Elafibranor for primary biliary cholangitis

Background:
Primary biliary cholangitis (PBC) is a chronic, progressive autoimmune liver disease characterised by the destruction of intrahepatic bile ducts, leading to cholestasis (impaired bile flow), inflammation and fibrosis. It can eventually progress to cirrhosis, liver failure and death. PBC occurs predominantly in women aged 40 years or older.¹

Ursodeoxycholic acid (also known as UDCA) is the standard first-line treatment for PBC; however, up to 40% of patients have an inadequate response and require add-on or second-line therapy (e.g. obeticholic acid).¹ Elafibranor provides a new add-on and second-line treatment option for adults with PBC.

Mechanism of action:
Elafibranor is a dual peroxisome proliferator–activated receptor (PPAR) agonist that activates both PPAR-alpha and PPAR-delta, which are key regulators of bile acid homeostasis, inflammation and fibrosis. Activation of these receptors decreases bile acid toxicity and subsequent injury to cholangiocytes, thereby improving cholestasis.^1,2

Clinical trials:
Elafibranor was evaluated in a phase 3 randomised controlled trial (ELATIVE) in adults with PBC aged 18 to 75 years who had an inadequate response to, or were unable to tolerate, ursodeoxycholic acid. Patients were eligible if they had an alkaline phosphatase concentration (ALP) of at least 1.67 times the upper limit of normal (175 units/L for women and 215 units/L for men) and a total bilirubin concentration no more than twice the upper limit of normal (41 micromoles/L). Patients with significant hepatic decompensation or autoimmune hepatitis were excluded.¹

Patients were randomised to receive elafibranor 80 mg (n=108) or placebo (n=53) once daily; 96% of patients were female and their mean age was 57 years. Treatment was continued for 52 to 104 weeks. Patients either received the study treatment in combination with ursodeoxycholic acid (95%) or as monotherapy if unable to tolerate ursodeoxycholic acid (5%). Patients who were receiving ursodeoxycholic acid before the study continued it at their pre-study dose.¹

The primary endpoint was a biochemical response at week 52, defined as an ALP concentration less than 1.67 times the upper limit of normal with at least a 15% reduction from baseline, and a total bilirubin concentration below the upper limit of normal. A greater proportion of patients in the elafibranor group demonstrated a biochemical response compared with the placebo group (51% versus 4%). This response occurred within 4 weeks after starting treatment and was maintained through 52 weeks. Among patients with moderate to severe pruritus at baseline, there was no significant difference in the change in pruritus intensity between the 2 groups over 52 weeks.¹

Adverse effects:
Adverse effects that occurred more frequently with elafibranor than placebo included abdominal pain (11% versus 6%), diarrhoea (11% versus 9%), nausea (11% versus 6%) and vomiting (11% versus 2%).¹ These events were mild to moderate in severity.

Four out of 108 patients discontinued elafibranor due to clinically significant elevations in creatine kinase. Of these, 2 were receiving concomitant statin therapy, one had coexisting chronic kidney disease and one had coexisting autoimmune thyroiditis. An additional patient who was receiving elafibranor and concomitant atorvastatin 40 mg developed rhabdomyolysis.¹

Dosage and administration:
Elafibranor is taken orally at a dose of 80 mg once daily, with or without food.

Dose adjustments are not required in renal impairment or mild or moderate hepatic impairment.

Precautions:
Elafibranor is not recommended in severe hepatic impairment or decompensated liver disease.

Use in pregnancy and breastfeeding:
Animal studies have demonstrated fetal harm; therefore, elafibranor is not recommended during pregnancy or in women of childbearing potential not using effective contraception. Elafibranor is not recommended during breastfeeding.²

Place in therapy:
Elafibranor may be used in place of ursodeoxycholic acid in patients who cannot tolerate it, or as an alternative to bezafibrate for add-on therapy with ursodeoxycholic acid. Bezafibrate, a pan-PPAR agonist, has been used for PBC and has more long-term real-world data; however, it is not commercially available in Australia (though it can be sourced via the Special Access Scheme).

Obeticholic acid was one of the first second-line drugs approved for PBC but has largely been superseded by PPAR agonists as preferred second-line therapy in Australia because of safety concerns and worsening pruritus.³

In clinical trials, elafibranor treatment did not reduce pruritus, so patients with bothersome pruritus may require additional symptomatic treatment,⁴ or bezafibrate may be considered.

An open-label extension study of the phase 3 ELATIVE trial is ongoing to assess the longer term safety and efficacy of elafibranor (up to 3.5 years).⁵

Other PPAR-targeted therapies for PBC are emerging. In January 2026, seladelpar (a selective PPAR-delta agonist) was registered in Australia for the same indication as elafibranor.⁶ Saroglitazar (a dual PPAR-alpha and PPAR-gamma agonist) is in clinical trials.⁷

Practice points:
Elafibranor should be prescribed by, or in consultation with, a gastroenterologist or hepatologist.⁸

Pregnancy should be excluded before starting treatment. Women of childbearing potential should use effective contraception during treatment and for 3 weeks after the final elafibranor dose.

Liver function tests should be performed before starting elafibranor and during treatment as clinically indicated. Creatine kinase should be measured before starting treatment; periodic creatine kinase monitoring may be considered in patients receiving concomitant statin therapy. Patients should be advised to report unexplained muscle symptoms.

This new drug comment was finalised on 19 June 2026. It was prepared by Sherilyn Wong, Clinical Editor, Australian Prescriber, and reviewed by Reeham Abu-Rgeef, Gastroenterology Specialist Pharmacist, Royal Perth Bentley Group, East Metropolitan Health Service, Western Australia.

At the time this new drug comment was prepared, the Australian Public Assessment Report was available from the Therapeutic Goods Administration. The sponsor did not provide the Clinical Evaluation Report.

This article is peer reviewed.

 

References

1. Kowdley KV, Bowlus CL, Levy C, Akarca US, Alvares-da-Silva MR, Andreone P, et al. Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis. N Engl J Med 2024;390:795–805.
2. Therapeutic Goods Administration. Australian Product Information – IQIRVO elafibranor film-coated tablets. Department of Health, Disability and Ageing; 2025. [cited 2026 Apr 28]
3. Nevens F, Andreone P, Mazzella G, Strasser SI, Bowlus C, Invernizzi P, et al. A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis. N Engl J Med 2016;375:631–43.
4. Martins A, Khakoo NS, Corpechot C, Rousseau A, Reynolds JM, Kremer AE, et al. Meta-Analysis: PPAR Agonists for Pruritus and Quality of Life in Primary Biliary Cholangitis. Aliment Pharmacol Ther 2026;63:1190–200.
5. ClinicalTrials.gov. A Long-Term Study of Elafibranor in Adult Participants With Primary Biliary Cholangitis (ELFIDENCE). Identifier NCT06016842. National Library of Medicine (US); 2026. [cited 2026 Apr 28]
6. Therapeutic Goods Administration. Livdelzi (seladelpar). Department of Health, Disability and Ageing; 2026. [cited 2026 Apr 28]
7. ClinicalTrials.gov. Study of Saroglitazar Magnesium for PBC Patients With Incomplete Response or Intolerant to UDCA Therapy (EPICS-IV). Identifier NCT07424677. National Library of Medicine (US); 2026. [cited 2026 Apr 28]
8. Pharmaceutical Benefits Scheme. Elafibranor. Department of Health, Disability and Ageing; 2025. [cited 2026 Apr 28]

 

The new drug comments in Australian Prescriber are prepared by the editors and reviewed by subject matter experts. Some of the views expressed on newly approved products should be regarded as preliminary, as there may be limited published data at the time of publication, and little experience in Australia of their safety or efficacy. Before new drugs are prescribed, it is important that more detailed information is obtained from the approved product information, a medicines information centre or some other appropriate source.

Report all suspected adverse reactions to new drugs to enable continued monitoring of their benefit–harm balance.