The rare liver disease can often lead to liver failure.
The US Food and Drug Administration (FDA) has approved odevixibat (Bylvay), the first ever treatment for pruritius in patients at least 3 months old with progressive familial intrahepatic cholestasis (PFIC), a rare progressive liver disease that commonly leads to liver failure.
The treatment, developed by Albireo Pharma, is a reversible inhibitor of the ileal bile acid transporter (IBAT) and decreases the reabsorption of bile acids from the small intestines.
The approval is based on a 24-week, randomized, double-blind, placebo-controlled trial involving 62 pediatric patients between 6 months and 17 years old with PFIC type 1 or type 2 and severe itching.
Each patient was randomized to receive either placebo or 40 mcg/kg or 120 mcg/kg.
The primary endpoints of the study were patient’s scratching as observed by their caregiver twice daily and assessed on a 5-point ordinal scale.
At the conclusion of the study, patients treated with odevixibat showed a greater decrease in itching or scratching compared to the placebo group.
Some of the adverse events found in study drug recipients included increases in liver enzymes and bilirubin.
The researchers conducted a second trial supporting the assessment of safety of the treatment. In the 72-week, open-label, single-arm study involving 79 participants with PFIC type 1, 2, and 3 between 4 months and 25 years old. The patients received either 120 mcg/kg of the study drug administered once daily.
The adverse events were similar between the 2 trials.
For healthy patients, cells in the liver drain bile acids into bile before the bile acid is removed from the liver. For patients with PFIC, liver cells cannot drain bile acids into the bile, causing the toxic substances to build up in the liver.
However, the exact cause of the itching in this patient population is not exactly known. It could be caused by increased levels of bile acids in the body and skin.
Odevixibat might not be effective for PFIC type 2 patients with ABCB11 variants, resulting in non-functional or absent bile salt export pump protein-3 (BSEP3).