Ipsen’s Kayfanda® (odevixibat) approved in European Union for cholestatic pruritus in Alagille Syndrome, a rare liver disease | 23.09.24

• Kayfanda^® (odevixibat) approved as new treatment choice for cholestatic pruritus in children from six months with the rare liver condition, Alagille Syndrome
• E.U. marketing authorization for Kayfanda based on data from ASSERT the only Phase III trial completed in patients with Alagille Syndrome
• Kayfanda approval for use in the E.U. further expands Ipsen’s rare cholestatic liver disease portfolio

PARIS, FRANCE, xx September, 2024 Ipsen (Euronext: IPN; ADR: IPSEY) today announced that the European Commission has approved Kayfanda^® (odevixibat) under exceptional circumstances for the treatment of cholestatic pruritus in Alagille Syndrome (ALGS) in patients aged 6 months or older. Kayfanda is a once-daily non-systemic ileal bile acid transport (IBAT) inhibitor. Odevixibat, the active substance in Kayfanda, blocks the ileal bile acid transporter (IBAT), which ultimately results in a decrease in serum bile acids that can form in the liver.

”Patients living with Alagille syndrome often endure a very poor quality of life as a result of the intolerable itch, which is one of the most significant symptoms of this condition,” said Christelle Huguet, Executive Vice President and Head of Research and Development, Ipsen. “Today’s decision is therefore very welcome. We will now continue in our ongoing efforts to make this new treatment option available for use with patients living in the E.U.”

Approval of Kayfanda, known in ALGS as Bylvay^® outside of the E.U., was based on the ASSERT Phase III clinical trial data.¹ ASSERT is the world’s first and only Phase III trial completed in patients with ALGS. These data demonstrated statistically significant and clinically meaningful improvements from baseline to month 6 in scratching severity for patients on Kayfanda versus placebo. This was observed rapidly and maintained over the period of the study. A statistically significant reduction in serum bile acid concentration at the end of treatment was also demonstrated for patients on Kayfanda versus placebo, with improvements in multiple observer-reported sleep parameters. The overall incidence of treatment emergent adverse events with Kayfanda was similar to placebo, with a low drug-related diarrhea rate in patients with ALGS.

“ALGS is a distressing condition, which often presents in the first few months of life. One of the most common symptoms reported, as a result of the condition, is severe pruritus, with children scratching to the point of bleeding and the itch causing sleep disturbances for the child and their carers,” said Professor Henkjan Verkade, Pediatric Gastroenterology and Hepatology, Department of Pediatrics, University of Groningen, Beatrix Children’s Hospital and University Medical Center Groningen, Netherlands. “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.”

ALGS is an inherited rare, genetic disorder that can affect multiple organs 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 a build-up of toxic bile acid, known as cholestasis and this in turn can cause fibrosis and progressive liver disease. 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. The estimated global incidence of ALGS is 3 in 100,000 live births.

Ipsen has also received E.U. approval for Iqirvo^® (elafibranor) for Primary Biliary Cholangitis, another important treatment in the company’s leading rare cholestatic liver disease portfolio.

Kayfanda is known in ALGS as Bylvay^® outside of the European Union (E.U.). Under the brand name of Bylvay it was approved in the E.U. as the first drug treatment option for all types of progressive familial intrahepatic cholestasis (PFIC) in patients aged 6 months or older. The medicine is also currently being studied in a Phase III trial, BOLD, in Biliary Atresia with data anticipated in 2026.

ENDS

About Kayfanda^® (odevixibat)
Kaydanda^® (odevixibat) is a once-daily non-systemic ileal bile acid transport (IBAT) inhibitor approved under exceptional circumstances in the E.U. for the treatment of cholestatic pruritus in Alagille syndrome (ALGS) in patients aged 6 months or older. Odevixibat was approved in June 2021 in the E.U. under the brand name Bylvay^®, 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 U.S. under the brand name Bylvay^®, 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 E.U. and in the U.S. 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.

About ASSERT
ASSERT is a double-blind, randomized, placebo-controlled trial designed to evaluate the safety and efficacy of 120 µg /kg/day odevixibat 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. Odevixibat had an overall adverse event incidence similar to placebo and a low incidence of drug-related diarrhea (11.4% vs. 5.9% placebo). ¹

Full results of the ASSERT study have been published in the Lancet, Gastroenterology & Hepatology in April 2024,

Important safety information and recommendations for the use of Kayfanda will be detailed in the Summary of Product Characteristics (SmPC), published in the European public assessment report (EPAR) and available in all official EU languages. The full SmPC will be found at: http://www.ema.europa.eu 

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 fuelled 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 contacts

Investors

• Craig Marks | + 44 (0)7584 34 91 93 | [email protected]
• Nicolas Bogler | + 33 6 52 19 98 92 | [email protected]

Media

• Anna Gibbins | + 44 7717 80 19 00| [email protected]

Disclaimers and/or Forward-Looking Statements

Ipsen

The forward-looking statements, objectives and targets contained herein are based on Ipsen’s management strategy, current views and assumptions. Such statements involve known and unknown risks and uncertainties that may cause actual results, performance or events to differ materially from those anticipated herein. All of the above risks could affect Ipsen’s future ability to achieve its financial targets, which were set assuming reasonable macroeconomic conditions based on the information available today. Use of the words ‘believes’, ‘anticipates’ and ‘expects’ and similar expressions are intended to identify forward-looking statements, including Ipsen’s expectations regarding future events, including regulatory filings and determinations. Moreover, the targets described in this document were prepared without taking into account external-growth assumptions and potential future acquisitions, which may alter these parameters. These objectives are based on data and assumptions regarded as reasonable by Ipsen. These targets depend on conditions or facts likely to happen in the future, and not exclusively on historical data. Actual results may depart significantly from these targets given the occurrence of certain risks and uncertainties, notably the fact that a promising medicine in early development phase or clinical trial may end up never being launched on the market or reaching its commercial targets, notably for regulatory or competition reasons. Ipsen must face or might face competition from generic medicine that might translate into a loss of market share. Furthermore, the research and development process involves several stages each of which involves the substantial risk that Ipsen may fail to achieve its objectives and be forced to abandon its efforts with regards to a medicine in which it has invested significant sums. Therefore, Ipsen cannot be certain that favorable results obtained during preclinical trials will be confirmed subsequently during clinical trials, or that the results of clinical trials will be sufficient to demonstrate the safe and effective nature of the medicine concerned. There can be no guarantees a medicine will receive the necessary regulatory approvals or that the medicine will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Other risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and healthcare legislation; global trends toward healthcare cost containment; technological advances, new medicine and patents attained by competitors; challenges inherent in new-medicine development, including obtaining regulatory approval; Ipsen’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Ipsen’s patents and other protections for innovative medicines; and the exposure to litigation, including patent litigation, and/or regulatory actions. Ipsen also depends on third parties to develop and market some of its medicines which could potentially generate substantial royalties; these partners could behave in such ways which could cause damage to Ipsen’s activities and financial results. Ipsen cannot be certain that its partners will fulfil their obligations. It might be unable to obtain any benefit from those agreements. A default by any of Ipsen’s partners could generate lower revenues than expected. Such situations could have a negative impact on Ipsen’s business, financial position or performance. Ipsen expressly disclaims any obligation or undertaking to update or revise any forward-looking statements, targets or estimates contained in this press release to reflect any change in events, conditions, assumptions or circumstances on which any such statements are based, unless so required by applicable law. Ipsen’s business is subject to the risk factors outlined in its registration documents filed with the French Autorité des Marchés Financiers. The risks and uncertainties set out are not exhaustive and the reader is advised to refer to Ipsen’s latest Universal Registration Document, available on ipsen.com.

References

1. Ovchinsky N., et al. Efficacy and safety of odevixibat in patients with Alagille syndrome (ASSRT); a phase 3, double-blind, randomized, placebo-controlled trial. Lancet Gastroenterol / Hepatol. 2024 doi.org/10.1016/S2468-1253(24)00074-8

• 
  Ipsen PR_Kayfanda ALGS EC decision_230924