U.K. MHRA grants marketing authorisation for Ipsen’s Iqirvo® (elafibranor), a first-in-class peroxisome proliferator-activated receptor (PPAR) treatment for primary biliary cholangitis (PBC)

• 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 the first medicine granted marketing authorisation in nearly a decade for the treatment of PBC – a rare liver disease^2,3
• PBC impacts approximately 25,000 people in the U.K. and is growing in global prevalence.⁴ If inadequately treated, it can cause liver failure and, in some cases, the need for transplantation^4,5
• Marketing authorisation is based on positive Phase III ELATIVE trial data⁶

LONDON, U.K., 8 October, 2024 – Ipsen (Euronext: IPN; ADR: IPSEY) announced today that the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorisation for elafibranor 80mg tablets 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.^1,3 Elafibranor has been submitted for review by the National Institute for Health and Care Excellence (NICE), with a decision expected later in 2024.

PBC is a rare, autoimmune, cholestatic liver disease where a build-up of bile and toxins (cholestasis) and chronic inflammation causes irreversible fibrosis (scarring) of the liver and destruction of the bile ducts.⁷ A lifelong condition that can worsen over time if not effectively treated,⁷ it is thought to affect approximately 25,000 people in the U.K., the majority being women.⁴ In 2021, the disease accounted for approximately one-tenth of liver transplant activity in the U.K., and in rare cases can lead to death.^4,5 Those living with the condition can often face significant symptoms which impact their day-to-day life, with people most commonly experiencing severe fatigue and persistent, debilitating itch (pruritus).^8,9

“There are many people living with PBC with their needs unmet – be that markers of their disease worsening or symptom burden not being controlled. This can have profound implications for patients and their families, which is why a new treatment option is so vitally important.” said Mo Christie, Head of Patient Services, PBC Foundation.

Elafibranor is a first-in-class, oral, once-daily dual peroxisome proliferator-activated receptor (PPAR) α/δ agonist.^6,1 Activation of PPARα and PPARδ reduces bile toxicity, reduces inflammation and improves cholestasis.¹

The MHRA’s marketing authorisation for elafibranor is based on data from the Phase III ELATIVE trial published in the New England Journal of Medicine.⁶ The ELATIVE trial evaluated the safety and efficacy of elafibranor 80mg in 161 people living with PBC who have an inadequate response or intolerance to the current standard of care, ursodeoxycholic acid (UDCA), at risk of disease progression. Most patients (95%) received study treatment (elafibranor or placebo) in combination with UDCA.⁶

In the 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.⁶ Cholestasis response is defined as alkaline phosphatase (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 clinical trial outcomes.¹⁰ ALP and bilirubin are important predictors of the disease progression.⁶

Secondary endpoints were normalisation of the ALP level at week 52 and a change in pruritus intensity from baseline through week 52 and through week 24.⁶ 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)).⁶ 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.⁶

The most common adverse reactions with elafibranor, reported in ≥10% of study participants, were abdominal pain (11%), diarrhoea (11%) nausea (11%) and vomiting (11%).⁶ The majority of adverse events were of mild to moderate intensity.⁶

“Elafibranor is the first medicine for PBC in nearly a decade, offering a promising new treatment option for people living with this rare condition. This is especially significant for those who may need an additional option beyond current first-line treatments. The MHRA’s decision represents real progress and we’re now committed to working with the National Institute of Health and Care Excellence (NICE) to obtain reimbursement and ensure people living with PBC who are eligible can access elafibranor”, said Dr David Montgomery, U.K. & Ireland Medical Director at Ipsen.

Elafibranor is currently undergoing review by NICE and a decision is anticipated later in 2024. It has also been granted conditional marketing authorisation by the European Medicines Agency (EMA), following a positive opinion from their Committee for Medicinal Products for Human Use (CHMP) in July.

ENDS

About Iqirvo^® (elafibranor)

The detailed recommendations for the use of Iqirvo^® (elafibranor) are described in the Summary of Product Characteristics (SmPC) from the Medicines and Healthcare products Regulatory Agency.

Elafibranor is an oral, once-daily, peroxisome proliferator-activated receptor (PPAR) agonist 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. 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. Activation of PPARα and PPARδ also has anti-inflammatory effects by acting on different pathways. Elafibranor is currently undergoing review by NICE and was granted conditional marketing authorisation by the EMA. Elafibranor was developed by GENFIT. Ipsen licensed the exclusive worldwide rights (except China, Hong Kong, Taiwan and Macau).

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.⁶

• 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<0.001). Cholestasis response was defined as ALP less than 1.67 x Upper Limit of Normal (ULN), an ALP decrease of greater than or equal to 15% from baseline and total bilirubin (TB) ≤ ULN at week 52.⁶
• ALP normalisation at week 52 was a key secondary endpoint, with 15% (n=16/108) of elafibranor-treated patients demonstrating normalisation versus 0% on placebo (95% CI 6, 23; p=0.002).⁶
• 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.⁶
• 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.⁶
• 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.¹¹
  • 58% (n=14/24) of patients receiving elafibranor reported less time itching (improved duration) compared with 27% on placebo at week 52.¹¹
  • 80% (n=20/25) of patients receiving elafibranor reported reduced or no sleep disturbance compared with 30% on placebo.¹¹
• The most common adverse reactions with elafibranor, reported in ≥10% of study participants, were abdominal pain (11%), diarrhoea (11%), nausea (11%) and vomiting (11%).⁶

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

 

ELA-UK-000074 | October 2024

Disclaimers and/or Forward-Looking Statements

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 upon request.
2. 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.
3. 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.
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. Kowdley. K.V, et al. Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis. NEJM. 2023. DOI: 10.1056/NEJMoa2306185.
7. Younossi ZM, et al. 2019. Diagnosis and Management of Primary Biliary Cholangitis. Am J Gastroenterol. 114(1):48–63
8. Mells GF, et al. 2013. Impact of Primary Biliary Cholangitis on Perceived Quality of Life: The UK-PBC National Study. Hepatology. 58: 273-283.
9. 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.
10. EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis Journal of Hepatology 2017 vol. 67 j 145–172.
11. 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.