Paris, France – Ipsen (Euronext: IPN; ADR: IPSEY) announced today that Japan’s Ministry of Health, Labour and Welfare (MHLW) has granted regulatory approval for Bylvay® (odevixibat) for the treatment of pruritus associated with progressive familial intrahepatic cholestasis (PFIC). PFIC is a group of rare genetic disorders in which bile acid accumulates in the liver, leading to progressive liver damage and potentially liver failure. The condition severely impacts quality of life through debilitating symptoms such as severe itching (pruritus), caused by the bile accumulation in the liver and bloodstream, which can cause skin mutilation, sleep disruption, irritability, and impaired cognitive and social development.
“Children with PFIC often endure relentless itching that affects their daily quality of life. This includes regular, nightly sleep disturbance, which can have a negative impact on the whole family,” said Sandra Silvestri, MD, PhD, Executive Vice President, Chief Medical Officer, Ipsen. “The approval of Bylvay as a once-daily oral therapy represents a welcomed new option in how we approach this disease and offers new hope for patients and families in Japan living with the devastating impact of PFIC.”
Bylvay is a potent, once-daily, oral, ileal bile acid transport inhibitor (IBATi) that reduces reabsorption of bile acid back to the liver. In PEDFIC, the largest global Phase III trial conducted in PFIC, children treated with Bylvay showed significant improvements in serum bile acid and pruritus severity. The treatment was generally well-tolerated, with no drug-related serious adverse events and a low incidence of gastrointestinal events.
“Early diagnosis and intervention are critical in PFIC to manage symptoms and preserve liver function,” said Dr. Hiroki Kondou, Associate Professor, Department of Pediatrics, Kindai University Nara Hospital. “This approval of Bylvay provides patients and caregivers with a new treatment option that has the potential to reduce itching, and thereby improve sleep quality, while potentially supporting the preservation of liver.”
The approval from the MHLW was based on data from a Phase III, open-label study conducted in Japan, which evaluated the efficacy and safety of odevixibat in pediatric patients with PFIC types 1 and 2. The study confirmed improvements in serum bile acid levels and pruritus consistent with the global Phase III PEDFIC results. The Phase III clinical development plan for Bylvay in Japan was managed by Jadeite Medicines Inc and as part of the strategic collaboration, the new drug application for this indication was transferred to Ipsen headquartered in Tokyo, Japan. Ipsen will also be responsible for commercialization of Bylvay in Japan.
About PFIC
Progressive familial intrahepatic cholestasis (PFIC) is a group of rare genetic disorders in which bile acids build up in the liver, causing damage to the liver which may result in liver failure.2,3 There are several PFIC subtypes of which three are the most distinct : PFIC1 and PFIC2 typically manifest in the early stages of life – infancy or early childhood, while PFIC3 can have possible onset between infancy and adolescence.3,4 PFIC impacts males and females equally, at a rate ranging from 1 per 50,000 to 1 per 100,0005 births. While some late presentations of PFIC can present in adulthood, it typically manifests and is most aggressive in infants and young children.6 PFIC impacts patient’s daily lives through debilitating symptoms including severe itching (pruritus) which can result in skin mutilation, loss of sleep, irritability, poor attention, and impaired school function.4
About Bylvay (odevixibat)
Bylvay is a potent, once-daily ileal bile acid transport inhibitor (IBATi) that acts locally in the small intestine with minimal absorption into the rest of the body (minimal systemic exposure). Bylvay was approved in June 2021 in the EU as the first drug treatment option for all types of progressive familial intrahepatic cholestasis (PFIC) in patients aged 6 months or older, and in the US as the first drug treatment option for patients 3 months of age and older living with cholestatic pruritus due to PFIC. Bylvay has received orphan exclusivity for the treatment of PFIC in the EU and in the US In June 2023 Bylvay was approved in the U.S. for the treatment of cholestatic pruritus in patients from 12 months of age with ALGS and received orphan exclusivity for ALGS. In 2024 under the brand name Kayfanda (odevixibat), an approval under exceptional circumstances was granted by the European Commission for the treatment of cholestatic pruritus in Alagille syndrome (ALGS) in patients aged 6 months or older. Odevixibat is also in late-stage development in an ongoing Phase III clinical trial (BOLD) for the treatment of biliary atresia.
About PEDFIC
PEDFIC is the largest, global, Phase III trial ever conducted in PFIC. PEDFIC 1 is a randomized (1:1:1), double-blind, placebo-controlled 24-week trial that evaluated the efficacy and tolerability of two doses of odevixibat (40 μg/kg or 120 μg/kg) in reducing pruritus and serum bile acid levels in children with PFIC. The results were published in The Lancet.6
Data from the Phase III PEDFIC 1 trial demonstrated the potential for Bylvay to be an effective new treatment option for PFIC.6
- The PEDFIC trial (n=62) met its first primary endpoint, in which pruritus symptoms were significantly improved with odevixibat, with 55% of patients on odevixibat achieving a reduction in pruritus compared to 30% on placebo.
- The trial met its second primary endpoint of serum bile acid (sBA) response, defined as the number of patients who showed a reduction (either 70% or more from baseline, or levels of 70 μmol/L or less) in sBA at Week 24. Significantly more patients achieved a sBA response with odevixibat, with 33% of patients showing a reduction in sBA levels on odevixibat compared to no patients on placebo at Week 24.
- Odevixibat was generally well-tolerated, with no drug-related serious adverse events and a low incidence of diarrhea/frequent bowel movements reported during the trial.
PEDFIC 2, an open-label extension of PEDFIC 1, is an ongoing 72-week trial that aims to evaluate the efficacy and tolerability of odevixibat 120 µg/kg once a day in patients with PFIC. Interim results were published in The Journal of Hepatology.7
The approval from the Japanese MHLW was based on an open-label Phase III study conducted by Jadeite Medicines in Japan. Jadeite Medicines received Orphan Drug Designation for odevixibat in Progressive Familial Intrahepatic Cholestasis (PFIC) from the Ministry of Health, Labour and Welfare of Japan in May 2023, followed by the initiation of the Phase III trial in PFIC for patients in Japan. The study evaluated the efficacy and safety of odevixibat in pediatric patients with PFIC types 1 and 2 and confirmed improvements in serum bile acid levels and pruritus consistent with the global PEDFIC results.
About Ipsen
We are a global biopharmaceutical company with a focus on bringing transformative medicines to patients in three therapeutic areas: Oncology, Rare Disease and Neuroscience.
Our pipeline is fueled by external innovation and supported by nearly 100 years of development experience and global hubs in the U.S., France and the U.K. Our teams in more than 40 countries and our partnerships around the world enable us to bring medicines to patients in more than 100 countries.
Ipsen is listed in Paris (Euronext: IPN) and in the U.S. through a Sponsored Level I American Depositary Receipt program (ADR: IPSEY). For more information, visit ipsen.com.
Ipsen Investors Contacts
Henry Wheeler – [email protected] +33 7766471149
Khalid Deojee – [email protected] +33 666019526
Ipsen Media Contacts
Sally Bain – [email protected] +1 8573200517
Anne Liontas – [email protected] +33 0767347296
References
1Summar,y, Ministry of Health Labour and Wellbeing, Japan: 001175135.pdf Last accessed: September, 2025
2. Baker A, et al. Systematic review of progressive familial intrahepatic cholestasis. Clin Res Hepatol Gastroenterol. 2019. 43(1):20–36.
3. Nayagam JS, et al. Clinical phenotype of adult‐onset liver disease in patients with variants in ABCB4, ABCB11, and ATP8B1. Hepatol Commun. 2022. 6(10):2654-2664.
4. Agarwal S, et al. Progressive Familial Intrahepatic Cholestasis (PFIC) in Indian Children: Clinical Spectrum and Outcome. J Clin Exp Hepatol. 2016. v.6(3).
5. Davit-Spraul A, et al. Progressive familial intrahepatic cholestasis. Orphanet J Rare Dis. 2009. 4(1):1-12.
6. Thompson RJ, et al. Odevixibat treatment in progressive familial intrahepatic cholestasis: a randomised, placebo-controlled, phase 3 trial. Lancet Gastroenterol Hepatol. 2022. 7:830–842.
7. Thompson RJ, et al. Interim results from an ongoing, open-label, single-arm trial of odevixibat in progressive familial intrahepatic cholestasis 2023. JHEP Rep. 5(8):100782.