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October 22, 2024

NICE recommends Ipsen’s IQIRVO® (elafibranor) – the first medicine approved for NHS use in nearly a decade for primary biliary cholangitis (PBC), a rare liver disease

  • Elafibranor is indicated 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 UDCA1
  • Elafibranor is a first-in-class treatment for primary biliary cholangitis (PBC) – associated with severe fatigue and persistent, debilitating itch1,2,3
  • PBC is a life-long condition that affects approximately 25,000 people in the U.K. – 9 in 10 of which are women4
  • If inadequately treated, PBC can worsen over time and cause liver failure, leading to liver transplant and in rare cases, premature death4,5,6

LONDON, U.K., 22 October, 2024 – Ipsen (Euronext: IPN; ADR: IPSEY) announced today that the National Institute for Health and Care Excellence (NICE) has recommended elafibranor 80mg tablets 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.7 This makes elafibranor the first medicine for PBC approved for use on the NHS in nearly a decade.7,8

Interim funding for elafibranor has been made available via the Innovative Medicines Fund (IMF), providing immediate access for eligible patients. Funding through the IMF will continue until NICE publishes its final Technology Appraisal, at which point elafibranor will be funded routinely by the NHS.

“This NICE approval represents an important step forward in the management of this potentially life-threatening rare liver condition.” commented Professor David Jones, Professor of Liver Immunology, Newcastle University. “This is particularly for those patients who may need an additional treatment option to slow the progression of the disease. The availability of a new therapeutic option on the NHS for PBC is welcome news for healthcare teams supporting patients with this debilitating and often misunderstood condition.”

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.4,5,6 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.2,3 This can potentially prevent an accurate and prompt diagnosis. PBC affects approximately nine women for every one man, with most patients potentially of menopausal age, around the ages of 40-60 years.4,9

“As a rare condition that primarily affects women around menopausal age, it is not uncommon for PBC to be diagnosed late or, in some cases, for these symptoms not to be taken seriously at all,” commented Mo Christie, Head of Patient Services at The PBC Foundation. “The availability of a new treatment option is a significant step forwards for people living with PBC and may help to raise awareness of the condition overall, leading to earlier diagnoses and improved disease management.”

PBC is a rare, autoimmune, cholestatic liver disease that impacts approximately 25,000 people in the U.K.4 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 ducts.6 While the causes of PBC are unknown, it is associated with genetic risks and environmental triggers.10

Elafibranor is a first-in-class, oral, once-daily peroxisome proliferator-activated receptor (PPAR) α/δ agonist.1,11 Activation of PPARα and PPARδ reduces bile toxicity, reduces inflammation and improves cholestasis.1

Today’s reimbursement decision for elafibranor is based on data from the Phase III ELATIVE trial published in the New England Journal of Medicine.11 In the ELATIVE trial 51% (55/108) of patients treated with elafibranor plus UDCA achieved the composite primary endpoint of cholestasis response* at week 52 compared to 4% (2/53) of patients in the placebo plus UDCA group.11

Secondary endpoints were normalisation of alkaline phosphatase (ALP) levels at week 52 and a change in pruritus intensity from baseline through week 52 and through week 24.11 The ELATIVE trial showed normalisation in ALP levels in only elafibranor-treated patients (15% for elafibranor plus UDCA (n=108) versus 0% for placebo plus UDCA (n=53)). A greater decrease in pruritus intensity, based on PBC Worst Itch Numeric Rating Scale (PBC WI-NRS), was observed in elafibranor-treated patients compared to placebo but this was not statistically significant.11

Additional patient-reported outcome measures were used to assess itch-related quality of life, including sleep and functioning, with greater improvements observed in patients treated with elafibranor compared to placebo.12 A post-hoc study of the ELATIVE trial found that 58% of patients receiving elafibranor reported less time itching (improved duration) compared with 27% on placebo at week 52,12 and 80% of patients receiving elafibranor reported reduced or no sleep disturbance compared with 30% on placebo.12

“NICE’s decision comes at a pivotal time as currently available treatments do not effectively manage both PBC disease progression and life-impacting symptoms like itch and sleep disturbances. This approval is an important step for us in improving outcomes for people living with PBC and further reinforces our commitment to addressing unmet medical needs in rare cholestatic liver diseases”, said Dr David Montgomery, U.K. & Ireland Medical Director at Ipsen.

Professor David Jones, Professor of Liver Immunology, Newcastle University, commented: “Research demonstrates the significant quality of life impact of PBC. As healthcare professionals, it is important we consider all aspects of the disease, beyond liver health alone.”

Elafibranor was generally well tolerated in the ELATIVE trial.11 Patients in the treatment group and the UDCA plus placebo group experienced similar percentages of adverse events, treatment-related adverse events, severe or serious adverse events or adverse events leading to discontinuation.11 Adverse events occurring in >10% of patients and more frequently on elafibranor versus placebo included abdominal pain (11%), diarrhoea (11%), nausea (11%), and vomiting (11%).11

*Cholestasis response is defined as ALP <1.67 × upper limit of normal (ULN), total bilirubin ≤ ULN, and ALP decrease ≥15%.11 ALP is a biochemical marker and is used as a surrogate endpoint in PBC trials.13

ENDS

About IQIRVO® (elafibranor)

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.7 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.1 Activation of PPARα and PPARδ also has anti-inflammatory effects by acting on different pathways.1 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.14 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 the Phase III ELATIVE trial

ELATIVE is a multinational, randomised double-blind, placebo-controlled Phase III clinical trial (n=161) that evaluated the efficacy and safety of elafibranor 80mg once daily plus UDCA (n=108) versus placebo plus UDCA (n=53). Elafibranor or placebo was administered in combination with UDCA in 95% of patients and as monotherapy in 5% of patients who were unable to tolerate UDCA. The results were published in the New England Journal of Medicine.11

  • The ELATIVE trial demonstrated that elafibranor had a statistically significant treatment benefit with 51% (n=55/108) of patients on elafibranor achieving a cholestasis response compared with 4% (n=2/53) on the placebo arm, a placebo-adjusted treatment effect of 47% (95% CI 32, 57; p<0.0001). Cholestasis response was defined as ALP less than 1.67 ULN, an ALP decrease of greater than or equal to 15% from baseline and total bilirubin (TB) ≤ ULN at week 52.11
  • The significant cholestasis response to elafibranor was further supported by data demonstrating reductions from baseline in ALP levels were sustained through week 52 and response was rapid, seen as early as week 4 in the elafibranor group.11
  • ALP normalisation at week 52 was a key secondary endpoint with 15% (n=16/108) of elafibranor-treated patients demonstrating normalisation versus 0% placebo (95% CI 6, 23; p=0.002).11
  • While elafibranor showed an observed improvement in pruritus change from baseline based on PBC Worst Itch Numeric Rating Scale score compared to placebo, the result was not statistically significant.11
  • Additional patient-reported outcome measures (5-D itch and PBC-40 itch) were used to assess itch-related quality of life, including sleep and functioning, with greater improvements observed in patients treated with elafibranor compared to placebo.12
    • 58% (n=14/24) of patients receiving elafibranor reported less time itching (improved duration) compared with 27% on placebo at week 52.12
    • 80% (n=20/25) of patients receiving elafibranor reported reduced or no sleep disturbance compared with 30% on placebo.12
  • The most common adverse reactions with elafibranor reported in ≥10% of study participants were abdominal pain (11%), diarrhoea (11%), nausea (11%) and vomiting (11%).11

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 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.

Ipsen contacts

Sam Howland, Head of Communications, U.K & Ireland | sam.howland@ipsen.com

External organisation media contacts

Charlotte Worrall, 90TEN Communications | charlotte.worrall@90ten.co.uk
Fi Warren, 90TEN Communications | fi.warren@90ten.co.uk

 

IQV-GB-000008 | October 2024

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 favourable 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 authorisation or that the medicine will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialise, 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 authorisation; 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. Summary of Product Characteristics. IQIRVO. Available at: https://mhraproducts4853.blob.core.windows.net/docs/b73c18660ce726aae8769acec38094cf004ff2f2. Last accessed: October  2024.
  2. Mells GF, et al. 2013. Impact of Primary Biliary Cholangitis on Perceived Quality of Life: The UK-PBC National Study. Hepatology. 58: 273-283.
  3. 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.
  4. 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.
  5. NHS Blood and Transplant. Annual Report of Liver Transplantation Report for 2020/2021. Published 2021.
  6. Younossi ZM, et al. 2019. Diagnosis and Management of Primary Biliary Cholangitis. Am J Gastroenterol. 114(1):48–63
  7. National Institution for Health and Care Excellence. Elafibranor for treating primary biliary cholangitis. Available at: https://www.nice.org.uk/guidance/indevelopment/gid-ta11378/documents. Last accessed: October 2024.
  8. 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: October 2024.
  9. Trivella J, et al. Primary biliary cholangitis: Epidemiology, prognosis, and treatment. Hepatol Commun. 2023 Jun; 7(6): e0179.
  10. Gulamhusein AF, et al. Primary Biliary Cholangitis, DNA and Beyond: The Relative Contribution of Genes. Hepatology. 2018 Jul; 68(1): 19–21.
  11. Kowdley. K.V, et al. Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis. NEJM. 2023. DOI: 10.1056/NEJMoa2306185.
  12. Kremer AE, et al. 2024. Effect of elafibranor on pruritus in primary biliary cholangitis: Symptom severity and quality of life measurements from the phase III ELATIVE® trial. Journal of Hepatology Abstract Book. VOLUME 80 Suppl. 1 JUNE 2024. Available at: https://www.easlcongress.eu/wp-content/uploads/2024/06/Updated-1-EASL_2024_Abstract_version3-1.pdf Last accessed: October 2024.
  13. EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis Journal of Hepatology 2017 vol. 67 j 145–172.
  14. MHRA. Elafibranor approved as first medicine 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: October 2024.

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