Treatment with Bylvay resulted in a “significantly greater” change from baseline to week 24 in mean scratching scores and serum bile acids vs. placebo among pediatric patients with Alagille syndrome, according to ASSERT study results.
Bylvay (odevixibat, Albireo Pharma/Ipsen), a selective inhibitor of the ileal bile acid transporter, received FDA approval in 2021 for treatment of pruritis in patients aged 3 months and older with progressive familial intrahepatic cholestasis, followed by FDA approval in 2023 for treatment of cholestatic pruritus among patients aged 12 months and older with Alagille syndrome, based on data from this study.
“The clinical presentation of Alagille syndrome is heterogeneous and varies in severity in individual patients,” Nadia Ovchinsky, MD, MBA, FAASLD, director of the division of pediatric gastroenterology and hepatology at NYU Grossman School of Medicine, and colleagues wrote in The Lancet Gastroenterology & Hepatology. “In addition to cholestasis and pruritus, other presenting symptoms and characteristic features of Alagille syndrome include jaundice, elevated bile acids and hepatic biochemical parameters, cardiovascular abnormalities, xanthomas and fat-soluble vitamin deficiencies.”
They continued: “Odevixibat has the potential to reduce systemic bile acid accumulation resulting from cholestasis and thus relieve pruritus, improve liver function and modify the progression of liver disease in Alagille syndrome without surgical intervention.”
In the phase 3, double-blind, placebo-controlled Alagille Syndrome Safety and Efficacy Randomized Trial (ASSERT), researchers compared change in caregiver-reported scratching score and serum bile acid concentration among 52 patients (median age, 5.5 years; 52% boys) with Alagille syndrome and a history of significant pruritis and elevated serum bile acids. Patients were randomly assigned to oral odevixibat 120 µg/kg per day (n = 35) or placebo (n = 17) for 24 weeks.
At baseline, both treatment and placebo groups had elevated mean scratching scores (2.8 vs. 3, respectively). From weeks 21 to 24, mean scratching scores were 1.1 (least-squares [LS] mean change = –1.7; 95% CI, –2 to –1.3) vs. 2.2 (LS mean change = –0.8; 95% CI, –1.3 to –0.3) — a “significantly greater” change from baseline for odevixibat compared with placebo (–0.9; 95% CI, –1.4 to –0.3).
Further, results demonstrated a greater reduction in mean serum bile acids from baseline to weeks 20 to 24 in the treatment group (–90 µmol/L; 95% CI, –133 to –48) vs. the placebo group (22 µmol/L; 95% CI, –35 to 80), a difference that favored odevixibat (LS mean change = –113 µmol/L; 95% CI, –179 to –47).
The most common treatment-emergent adverse events in both treatment and placebo groups were diarrhea (29% vs. 6%) and pyrexia (23% vs. 24%). Serious treatment-emergent adverse events were reported in 14% and 12%, respectively, although none required study discontinuation and no deaths were reported.
“Odevixibat could be an efficacious, nonsurgical option to reduce the systemic accumulation of bile acids that results from cholestasis, lessen the severity of pruritus and ultimately improve the standard of care in patients with Alagille syndrome,” Ovchinsky and colleagues wrote. “Given the 24-week timeframe and the small sample size of the current study, additional studies are needed to investigate both the short-term and longer-term safety and efficacy of odevixibat and establish this drug as a potential first-line treatment in patients with Alagille syndrome.”
Data is currently being collected in the ongoing open-label ASSERT extension study, researchers wrote, and will determine the effect of odevixibat on the need for biliary diversion or liver transplantation.
Collapse
Disclosures:
Ovchinsky reports receiving research support to her institution from Albireo Pharma and Mirum and consulting fees from Albireo Pharma. The study was funded by Albireo Pharma. Please see the study for all other authors’ relevant financial disclosures.
