FDA Approves Ipsen's Iqirvo as First PPAR Agonist for Primary Biliary Cholangitis

Ipsen has achieved accelerated FDA approval for Iqirvo (elafibranor), marking it as the first new oral PPAR agonist treatment for primary biliary cholangitis (PBC) to be introduced in the United States in nearly ten years. The FDA's priority review of the drug was based on promising outcomes from the Phase III ELATIVE trial, which were published in the New England Journal of Medicine (NEJM). The trial revealed that Iqirvo combined with ursodeoxycholic acid (UDCA) provided a 47% improvement on the composite primary endpoint when compared to a placebo plus UDCA. The primary endpoint was a cholestasis response, defined by an alkaline phosphatase (ALP) level below 1.67 times the upper limit of normal (ULN), a reduction in ALP by at least 15%, and total bilirubin levels within the ULN over one year.

Christelle Huguet, head of R&D at Ipsen, emphasized the importance of Iqirvo for PBC patients whose current treatments do not adequately manage the condition, potentially leading to liver failure or the need for a liver transplant. Huguet highlighted that Iqirvo offers a critical new treatment option for these patients.

The FDA's approved labeling for Iqirvo mandates its use in combination with UDCA for adults who have not responded adequately to UDCA alone, or as a monotherapy for those who cannot tolerate UDCA. Ipsen secured the rights to Iqirvo from Genfit in 2021, with Genfit anticipating milestone payments totaling €89 million ($95.8 million) within the year.

The landscape for PBC therapies is competitive, with other contenders like Gilead Sciences' seladelpar, a PPAR delta agonist acquired through Gilead's $4.3-billion purchase of CymaBay Therapeutics. Seladelpar is also under FDA review, with an action date set for August 14. Gilead recently shared encouraging long-term data on seladelpar, highlighting continuous improvement on the composite endpoint and relief from itching.

James Boyer, a key opinion leader in the field, recently discussed the potential role of PPAR agonists in PBC treatment during an interview with FirstWord. Boyer explained that patients requiring alternative therapies after UDCA typically receive Intercept Pharmaceuticals' Ocaliva (obeticholic acid). However, patients with elevated ALP levels or itching issues may switch to Iqirvo or seladelpar. According to Boyer, those with persistently high ALP levels after at least six months on UDCA will probably be treated with PPAR agonists instead of Ocaliva in the future.

In summary, Ipsen's Iqirvo brings a new hope for PBC patients, offering an alternative for those not adequately managed by existing treatments. The drug's approval signifies a major advancement in the treatment landscape for this liver condition. Meanwhile, the competition remains strong with other emerging therapies like Gilead's seladelpar, which also shows promising results in improving patient outcomes.