Iqirvo® (elafibranor) data show efficacy and tolerability for up to 3 years in patients with PBC with improvements in fatigue and pruritus

• Ipsen presents three late-breaking presentations and eight abstracts across rare cholestatic liver disease portfolio at AASLD 2024
• Elafibranor was granted marketing authorisation for the treatment of primary biliary cholangitis (PBC) by the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) in October 2024¹
• The new data comes as the National Institute for Health and Care Excellence (NICE) recommended elafibranor for the treatment of PBC, with final guidance issued on Thursday 14 November 2024²

LONDON, U.K., 18 November 2024 Ipsen (Euronext: IPN; ADR: IPSEY) announced today late-breaking data for Iqirvo^® (elafibranor 80 mg tablets) from an interim analysis of the ongoing open-label extension of the Phase III ELATIVE^® study at the American Association for the Study of Liver Disease (AASLD) congress. The late-breaking presentations (Abstract #5041 and Abstract #5042) report on biomarkers of cholestasis, stabilisation of surrogate markers of liver fibrosis and moderate-to-severe pruritus data for up to three years in elafibranor-treated patients.³ Additionally, exploratory endpoints in fatigue and sleep were evaluated using patient-reported outcomes tools.⁴

The release of this new data closely follows the final guidance of elafibranor for the treatment of PBC in England, published by NICE on Thursday 14 November.² Elafibranor 80mg tablets were recommended for the treatment of PBC in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA, making it the first new medicine for PBC approved for use on the NHS in nearly a decade.^2,5

“Over three years, elafibranor data suggest sustained efficacy and support the safety profile of the medicine. Importantly, when patients tell me they are less impacted by itch and fatigue—that matters to me as a physician,” said Dr. Kris Kowdley, Director at The Liver Institute Northwest, Washington and a primary investigator on the ELATIVE study. “Treatment with elafibranor had an impact on symptoms of pruritus and surrogate markers of fibrosis, which are important findings for people living with PBC.”

“Severe fatigue is a symptom often reported by people living with PBC and can have a really debilitating impact on their lives,” said Professor David Jones, Professor of Liver Immunology, Newcastle University. "Patients treated with elafibranor reported improvement in their sleep and fatigue, across several patient-reported outcome measures. The links between itch, sleep disturbance and fatigue are thought to be really important in PBC and offer a real opportunity for treatment”

The open-label extension (OLE) included 138 patients who completed the double-blind period of the Phase III ELATIVE^® study.3 This interim analysis was performed after at least one year of treatment with elafibranor in the OLE (up to three years total).³ Results have been presented descriptively. In patients receiving three years of continuous treatment with elafibranor across the double-blind period and OLE (n=13), 85% had a cholestasis response* (n=11/13; ALP <1.67 x ULN, with ≥ 15% reduction from baseline and total bilirubin ≤ ULN) and 39% achieved ALP normalisation (n=5/13) at week 156.³ Surrogate markers of liver fibrosis, liver stiffness measurements (n=23) and enhanced liver fibrosis (ELF™) (n=19) scores, suggest stabilisation when measured from baseline to week 130.³ In patients continuously receiving elafibranor for up to 156 weeks, pruritus improvements were sustained for patients with moderate or severe pruritus at baseline (n=5).³

No new safety findings were observed.³ The most common treatment-emergent adverse events (>10%) occurring more frequently in patients treated with elafibranor than placebo in the double-blind period of the trial (abdominal pain (11%), diarrhoea (11%), nausea (11%) and vomiting (11%)) were also reported in the OLE.⁶

The impact of elafibranor on fatigue and sleep were also investigated as an exploratory endpoint in the OLE.⁴ Changes in fatigue or sleepiness (including normal sleep) were reviewed from baseline to week 104 looking at the minimal clinically important differences and categorical changes (n=48).⁴ Fatigue and sleep improvements for patients treated with elafibranor were observed at week 104 across three patient reported outcome (PRO) tools.⁴ In patients with moderate-to-severe fatigue or excessive sleepiness at baseline, clinically meaningful improvements were observed after 104 weeks of treatment with elafibranor in 56% (n=18) of patients according to the PRO Measurement Information System (PROMIS) Fatigue Short Form 7a, 50% (n=24) of patients according to the fatigue domain of the PBC-40, and 69% (n=16) of patients according to the Epworth Sleepiness Scale (ESS).⁴ These are interim data and have not been submitted to regulatory agencies.⁴ A confirmatory study of elafibranor is ongoing (NCT06016842).

“People living with PBC tell us just how devastating this disease can be for patients and their families,” said Dr David Montgomery, U.K. & Ireland Medical Director at Ipsen. “Following the recommendation for elafibranor by NICE, who just last week published its final guidance, this new data provides a timely reminder of the importance of this new treatment option for those eligible to receive it. Ipsen is committed to continuing its efforts to ensure access to elafibranor for all eligible patients across the U.K.”

*Cholestasis response is defined as ALP <1.67 × upper limit of normal (ULN), total bilirubin ≤ ULN, and ALP decrease ≥15%.⁶ ALP is a biochemical marker and is used as a surrogate endpoint in PBC trials.⁷

About PBC

PBC is a rare, autoimmune, cholestatic liver disease that impacts approximately 25,000 people in the U.K.⁸ It affects approximately nine women for every one man, with most patients potentially of menopausal age, around the ages of 40-60 years.^8,9 The disease causes a build-up of bile and toxins (cholestasis) and chronic inflammation, leading to irreversible fibrosis (scarring) of the liver and destruction of the bile duct.¹⁰

PBC is a lifelong condition that can worsen over time if inadequately treated, causing liver failure, leading to liver transplant and in rare cases, premature death.^8,10,11 Despite the critical impact of the disease in its advanced stages, people with PBC in its earlier stages commonly experience severe fatigue and a persistent, debilitating itch, known as pruritus.^12,13

About Iqirvo^® (elafibranor) 80 mg tablet

IQIRVO^® – pronounced EYE-KER-VO – (elafibranor) is an oral, once-daily, peroxisome proliferator-activated receptor (PPAR) agonist. It is indicated for the treatment of PBC in combination with UDCA in adults with an inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA.² Elafibranor exerts an effect on PPARα and PPARδ. Activation of PPARα and PPARδ decreases bile toxicity and improves cholestasis by modulating bile acid synthesis, detoxification and transporters.¹⁴ Activation of PPARα and PPARδ also has anti-inflammatory effects by acting on different pathways.¹⁴ In October 2024, elafibranor was licensed for the treatment of PBC in combination with UDCA in adults with an inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA, in the in the UK.¹ Elafibranor was discovered and developed by GENFIT and Ipsen licensed the exclusive worldwide rights (except China, Hong Kong, Taiwan and Macau) to elafibranor from GENFIT in 2021.

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 80 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.

Disclaimers and/or Forward-Looking Statements

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¹ Medicines and Healthcare products Regulatory Agency. Elafibranor approved to treat adults with a rare liver disease known as primary biliary cholangitis. Available at: https://www.gov.uk/government/news/elafibranor-approved-as-first-medicine-to-treat-adults-with-a-rare-liver-disease-known-as-primary-biliary-cholangitis. Last accessed: November 2024.

² National Institution for Health and Care Excellence. Elafibranor for treating primary biliary cholangitis. Available at: https://www.nice.org.uk/guidance/indevelopment/gid-ta11378. Last accessed: November 2024.

³ Kowdley. K. et al. 2024. Long term efficacy and safety of elafibranor in primary biliary cholangitis:

Interim results from the open-label extension of the ELATIVE® trial up to 3 years. Poster, Abstract 5041. American Association for the Study of Liver Disease (AASLD), 15-19 November 2024, San Diego.

⁴ Swain M, et al. 2024. Impact of elafibranor on fatigue in patients with primary biliary cholangitis:

Interim results from the long-term open-label extension of the ELATIVE® trial. Poster, Abstract 5042. American Association for the Study of Liver Disease (AASLD), 15-19 November 2024, San Diego.

⁵ NICE. Obeticholic acid for treating primary biliary cholangitis. Technology appraisal guidance. Available at: https://www.nice.org.uk/guidance/ta443/resources/obeticholic-acid-for-treating-primary-biliary-cholangitis-pdf-82604782944709. Last accessed: November 2024.

⁶ Kowdley. K.V, et al. Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis. NEJM. 2023. DOI: 10.1056/NEJMoa2306185.

⁷ EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis Journal of Hepatology 2017 vol. 67 j 145–172.

⁸ Webb GJ, Ryan RP, Marshall TP, Hirschfield GM. The Epidemiology of UK Autoimmune Liver Disease Varies With Geographic Latitude. Clin Gastroenterol Hepatol. 2021 Dec;19(12):2587-2596. doi: 10.1016/j.cgh.2021.01.029. Epub 2021 Jan 22. PMID: 33493696; PMCID: PMC8661127.

⁹ Trivella J, et al. Primary biliary cholangitis: Epidemiology, prognosis, and treatment. Hepatol Commun. 2023 Jun; 7(6): e0179.

¹⁰ Younossi ZM, et al. 2019. Diagnosis and Management of Primary Biliary Cholangitis. Am J Gastroenterol. 114(1):48–63.

¹¹ NHS Blood and Transplant. Annual Report of Liver Transplantation Report for 2020/2021. Published 2021.

¹² Mells GF, et al. 2013. Impact of Primary Biliary Cholangitis on Perceived Quality of Life: The UK-PBC National Study. Hepatology. 58: 273-283.

¹³ C Levy, et al. 2023. Understanding the Experience of Patients with Primary Biliary Cholangitis and Pruritus. Abstract presented at ISPOR, 7-11 May 2023, Boston.

¹⁴ Summary of Product Characteristics. IQIRVO. Available at: https://mhraproducts4853.blob.core.windows.net/docs/b73c18660ce726aae8769acec38094cf004ff2f2. Last accessed: November 2024.

IQV-GB-000041 | November 2024