Albireo’s Odevixibat Meets Endpoints in Late-Stage PFIC Study

Rare Daily Staff

Albireo Pharma said its experimental therapy odevixibat met its two primary endpoints in a late-stage study of patients with progressive familial intrahepatic cholestasis, a rare liver disease.

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 a procedure known as partial external biliary diversion (PEBD) and liver transplantation.

Odevixibat is being developed to treat PFIC, biliary atresia, and Alagille syndrome. A highly potent, non-systemic ileal bile acid transport inhibitor (IBATi), odevixibat has minimal systemic exposure and acts locally in the small intestine.

In the primary analysis, the study met the U.S. primary endpoint with the proportion of positive pruritus assessments being 53.5 percent in the odevixibat arms compared to 28.7 percent in the placebo arm. As a secondary endpoint, 42.9 percent 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 percent in the placebo arm.

The study also met the E.U. regulatory primary endpoint with 33.3 percent of subjects in the odevixibat arms experiencing either a 70 percent reduction in serum bile acids or reaching a level of 70 μmol/L compared to no patients in the placebo arm. 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 µmol/L 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 percent of odevixibat treated patients vs. 5.0 percent of placebo patients. Full results from the phase 3 clinical trial will be presented at a future scientific meeting.

“The successful clinical application of IBAT inhibition is all about the ability to lower bile acids and reduce diarrhea rates. Odevixibat reduced bile acids in both PFIC1 and PFIC2 patients and demonstrated a clinically meaningful outcome in pruritus. This is exciting news for children suffering from PFIC who, if odevixibat is approved, may soon have an easy to take, once-daily drug for their life-threatening liver disease,” said Ron Cooper, president and CEO of Albireo. “These strong results from PEDFIC 1 increase our confidence in the ongoing BOLD pivotal trial in biliary atresia and the Alagille syndrome study planned for later this year.”

Odevixibat has the potential to become the first approved pharmacologic treatment for patients with PFIC.  The company intends to complete regulatory filings in the European Union and in the United States no later than early 2021, in anticipation of potential regulatory approval, issuance of a rare pediatric disease priority review voucher and launch in the second half of 2021, if approved.

Albireo also plans to initiate a pivotal phase 3 trial of odevixibat in Alagille syndrome by the end of 2020, and to continue enrolling patients in the BOLD pivotal Phase 3 trial of odevixibat in biliary atresia. The company continues to progress its pipeline and expects to complete IND-enabling studies for a new preclinical candidate this year.

Photo: Ron Cooper, president and CEO of Albireo