U.S. FDA approves Bylvay® for patients living with cholestatic pruritus due to Alagille syndrome

• Approval heralds the second rare cholestatic liver disease indication for Bylvay in the U.S. after progressive familial intrahepatic cholestasis related pruritus in 2021
• Immediate U.S. commercial launch and availability for eligible patients
• ASSERT clinical study demonstrated efficacy of Bylvay in improvement of pruritus. Also showed improvement in certain sleep disturbances and reduction in bile acids – which were secondary endpoints – with a low drug-related diarrhea rate in patients with Alagille syndrome
• Committee for Medicinal Products for Human Use opinion expected in Q2 2023 with final European Medicines Agency decision in second half of 2023

PARIS, FRANCE, 13 June 2023 – Ipsen (Euronext: IPN: ADR: IPSEY) today announced that the U.S. Food and Drug Administration (FDA) has approved Bylvay^® (odevixibat) for the treatment of cholestatic pruritus in patients from 12 months of age with Alagille syndrome (ALGS). Bylvay is a once-daily, non-systemic ileal bile acid transport inhibitor (IBATi) that acts locally in the small intestine and has minimal systemic exposure. Bylvay was approved as the first drug treatment option for patients living with cholestatic pruritus due to progressive familial intrahepatic cholestasis (PFIC) in the U.S., and for the treatment of PFIC in Europe, in 2021. Bylvay is immediately available via prescription for eligible ALGS patients.

“Today’s approval of Bylvay in a second indication allows patients and physicians to access an additional treatment option that has the potential to improve the management of pruritus, or intense itch, in this distressing condition that tends to affect young children,” said Howard Mayer, Executive Vice President and Head of Research and Development for Ipsen. “We are proud to have achieved FDA approval for Bylvay as a treatment for ALGS in the U.S. and we are committed to making it available to many more eligible patients across the world.”

Positive data from the Phase III ASSERT study, presented at the 2022 American Association for Study of Liver Diseases congress, demonstrated that Bylvay provided highly statistically significant and clinically meaningful sustained improvements in pruritus, starting early after initiation of treatment. More than 90% of patients were pruritus responders (≥ 1 point change at any time during 24 weeks). The overall incidence of treatment-emergent adverse events was similar to placebo. No patients discontinued the study and 96% of patients rolled over into the open-label extension study.

“Physicians urgently need more options to treat patients with Alagille syndrome and this approval from the U.S. FDA spotlights the robustness of the Phase III ASSERT clinical study results,” said Nadia Ovchinsky, MD, Chief of the Division of Gastroenterology and Hepatology, Hassenfeld Children’s Hospital at NYU Langone and ASSERT Principal Investigator. “The ASSERT study showed that Bylvay reduced pruritus associated with ALGS, which is so common among this patient population and one of the leading indications for a liver transplant.”

Roberta Smith, President, Alagille Syndrome Alliance said: “As an advocate for families impacted by Alagille syndrome, it is such a blessing to know physicians now have another drug treatment option for the debilitating pruritus that affects so many Alagille patients. I know personally the terrible impact of this rare disease on a child; this approval will help to alleviate the pruritus burden for more patients.”

Ipsen has also submitted Bylvay to the European Medicines Agency (EMA), seeking authorization for ALGS, with Committee for Medicinal Products for Human Use opinion expected in Q2 2023 and final EMA regulatory decision anticipated in second half of 2023. Bylvay has received orphan exclusivity for the treatment of PFIC, and Orphan Drug Designations for the treatment of ALGS and biliary atresia, in the U.S. and Europe. Bylvay is already approved in the U.S. for the treatment of pruritus in patients aged three months and older with all types of PFIC, and in Europe for the treatment of all types of PFIC in patients aged six months or older. In a third indication, the rare pediatric cholestatic liver disease, biliary atresia, Bylvay is in late-stage development with the Phase III BOLD trial.

ENDS

About Bylvay^® (odevixibat)

Bylvay is a potent, once-daily, non-systemic IBATi that acts locally in the small intestine and has minimal systemic exposure. It is approved in the U.S. for the treatment of pruritus in patients three months of age and older with PFIC, where it has orphan exclusivity. Bylvay was first launched as a treatment option for patients with PFIC in the U.S. in 2021, where it is supported by a program designed to assist with access to treatment and patient support. Bylvay is also approved in the E.U. for the treatment of PFIC in patients aged six months or older. It has launched in over nine countries and has secured public reimbursement across several major markets including Germany, Italy, the U.K., France and Belgium.

View full U.S. prescribing information here: Ipsen.com
View full E.U. prescribing information here: Bylvay, INN-odevixibat (europa.eu)

Important Safety Information 

• PFIC: The most common adverse reactions are diarrhea, liver test abnormalities, vomiting, abdominal pain, and fat-soluble vitamin deficiency. 
• ALGS: The most common adverse reactions are diarrhea, abdominal pain, hematoma, and weight decrease.
• Liver Test Abnormalities: Patients should obtain baseline liver tests and monitor during treatment. Dose reduction or treatment interruption may be required if abnormalities occur. For persistent or recurrent liver test abnormalities, consider treatment discontinuation.
• Diarrhea: Treat dehydration. Treatment interruption or discontinuation may be required for persistent diarrhea.
• Fat-Soluble Vitamin (FSV) Deficiency: Patient should obtain baseline vitamin levels and monitor during treatment. Supplement if deficiency is observed. If FSV deficiency persists or worsens despite FSV supplementation, discontinue treatment.

ALGS
ALGS is an inherited rare, genetic disorder that can affect multiple organ systems in the body including the liver, heart, skeleton, eyes and kidneys. Liver damage may result from having fewer than normal, narrowed or malformed bile ducts, which leads to toxic bile acid build-up, which in turn can cause scarring and progressive liver disease.¹ Approximately 95% of patients with the condition present with chronic cholestasis, usually within the first few months of life and as many as 88% also present with severe, intractable pruritus.^2,3 The estimated global incidence of ALGS is 3 in 100,000 live births.⁴ Currently in the U.S., it is estimated that there are 1,300 patients who may be eligible for IBATi treatment.

ASSERT Phase III Clinical Trial Data
ASSERT is a double-blind, randomized, placebo-controlled trial designed to evaluate the safety and efficacy of 120 µg /kg/day Bylvay for 24 weeks in relieving pruritus in patients with ALGS with 32 sites across North America, Europe, Middle East, and Asia Pacific. The trial enrolled patients aged 0 to 17 years of age with a genetically confirmed diagnosis of ALGS. In the primary analysis, the study met the primary endpoint showing highly statistically significant improvement in pruritus as measured by the PRUCISION Observer-Reported Outcome scratching score (0-4 point scale), from baseline at month 6 (weeks 21 to 24), compared to the placebo arm (p=0.002). More than 90% of patients were pruritus responders (≥ 1 point change at any time during 24 weeks). The study also met the key secondary endpoint showing a highly statistically significant reduction in serum bile acid concentration from baseline to the average of weeks 20 and 24 (compared to the placebo arm p=0.001). Statistically significant improvements in multiple sleep parameters were observed as early as weeks 1-4 compared to patients on placebo with continued improvement through week 24. In the study, there were no patient discontinuations and 96% of patients rolled over into the open-label extension study. Bylvay had an overall adverse event incidence similar to placebo and a low incidence of drug-related diarrhea (11.4% vs. 5.9% placebo).

About Ipsen 
Ipsen is a global, mid-sized biopharmaceutical company focused on transformative medicines in Oncology, Rare Disease and Neuroscience. With total sales of €3.0bn in FY 2022, Ipsen sells medicines in over 100 countries. Alongside its external-innovation strategy, the Company’s research and development efforts are focused on its innovative and differentiated technological platforms located in the heart of leading biotechnological and life-science hubs: Paris-Saclay, France; Oxford, U.K.; Cambridge, U.S.; Shanghai, China. Ipsen has around 5,400 colleagues worldwide and 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

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1. U.S. Department of Health and Human Services. Alagille syndrome- about the disease. Genetic and rare diseases information center. https://rare-diseases.info.nih.gov/diseases/804/alagille-syndrome
2. Singh S P.Euroasian J Hepatogastroenterol. 2018;8(2):140-147
3. Feldman A G. Neoreviews 2013;14 (2): e63–e73
4. Leonard L. European Journal of Human Genetics. 2014; 22:435

Attachment

• Ipsen PR_FDA Bylvay_13062023