The study is recruiting participants in the United States and three European countries who failed to respond adequately to another treatment, ursodeoxycholic acid (UDCA). Bile ducts carry bile produced in the liver to the intestines to help digest food.
“PBC is a chronic progressive liver disease characterized by immune-mediated destruction of the small intrahepatic bile ducts that if untreated progresses to end-stage liver disease and liver failure,” Dr. Velimir A. Luketic, a professor at Virginia Commonwealth University School of Medicine in Richmond, said in a press release.
“A substantial number of patients do not benefit from the currently available therapies – UDCA or OCA [beticholic acid] – either because of lack of response or intolerable side effects. This represents a major unmet need for this population,” he said.
Elafigranor targets peroxisome proliferator-activated receptors, or PPARs, which have been shown “to reduce the synthesis of bile acids and to improve detoxification of bile in the bile duct,” Luketic added. “In clinical trials, PPAR-targeting drugs have shown significant decrease in ALP, and improved biochemical profiles and pruritus in PBC patients.”
ALP stands for serum alkaline phosphate, a protein whose levels are especially high in the liver, bile ducts and bone. Doctors use levels of the protein to diagnose liver or bone disease and to see if treatments for those diseases are working.
The Phase 2 trial (NCT03124108) is a randomized, multicenter, double-blind, placebo-controlled study to assess the safety and effectiveness of elafibranor. The 45 patients will be randomized to receive one of two daily doses of elafibranor — 80 mg or 120 mg — or a placebo for 12 weeks.
The primary objective of the trial is to determine the change in elafibranor-treated patients’ ALP levels, compared with the placebo group. Secondary yardsticks of the study include the drug’s safety, whether it changes patients’ quality of life, and whether it changes their PBC risk scores.
“We are excited to have this first randomized PBC patient in this Phase 2 trial and advance our PBC program,” said Sophie Mégnien, GENFIT’s chief medical officer. “Elafibranor, a dual PPAR alpha & delta agonist, is an attractive candidate for PBC patients due to its impact on lowering alkaline phosphatase levels, as shown in previous studies, on other populations.
“This attribute, along with what PPARs have consistently demonstrated on ALP reduction, provides a strong rationale for elafibranor in PBC,” she added. “Starting randomization in such a rare disease is a key milestone, and we hope elafibranor will provide a meaningful benefit to patients, and will ultimately address the unmet need.”
Elafibranor is a pioneering drug for treating a liver disease known as non-alcoholic steatohepatitis, or NASH. It has been shown to benefit patients with moderate and advanced forms of the disease.
GENFIT is evaluating the drug in the RESOLVE-IT Phase 3 trial, which has enrolled nearly 2,000 patients at 250 centers worldwide.