The European Commission has conditionally approved Ipsen's Iqirvo (elafibranor) for the treatment of primary biliary cholangitis (PBC) in adults. This marks the first new therapy for PBC to be approved in the European Union in almost a decade.
The approval extends to patients who either do not respond adequately to ursodeoxycholic acid (UDCA), the current first-line therapy, or are unable to tolerate it. Iqirvo can be used in combination with UDCA or as a monotherapy in these cases.
Clinical Trial Data
The European Commission's decision is supported by data from the Phase III ELATIVE trial (NCT04526665). The trial compared Iqirvo, administered at 80mg, plus UDCA to placebo plus UDCA. Results, published in the New England Journal of Medicine, demonstrated that patients receiving Iqirvo achieved greater treatment benefits compared to the placebo group. Specifically, 51% of patients treated with Iqirvo had their biomarkers drop to normal compared to 4% on placebo.
The ELATIVE trial's primary endpoint was the proportion of patients achieving a biochemical response, defined as alkaline phosphatase (ALP) <1.67 x upper limit of normal (ULN), an ALP decrease ≥ 15 percent, and total bilirubin ≤ ULN at 52 weeks. Top-line results showed a statistically significant treatment benefit with a 47% placebo-adjusted difference (P<0.001) between patients on Iqirvo 80mg (51%) compared with patients on placebo (4%) achieving a biochemical response.
Mechanism of Action
Iqirvo is an oral, peroxisome proliferator-activated receptor (PPAR) agonist. It functions by activating the proteins PPARα and PPARδ, which are believed to be key regulators of bile acid, inflammation, and fibrosis. By activating these receptors, Iqirvo aims to reduce bile toxicity and improve cholestasis by modulating bile acid synthesis, detoxification, and transport.
Expert Commentary
"We are delighted that Iqirvo is approved in the E.U. as an effective new option for the treatment of people living with PBC... This is despite up to half of patients being intolerant or unresponsive to current therapies," said Sandra Silvestri, Chief Medical Officer at Ipsen.
Dr. Marco Carbone, Professor of Gastroenterology at the University of Milano-Bicocca and Consultant Hepatologist at the Niguarda Liver Transplant Centre in Milan, stated, "It is a positive development in the treatment and management of PBC that we have a new, efficacious and well-tolerated treatment for our patients living with the condition... So, this new medicine, that has demonstrated its potential in managing disease progression, as well as reducing itch, a symptom that can have a detrimental effect on patients’ quality of life, is positive news for doctors and their patients."
About Primary Biliary Cholangitis
Primary biliary cholangitis is a rare, autoimmune, cholestatic liver disease affecting approximately nine women for every one man. The condition leads to a build-up of bile and toxins, causing inflammation and irreversible fibrosis of the liver and destruction of the bile ducts. If not effectively treated, PBC can worsen over time, potentially leading to liver transplant and premature death. Common symptoms include pruritus and fatigue.
Market Impact
Iqirvo's approval sets up competition with Intercept Pharmaceuticals' Ocaliva (obeticholic acid), which has been available in the European market since 2016. GlobalData’s Pharma Intelligence Centre forecasts Iqirvo to reach global sales of $361 million by 2030.
Ipsen licensed worldwide rights to the drug – apart from China, Hong Kong, Taiwan, and Macau – from Genfit for $515m in 2021. As per the agreement, Genfit will receive a $29.45m (€26.5m) milestone payment following pricing and reimbursement approval in Europe.
