maintained (n=5, 38%) histological fibrosis stage, while two patients (15%) experienced one stage progression. Of the four patients with cirrhosis at baseline, all showed reversal by at least one stage, and three (75%) improved to fibrosis without cirrhosis.

Pruritus is the most common symptom in patients with PBC and was also the most common adverse event in the POISE Phase 3 substudy. Nine (69%) patients experienced pruritus in the substudy, an incidence consistent with the rate observed in the broader study population. A total of five serious adverse events in five patients were reported. All serious adverse events were considered unlikely to be related, or not related, to OCA.

Additional Data Presentations

A separate poster, “Durable Response in the Markers of Cholestasis through 36 Months of Open-Label Extension Study of Obeticholic Acid in Primary Biliary Cholangitis,” presented at the International Liver Congress provided additional results from the open-label extension of the POISE trial. Sustained improvements in ALP were observed through three years of OCA therapy, with similar improvements seen for GGT, ALT and AST. Mean total bilirubin remained below baseline throughout the three-year open-label period. The most common adverse event observed with OCA therapy was pruritus, resulting in the discontinuation of seven patients (4%) during the open-label extension treatment phase.

An additional poster, “Change in Bilirubin with Obeticholic Acid Treatment in Primary Biliary Cholangitis Patients with High Baseline Bilirubin: A Retrospective Analysis of POISE, 201, and 202,” assessed changes in total bilirubin observed in the POISE Phase 3 trial and two Phase 2 trials. The analysis, which included patients with total bilirubin ≥0.67 times the upper limit of normal at baseline, found that total bilirubin increased after 12 months of placebo treatment and decreased after 12 months of treatment with OCA. In the double-blind phase of POISE, 14% of placebo-treated and 78% of OCA-treated patients with abnormal total bilirubin at baseline attained normal levels after 12 months. Further, of 10 placebo-treated and 20 OCA-treated patients with normal total bilirubin at baseline, 60% of placebo-treated and 15% of OCA-treated patients worsened to abnormal total bilirubin after 12 months. Per EASL clinical guidelines, increasing bilirubin levels – even within the normal range – indicate progressive disease and are strongly associated with adverse clinical outcomes.

About the POISE Trial
The POISE trial studied the safety and efficacy of once-daily treatment with OCA in PBC patients with an inadequate therapeutic response to, or who are unable to tolerate UDCA, the current standard of care. Of 216 patients randomized to three treatment arms—placebo, OCA 5 mg titrated to 10 mg or OCA 10 mg—93% continued receiving UDCA. The OCA 5-10 mg titration group received OCA 5 mg for six months, after which dosing was increased to 10 mg based on tolerability and biochemical response. The trial's primary endpoint was a reduction in ALP to below a threshold of 1.67 times the upper limit of normal, with a minimum of 15% reduction in ALP level from baseline and a normal bilirubin level after 12 months of therapy. The majority (97%) of the patients who completed the double-blind phase of the POISE trial entered an open-label extension.

About Primary Biliary Cholangitis
Primary biliary cholangitis (PBC) is a rare, autoimmune cholestatic liver disease that puts patients at risk for life-threatening complications. PBC is primarily a disease of women, afflicting approximately one in 1,000 women over the age of 40. If left untreated, survival of PBC patients is significantly worse than the general population.

About Ocaliva® (obeticholic acid)
In December 2016, Ocaliva received conditional marketing authorization in Europe for the treatment of PBC in combination with UDCA in adults with an inadequate response to UDCA or as monotherapy in adults unable to tolerate UDCA, conditional to the company providing further data post-approval to confirm benefit.

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 about Intercept, please visit www.interceptpharma.com or connect with the company on Twitter and LinkedIn.

SOURCE: Intercept

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