Ipsen's odevixibat (Bylvay/Kayfanda) has shown sustained efficacy and safety in treating patients with Progressive Familial Intrahepatic Cholestasis (PFIC) and Alagille Syndrome (ALGS), according to new data presented at the American Association for the Study of Liver Diseases (AASLD). The data, derived from open-label extension studies PEDFIC 2 and ASSERT-EXT, indicate that long-term treatment with odevixibat leads to significant improvements in pruritus (severe itch) and serum bile acid levels, along with positive effects on growth and sleep. These findings offer hope for patients and caregivers dealing with these rare and debilitating cholestatic liver diseases.
Sustained Efficacy in PFIC Patients
The PEDFIC 2 study, an open-label extension of the PEDFIC 1 trial, evaluated the efficacy and safety of odevixibat over 72 weeks in 116 patients with PFIC. The results indicated that 42% of patients under 18 years with PFIC 1 and 2, who transitioned to odevixibat at 24 weeks, experienced a clinically meaningful 1-point reduction in pruritus score at week 72. Furthermore, 61% of patients with any type of PFIC (excluding episodic) and of any age showed similar improvements. The mean change in serum bile acid (sBA) levels from patients who transitioned to odevixibat at week 24 was -104.00 μmol/L, while odevixibat-treated patients showed a reduction of -57.97 μmol/L.
Dr. Richard J. Thompson, Professor of Molecular Hepatology at King’s College London and principal investigator of the PEDFIC 2 trial, noted, "These open-label extension data from PEDFIC 2 suggest that the initial reduction in pruritus and in serum bile acid levels achieved following initiation of odevixibat are being sustained into the longer term. We are also observing reductions in both pruritus and serum bile acid across a number of PFIC subtypes. This is important information for our understanding of the therapeutic management of our patients living with PFIC."
Improvements in ALGS Patients
The ASSERT-EXT study assessed the long-term efficacy and safety of odevixibat in 50 ALGS patients (ages 1-15.9 years) over 72 weeks. The study demonstrated that 93% of patients who continuously received odevixibat throughout the 24-week ASSERT trial and 77% of those who transitioned from placebo to odevixibat at week 24 experienced a clinically meaningful ≥1 point reduction in pruritus score at week 72. Reductions in sBA levels were also observed, with a mean reduction of 124 μmol/L in those who continuously received odevixibat and a mean reduction of 139 μmol/L in patients who transitioned from placebo to odevixibat.
Dr. Nadia Ovchinsky, Chief of the Division of Gastroenterology and Hepatology at Hassenfeld Children's Hospital at NYU Langone, commented, "The sustained improvements we've seen in odevixibat-treated individuals living with Alagille syndrome are encouraging. These results not only show the potential to manage symptoms like pruritus, which can be extremely difficult for children and their parents to manage, but we’re also seeing a consistent safety profile over the longer term with sustained tolerability."
Additional Benefits and Safety Profile
Beyond the improvements in pruritus and sBA levels, both studies reported increases in height, weight, and improvements in sleep parameters among odevixibat-treated patients. The adverse events reported were mostly mild or moderate, with gastrointestinal issues, particularly diarrhea, being the most common. In the PEDFIC 2 study, diarrhea led to one treatment interruption and one discontinuation. In the ASSERT-EXT study, treatment-emergent adverse events occurred in 18% of patients who continuously received odevixibat and 41% of patients who transitioned from placebo to odevixibat.
About Odevixibat
Odevixibat, marketed as Bylvay in the U.S. and Europe and as Kayfanda in Europe, is a once-daily, non-systemic ileal bile acid transport (IBAT) inhibitor. It is approved for the treatment of cholestatic pruritus in patients with PFIC and ALGS. The drug works by reducing the reabsorption of bile acids in the ileum, thereby decreasing the levels of bile acids in the liver and serum.
