Phase III PEDFIC 1 trial of A 4250 meets primary endpoints in progressive familial intrahepatic cholestasis.- Albireo

Albireo Pharma announced positive topline results from PEDFIC 1, a global Phase III clinical trial evaluating the efficacy and safety of A 4250 (odevixibat) and the largest study ever conducted in PFIC1 and PFIC2. PEDFIC 1 met its two primary endpoints, demonstrating that odevixibat reduced serum bile acid responses (sBAs) (p=0.003) and improved pruritus assessments (p=0.004) with a single digit diarrhea rate. Odevixibat is a highly potent, non-systemic ileal bile acid transport inhibitor (IBATi), for the treatment of progressive familial intrahepatic cholestasis (PFIC) patients. In the primary analysis, the study met the U.S. regulatory primary endpoint with the proportion of positive pruritus assessments being 53.5% in the odevixibat arms compared to 28.7% in the placebo arm (p=0.004). As a secondary endpoint, 42.9% of patients in the odevixibat arms had a clinically meaningful improvement in the pruritus score, defined as a drop from baseline of 1.0 point or more on the 0-4 point scale, at week 24 compared to 10.5% in the placebo arm (p=0.018). The study also met the EU regulatory primary endpoint with 33.3% of subjects in the odevixibat arms experiencing either a 70% reduction in sBAs or reaching a level of 70 micromol/L compared to no patients in the placebo arm (p=0.003). As a secondary endpoint, mean reduction of bile acids was 114.3 µmol/L in the odevixibat arms compared to an increase of 13.1 micromol/L in the placebo arm (p=0.002). Both doses of odevixibat were statistically significant for each of the endpoints. Odevixibat was well tolerated, with an overall adverse event incidence similar to placebo. There were no drug-related serious adverse events (SAEs) reported during the study. Diarrhea/frequent bowel movements were the most common treatment-related gastrointestinal adverse events which occurred in 9.5% of odevixibat treated patients vs. 5.0% of placebo patients. Full results from the Phase 3 clinical trial will be presented at a future scientific meeting.