Intercept announces data from liver biopsy substudy of POISE Phase 3 trial
Intercept Pharmaceuticals 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, in Paris, France, from April 11-15, 2018. 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, 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 or maintained histological fibrosis stage, while two patients experienced one stage progression. Of the four patients with cirrhosis at baseline, all showed reversal by at least one stage, and three 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 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. 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 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 greater than or equal to0.67 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.