Ipsen, Genfit Tout Phase III Data for Liver Disease Drug, Seek FDA and EMA Approvals

Physician shows shape of liver

Pictured: Physician shows shape of liver/iStock, Shidlovski

With positive Phase III topline data in hand for a rare liver disease, Ipsen and Genfit announced Friday preparations to submit elafibranor to the FDA and European Medicines Agency for regulatory approvals. 

In the pivotal Phase III ELATIVE trial, elafibranor went up against the placebo for primary biliary cholangitis (PBC) patients who do not respond well or cannot take ursodeoxycholic acid (UDCA), the standard treatment. In the drug arm, 51% of patients achieved a cholestasis response compared to 4% on placebo.  

An improvement was also seen in patients’ Worst Itching Intensity Numerical Rating Scale score compared to placebo. Pruritus is a common and frustrating side effect for patients with PBC. The severe itching can lead to sleep disturbances, fatigue and depression.  

PBC is a rare, autoimmune cholestatic liver disease affecting primarily middle-aged women, approximately 65 out of every 100,000. The progressive disease results in a slow destruction of the small bile ducts of the liver, causing bile and toxin buildup. UDCA is the common first-line treatment, but many patients don’t respond. 

In 2019, elafibranor was granted a Breakthrough Therapy designation by the FDA in adults with PBC who have an inadequate response to UDCA. 

Now, Ipsen is ready to seek the FDA’s approval for elafibranor as a second-line treatment for PBC for potential approval.  

The double peroxisome proliferator-activated receptor α/δ agonist was originally in development by Genfit for the treatment of non-alcoholic steatohepatitis (NASH). Following negative interim data, the program was scrapped in 2020 as part of corporate strategy. The following year, Ipsen dropped $130 million upfront for global rights to develop and commercialize elafibranor for PBC, with another $392 million on the line in milestone payments as well as royalties of up to 20%. 

Elafibranor will give Intercept Pharmaceuticals a run for its money. Intercept’s Ocaliva was approved in 2016 for PBC, then restricted by the FDA in 2021 for patients with advanced cirrhosis due to risk of serious liver injury.  

It’s the only approved second-line treatment for PBC patients, but Ipsen’s latest data is creating a showdown with Intercept. Using the same endpoint as the trial for elafibranor, 46% on Intercept’s Ocaliva met the primary endpoint versus 10% of the placebo group. Additionally, Ocaliva appears to exacerbate instead of alleviate pruritus symptoms for some, and is listed as one of the drug’s adverse reactions. 

Ocaliva had also been in the running as a potential treatment for NASH disease, but last week the FDA again denied Intercept’s application to approve it for the indication. Intercept announced it is abandoning its NASH program. The company is laying off about a third of its workforce. 

Ipsen has kept the FDA busy this summer. Earlier this month, Bylvay (odevixibat), Ipsen’s ileal bile acid transporter inhibitor, earned a second rare cholestatic liver disease indication for patients with pruritus due to Alagille syndrome. And on Wednesday, an FDA advisory committee voted 10-4 in support of the safety and efficacy of Ipsen’s palovarotene, a medication to treat an ultra-rare disease that causes fibrous connective tissue to turn into bone tissue. The committee voted 11-3 that the benefits of the drug outweighed the risk.  

Kate Goodwin is a freelance life science writer based in Des Moines, Iowa. She can be reached at kate.goodwin@biospace.com and on LinkedIn.   

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