Data presented at the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) 2024 provides insights into the safety of odevixibat (Bylvay) for treating cholestatic pruritus in pediatric patients with progressive familial intrahepatic cholestasis (PFIC). The focus was on diarrhea events associated with the once-daily, non-systemic ileal bile acid transport inhibitor.
Richard Thompson, MBChB, professor of Molecular Hepatology at King’s College London, who led the study, noted that the analysis aimed to assess treatment-emergent adverse events, particularly diarrhea, within the gastrointestinal disorders. The study also examined the severity, duration, and time to onset of these events, as well as their impact on dose adjustments or treatment discontinuation.
PEDFIC Trial Data
The analysis included pooled data from the PEDFIC 1 and PEDFIC 2 trials. PEDFIC 1 was a 24-week, randomized, placebo-controlled study involving children with PFIC1 or PFIC2 who had pruritus and elevated serum bile acids. Patients were randomized to receive either placebo, odevixibat 40 μg/kg, or odevixibat 120 μg/kg once daily. The trial, which enrolled 62 patients, met its primary endpoints, demonstrating that odevixibat was associated with reduced serum bile acid responses (P = .003) and improved pruritus assessments (P = .004) compared to placebo.
PEDFIC 2 is a 72-week open-label extension study that included patients from PEDFIC 1 and new patients of any age with any type of PFIC. The analysis presented at NASPGHAN 2024 included data from patients' first dose of odevixibat up to a cutoff date of July 31, 2022.
Safety and Tolerability Findings
The analysis included 119 patients with a median age of 3.6 years, of whom 45% were female. The median exposure to odevixibat was 82 weeks (range, 4 to 201 weeks). Results showed that 51% of patients experienced a treatment-emergent adverse event within the gastrointestinal disorders, with diarrhea being the most common, occurring in 24% of patients. All diarrhea events were reported as mild or moderate in severity and nonserious, with 90% resolving by the data cutoff.
The median duration of diarrhea events was 5 days, and drug-related diarrhea occurred in 11% of patients, with a median time to onset of 44 days. Dose reduction due to diarrhea was required for 3 patients, with symptoms resolving in 2 of these cases. Additionally, 5 patients experienced treatment interruptions due to diarrhea, with a median interruption duration of 4 days, and treatment was discontinued in 2 patients on odevixibat 120 µg/kg due to diarrhea.
Regulatory Context
Odevixibat was initially approved by the FDA in 2021 for treating cholestatic pruritus due to PFIC. In June 2023, it received an additional approval for treating cholestatic pruritus in patients 12 months and older with Alagille syndrome. These approvals were based on data from the PEDFIC 1 and PEDFIC 2 trials.
