Ipsen 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. This makes elafibranor the first medicine for PBC approved for use on the NHS in nearly a decade.
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. 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. 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.
“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. 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. While the causes of PBC are unknown, it is associated with genetic risks and environmental triggers.
Elafibranor is a first-in-class, oral, once-daily peroxisome proliferator-activated receptor (PPAR) α/δ agonist. Activation of PPARα and PPARδ reduces bile toxicity, reduces inflammation and improves cholestasis.
Today’s reimbursement decision for elafibranor is based on data from the Phase III ELATIVE trial published in the New England Journal of Medicine. 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.
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. The ELATIVE trial showed normalization 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.
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. 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, and 80% of patients receiving elafibranor reported reduced or no sleep disturbance compared with 30% on placebo.
“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.
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.”
Professor David Jones, Professor of Liver Immunology, Newcastle University
Elafibranor was generally well tolerated in the ELATIVE trial. 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. 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%).
