Albireo Pharma Reports Positive Data from Phase 3 Trial Evaluating Odevixibat for Rare Genetic Liver Disease

Albireo Pharma Reports Positive Data from Phase 3 Trial Evaluating Odevixibat for Rare Genetic Liver Disease

Albireo Pharmaceuticals announced positive topline results from PEDFIC 1, a global Phase 3 clinical trial evaluating odevixibat for progressive familial intrahepatic cholestasis (PFIC), a rare genetic disorder that causes progressive, life-threatening liver disease. The trial met its two primary endpoints and was safe and well tolerated. Albireo is on track to file regulatory submissions in the U.S. and E.U. by early 2021.

PEDFIC 1 was a randomized, double-blind, placebo-controlled, global multicenter trial in 62 patients, ages 6 months to 15.9 years, with PFIC type 1 or type 2. Patients were randomized to receive either a 40 µg/kg/day or 120 µg/kg/day oral dose of odevixibat or placebo once daily for 24 weeks. Patients randomized to odevixibat were treated with once-daily oral capsules or sprinkles. The trial had two primary endpoints. In the U.S., the endpoint was defined as change in pruritus from baseline over the last 5 months of the treatment period. The change in pruritus was indexed by caregiver-reported (Albireo ObsRO instrument) observed scratching compared to placebo. In the E.U. and the rest of the world, the primary endpoint was bile acid reduction measured from baseline to Week 24, measured as serum bile acid responses (sBAs) compared to placebo.

In the primary analysis, the study met the U.S. regulatory primary endpoint with the proportion of positive pruritus assessments of 53.5% in the odevixibat arms compared to 28.7% in the placebo arm. 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 μmol/L compared to no patients in the placebo arm. 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.

An open-label extension study, PEDFIC 2, is currently underway to assess long-term safety and durability of response. Cohort 1 of the trial allowed patients from the PEDFIC 1 clinical trial to continue treatment with odevixibat. Cohort 2 consists of patients who did not participate in the PEDFIC 1 trial and includes other forms of PFIC not included in PEDFIC 1.

About Odevixibat
Odevixibat a highly potent, non-systemic ileal bile acid transport inhibitor (IBATi). Odevixbat has minimal systemic exposure and acts locally in the small intestine. With normal function, approximately 95 percent of bile acids released from the liver into the bile ducts to aid in liver function are recirculated to the liver via the IBAT in a process called enterohepatic circulation. In people with cholestatic liver diseases, the bile flow is interrupted, resulting in elevated levels of toxic bile acids accumulating in the liver and serum. Accordingly, a product capable of inhibiting the IBAT could lead to a reduction in bile acids returning to the liver. Odevixbat does not require refrigeration and can be taken as a capsule for older children, or opened and sprinkled onto food, which are factors of key importance for adherence in a pediatric patient population.

About PFIC
Progressive familial intrahepatic cholestasis (PFIC) is a rare genetic disorder that causes progressive, life-threatening liver disease. People diagnosed with PFIC have impaired bile flow, or cholestasis, caused by genetic mutations. The resulting bile build-up in liver cells causes liver disease and symptoms. The most prominent and problematic ongoing manifestation of the disease is pruritus, or intense itching, which often results in a severely diminished quality of life. PFIC is also characterized by jaundice, and poor weight gain and growth. In many cases, PFIC leads to cirrhosis and liver failure within the first 10 years of life, and nearly all people with PFIC require treatment before age 30. There are no drugs currently approved for PFIC, only surgical options, including liver transplantation.