Seladelpar lysine dihydrate

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.

Ipsen on Monday secured an accelerated approval from the FDA for Iqirvo (elafibranor), making the oral PPAR agonist the first new medicine cleared in the US for primary biliary cholangitis (PBC) in nearly a decade.The filing, which was granted priority review, was based on positive data from the Phase III ELATIVE trial, published in the NEJM. The study demonstrated a 47% benefit with Iqirvo plus ursodeoxycholic acid (UDCA) on the composite primary endpoint, compared to placebo plus UDCA. Its main goal of cholestasis response was defined as alkaline phosphatase (ALP) <1.67 times the upper limit of normal (ULN), an ALP decrease ≥15% and total bilirubin ≤ULN at one year."For a significant number of people living with PBC, available treatments do not control the condition and may exacerbate symptoms of PBC. Left unmanaged, PBC can progress, leading to liver failure and in some cases, the need for a liver transplant… Iqirvo is therefore a much-needed treatment option," said Christelle Huguet, head of R&D at Ipsen.The US label for Iqirvo calls for it to be given together with UDCA in adults who have an inadequate response to UDCA, or as monotherapy if they cannot tolerate UDCA. In 2021 Ipsen in-licensed the drug from Genfit, who now expects to receive €89 million ($95.8 million) in milestone payments this year.Ipsen is not the only player in the race for effective PBC therapies. Seladelpar, a PPAR delta agonist recently acquired by Gilead Sciences as part of its $4.3-billion takeout of CymaBay Therapeutics, is also under review at the FDA with an action date of August 14. Last week, Gilead shared additional long-term data on the drug, including steady improvement on the composite endpoint, as well as itch relief.Key opinion leader (KOL) James Boyer recently weighed in on where PPAR agonists could fit into the treatment paradigm. In an interview with FirstWord, he suggested that patients needing alternative therapy after UDCA are typically put on Intercept Pharmaceuticals' Ocaliva (obeticholic acid), but those with elevated ALP levels or itching may switch to Iqirvo or seladelpar. Patients with elevated ALP after at least six months on UDCA will likely be treated with PPAR agonists instead of Ocaliva moving forward, he added.For more on that interview, see – KOL Views Q&A: Leading expert sizes up PPAR battle between elafibranor, seladelpar in PBC.