Ipsen's Kayfanda® (odevixibat) has been granted approval by the European Commission for the treatment of cholestatic pruritus in patients with Alagille Syndrome (ALGS) aged 6 months and older. The approval, announced on September 23, 2024, marks a significant advancement in the treatment of this rare liver disease, offering a new therapeutic option for young children suffering from the condition.
Kayfanda, also known as Bylvay® outside the EU, functions as a once-daily, non-systemic ileal bile acid transport (IBAT) inhibitor. The active substance, odevixibat, works by blocking the IBAT protein, which reduces the amount of bile acids that can form in the liver and subsequently alleviates the symptoms of cholestatic pruritus.
Clinical Evidence from ASSERT Trial
The European Commission's decision was primarily based on data derived from the Phase III ASSERT clinical trial. This trial, the only Phase III study completed specifically in patients with ALGS, demonstrated statistically significant and clinically meaningful improvements in scratching severity from baseline to month 6 in patients treated with Kayfanda compared to those receiving a placebo (p=0.002). These improvements were observed rapidly and maintained throughout the study period.
The ASSERT trial also revealed a statistically significant reduction in serum bile acid concentration at the end of treatment in the Kayfanda group versus the placebo group (p=0.001). Additionally, improvements were noted in multiple observer-reported sleep parameters. The overall incidence of treatment-emergent adverse events was similar between the Kayfanda and placebo groups, with a low rate of drug-related diarrhea reported in ALGS patients.
Impact on Alagille Syndrome Patients
Alagille Syndrome is a rare, inherited genetic disorder affecting multiple organs, including the liver, heart, skeleton, eyes, and kidneys. A key feature of ALGS is liver damage resulting from fewer than normal, narrowed, or malformed bile ducts, leading to a buildup of toxic bile acids, known as cholestasis. This cholestasis can cause fibrosis and progressive liver disease. Approximately 95% of ALGS patients present with chronic cholestasis within the first few months of life, and as many as 88% experience severe, intractable pruritus.
Professor Henkjan Verkade, Pediatric Gastroenterology and Hepatology at the University of Groningen, Beatrix Children’s Hospital, emphasized the significance of this approval: “ALGS is a distressing condition, which often presents in the first few months of life… To have a new treatment option that has been shown to reduce the itch and improve sleep is a very positive development for the ALGS community.”
Ipsen's Expanding Portfolio
With the approval of Kayfanda, Ipsen continues to solidify its position in the rare cholestatic liver disease space. Christelle Huguet, Executive Vice President and Head of Research and Development at Ipsen, stated, “Patients living with Alagille syndrome often endure a very poor quality of life as a result of the intolerable itch… Today’s decision is therefore very welcome.”
Ipsen has also received EU approval for Iqirvo® (elafibranor) for Primary Biliary Cholangitis, further demonstrating the company's commitment to addressing unmet needs in rare liver diseases. Kayfanda is also being studied in a Phase III trial, BOLD, for Biliary Atresia, with data anticipated in 2026.
