Seladelpar lysine dihydrate

Ipsen's elafibranor, branded Iqirvo, has received accelerated approval from the FDA for treating primary biliary cholangitis (PBC) in adults, marking the first new treatment for PBC in nearly a decade. The approval is based on positive results from the phase 3 ELATIVE trial, showing significant improvements in biochemical response compared to existing treatments. In the trial, 70% of patients on elafibranor showed biochemical improvement, compared to none on placebo. The improvement was measured by lower alkaline phosphatase levels and total bilirubin. Iqirvo also helped improve itch-related quality of life. PBC, a rare autoimmune liver disease affecting around 100,000 people in the U.S., can lead to liver failure if untreated. Iqirvo, approved for use in combination with ursodeoxycholic acid (UDCA) or as monotherapy, offers a new option for patients who do not respond adequately to UDCA or cannot tolerate it. Iqirvo is a first-in-class medication designed as an oral, once-daily peroxisome proliferator-activated receptor (PPAR) agonist. By activating PPAR receptors, Iqirvo helps to regulate gene expression involved in lipid metabolism and inflammation, offering a novel mechanism of action that sets it apart from existing treatments. The drug is also under review by the EMA and the UK Medicines and Healthcare products Regulatory Agency, with decisions expected later this year. Gilead is also chasing a PBC approval. Seladelpar, picked up in its recent $4.3 billion acquisition of CymaBay Therapeutics, is an oral PPAR-delta agonist targeting liver disease pathways. In its phase 3 trial , 70% of patients responded positively to seladelpar, with 37% achieving normal biomarker levels. The treatment is under priority review by the FDA with an anticipated decision in August.

Three years after Ispen licensed elafibranor from Genfit, it has gained FDA approval to treat the rare liver disorder primary biliary cholangitis (PBC). Once hyped as a potential blockbuster medicine for metabolic-associated steatohepatitis (MASH), Ipsen and Genfit’s elafibranor has found its calling as a treatment for a lower-profile liver disorder. The FDA has approved Iqirvo for primary biliary cholangitis (PBC), a chronic autoimmune condition which affects approximately 100,000 people in the U.S., most of them women between the ages of 30 and 60. PBC causes a buildup of bile and toxins, leading to inflammation and fibrosis of the liver. Over time, patients become increasingly fatigued and develop a debilitating itch (pruritis). In the absence of treatment, the condition can require a liver transplant or lead to premature death. Ipsen will charge $11,500 for a month’s supply of the first-in-class peroxisome proliferator-activated receptor (PPAR) agonist. After weak data eliminated elafibranor as a potential candidate for MASH, Ipsen in-licensed it from Genfit in 2021 as a treatment for PBC for 480 million euros ($515 million). The FDA endorsement is an accelerated nod, based on data showing that an 80 mg tablet of elafibranor reduces the rate of production of the alkaline phosphatase (ALP) enzyme—a key biomarker indicating the extent of liver damage. Achievement of a full approval will depend on success in confirmatory trials determining whether Iqirvo can improve survival and prevent abdominal swelling or gastrointestinal bleeding. The approval sets the two French companies up to compete with Intercept Pharmaceuticals’ Ocaliva, which has been on the market for eight years. Before Intercept was acquired by Italian private company Alfasigma last year, it expected sales of Ocaliva in 2023 to reach between $320 million and $340 million. Analysts estimate (PDF) sales of Iqirvo to reach 193 million euros ($207 million) in 2027. Peak sales have been tabbed at 400 million euros ($429 million). Alfasigma made its buyout of New Jersey-based Intercept shortly after the FDA rejected a bid for approval of Ocaliva in MASH for the second time in three years. Both Iqirvo and Ocaliva are approved for PBC in combination with ursodecxycholic acid (UDCA) or as a monotherapy in patients that can not take UDCA. Analysts at ODDO BHF said that the approval for Ipsen “marks a success story in the active business development policy since the appointment of current CEO David Loew in 2020,” and raises hopes for other partnerships. In regard to Iqirvo, however, one warning ODDO BHF had for investors is the lack of a reduction in pruritis on the label. The characteristic has “been seen as a weakness of Iqirvo,” the analysts wrote, especially in comparison to another drug expected to be approved in the indication in August—CymaBay Therapeutics’ seladelpar. In February of this year, Gilead gained the asset with a $4.3 billion buyout of CymaBay.