Primary biliary cholangitis: encouraging results from experimental therapy

It is a rare cholestatic liver disease that is making headlines today thanks to positive results from the Phase 3 Elative study evaluating the efficacy and safety of elafibranor, an investigational PPAR α,δ dual agonist, for the treatment of patients with a rare cholestatic liver disease, primary biliary cholangitis (PBC), who develop an inadequate response or intolerance to the current standard of care ursodeoxycholic acid (UDCA).

Good results for 51% of patients

In the study, the results of which were announced by Ipsen and Genfit, 51% of patients treated with elafibranor 80mg achieved a response in terms of improvement in parameters related to cholestasis compared to 4% of those treated with placebo. Response is defined in the study as alkaline phosphatase (ALP) <1.67 relative to upper limit of normal (ULN), ALP decrease ≥15%, and total bilirubin (TB) ≤ULN at 52 weeks. ALP and bilirubin are important predictors of disease progression. Reduction in the levels of both may indicate a reduction in cholestatic damage and an improvement in liver function. “These encouraging results indicate that elafibranor could be an effective treatment to prevent progression of primary biliary cholangitis in patients treated with ursodeoxycholic acid. The drug has a good safety profile, was well tolerated and could prove to be an important new treatment option for the long-term treatment of patients with this debilitating disease,” he says. Howard MayerExecutive Vice President, Head of Research and Development at Ipsen.

Normalization of alkaline phosphatase

The first secondary endpoint, normalization of alkaline phosphatase (ALP) at week 52, also had statistically significant improvements with elafibranor versus placebo. For pruritus, another secondary endpoint, a trend towards symptom improvement with a greater reduction from baseline in the PBC Worst Itch NRS score was observed in patients treated with elafibranor compared to those treated with placebo, but there was no reached statistical significance. In the study, elafibranor was generally well tolerated with a safety profile consistent with that observed in previously reported studies. “We are pleased with these results because primary biliary cholangitis remains a disease with significant unmet treatment needs,” he adds. Pascal Prigent, Chief Executive Officer of GENFIT. “This long-awaited result is good news for patients and healthcare professionals who need more options to improve the clinical management of patients with PBC. It is also a gratifying recognition of the quality of our team’s work and of GENFIT’s ability to innovate and deliver tangible results”.

What is primary biliary cholangitis

Primary biliary cholangitis is a rare, progressive, autoimmune cholestatic liver disease characterized by the gradual destruction of the small hepatic bile ducts. Damage to the bile ducts can inhibit the liver’s ability to rid the body of toxins and cause fibrous scarring of the liver tissue, known as cirrhosis. The most common symptoms of PBC include fatigue and itching, which can become severely debilitating. Left untreated, PBC can lead to liver failure, and in some cases, death. It is also the main cause of liver transplantation. It particularly affects middle-aged women; out of ten diagnoses, nine affect women. It is a disease in which a large percentage of patients do not benefit from current therapies. The prevalence of people living with PBC is estimated to be between 23.9 and 39.2 per 100,000 in the United States and 22.27 per 100,000 in Europe.