Ipsen presented data at the American Association for the Study of Liver Diseases (AASLD) on the long-term efficacy and safety of Bylvay (odevixibat) in patients with Progressive Familial Intrahepatic Cholestasis (PFIC) and Alagille syndrome (ALGS). The data comes from two Phase III open-label extension studies, PEDFIC 2 and ASSERT-EXT, demonstrating sustained improvements in severe itch and serum bile acid levels.
Sustained Efficacy in PFIC Patients (PEDFIC 2 Study)
The PEDFIC 2 study (n=116) evaluated the efficacy and safety of Bylvay through 72 weeks (n=83) in patients with PFIC. The results indicated that 42% of patients under 18 years old with PFIC 1 and 2, who transitioned to Bylvay at 24 weeks (n=5/12), experienced a clinically meaningful 1-point reduction in pruritus score at week 72. Furthermore, 61% of patients with any type of PFIC and of any age, excluding episodic PFIC (n=19/31), also showed a similar reduction. Patients who achieved rapid initial pruritus score reductions by week 4 maintained these improvements throughout the treatment period. At 72 weeks, the mean change in serum bile acid (sBA) levels from baseline in patients who transitioned to Bylvay at week 24 (n=15) was -104.00 μmol/L, while in Bylvay-treated patients (n=43), it was -57.97 μmol/L.
Dr. Richard J. Thompson, Professor of Molecular Hepatology, 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."
Long-Term Benefits in ALGS Patients (ASSERT-EXT Study)
The ASSERT-EXT study (n=50) assessed the long-term efficacy and safety of Bylvay in ALGS patients (ages 1-15.9 years) through 72 weeks (n=44). The study revealed sustained improvements in pruritus and sBA levels. Specifically, 93% (n=28/30) of patients who received Bylvay throughout the 24-week ASSERT trial and 77% (n=10/13) of those who transitioned from placebo to Bylvay 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 patients continuously treated with Bylvay and a mean reduction of 139 μmol/L in patients who transitioned from placebo to Bylvay.
Improvements in height (8.2 cm) and weight (2.8 kg) were observed with continuous Bylvay use, and similar changes were reported for patients transitioning from placebo to Bylvay (height: 10.7 cm, weight: 3.3 kg).
Dr. Nadia Ovchinsky, Chief, Division of Gastroenterology and Hepatology, Hassenfeld Children’s Hospital at NYU Langone, commented, "The sustained improvements we’ve seen in Bylvay-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."
Safety and Tolerability
In both studies, the safety profile of Bylvay remained consistent with previous clinical trials. Most adverse events were mild or moderate, with gastrointestinal issues, including diarrhea, being the most common. In the PEDFIC 2 study, gastrointestinal events were reported in 17.2% of patients (n=20/116), with diarrhea occurring in 12% (n=14/116). In the ASSERT-EXT study, treatment-emergent adverse events (TEAE) occurred in 18% (n=6/33) of patients who continuously received Bylvay and 41% (n=7/17) of patients who transitioned from placebo to Bylvay. Diarrhea was the most common TEAE.
