RARE Daily

FDA Grants Priority Review for Ipsen and Genfit’s Treatment of Rare Cholestatic Liver Disease

December 7, 2023

Rare Daily Staff

The U.S. Food and Drug Administration has accepted the New Drug Application and granted priority review for Ipsen and Genfit’s investigational elafibranor for the treatment of primary biliary cholangitis.

The FDA is expected to act on the application by June 10, 2024.

Primary biliary cholangitis (PBC) is a rare, progressive, autoimmune cholestatic liver disease in which bile ducts in the liver are gradually destroyed. The damage to bile ducts can inhibit the liver’s ability to rid the body of toxins, and can lead to scarring of liver tissue, known as cirrhosis. Common symptoms of PBC include fatigue and pruritus (itch), which can be severely debilitating. Untreated, PBC can lead to liver failure, or in some cases death. It primarily affects women, with nine women diagnosed for every man. A significant proportion of people living with PBC do not benefit from existing therapies.

Elafibranor is an oral, once-daily, dual peroxisome activated receptor (PPAR) alpha/delta (α,δ) agonist, currently under investigation as a treatment for patients with PBC. Through activation of PPAR α,δ, elafibranor targets multiple cell types and biological processes involved in the pathophysiology of PBC, including cholestasis (impairment of bile flow in the liver), bile toxicity, inflammation and fibrosis, and bile acid output. In 2019, elafibranor was granted a Breakthrough Therapy Designation by the FDA in adults with PBC who have an inadequate response to ursodeoxycholic acid (UDCA) the existing first-line therapy for PBC.

“This is a condition where many patients are living with worsening disease and debilitating symptoms despite being on treatment,” said Christelle Huguet, executive vice president and head of research and development at Ipsen. “Elafibranor, if approved, has the potential to change the management of this challenging condition for people living with PBC, offering a new second line treatment choice, where the number of effective options are currently limited.”

The European Medicines Agency has also validated Ipsen’s Marketing Authorization Application for elafibranor and the review of the submission to the EMA’s Committee for Medicinal Products for Human Use began on October 26, 2023. Furthermore, a third simultaneous regulatory filing of elafibranor has been validated for review by the U.K. Medicines and Healthcare products Regulatory Agency.

“These simultaneous regulatory submission acceptances are another important step in the elafibranor journey,” said Pascal Prigent, CEO of Genfit.

ELATIVE is a multi-center, randomized, double-blind, placebo-controlled phase 3 clinical trial, with an open-label long-term extension, which evaluated the efficacy and safety of elafibranor 80 mg once daily versus placebo for the treatment of patients with PBC with an inadequate response or intolerance to UDCA.

The trial enrolled 161 patients who were randomized 2:1 to receive either elafibranor 80mg once daily or placebo. Patients with an inadequate response to UDCA would continue to receive UDCA in combination with elafibranor or placebo, while patients unable to tolerate UDCA would receive only elafibranor or placebo. Data confirmed the potential for elafibranor to be an effective new treatment option for PBC, with 13 times more patients achieving a biochemical response, suggesting an improvement in disease progression, when treated with elafibranor compared with patients on placebo.

Photo: Pascal Prigent, CEO of Genfit

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