Livdelzi Approved for Primary Biliary Cholangitis

On August 14, 2024, the U.S. Food and Drug Administration (FDA) approved Gilead Sciences’ Livdelzi^® (seladelpar). It’s a peroxisome proliferator-activated receptor (PPAR)-delta agonist for treating adults with primary biliary cholangitis (PBC). It should be used in combination with ursodeoxycholic acid (UDCA) for those patients who do not fully respond to UDCA. It can also be used as monotherapy for patients who cannot tolerate UDCA. Its recommended dose is 10mg orally once per day. Gilead plans to launch Livdelzi starting early next week at a wholesale acquisition cost (WAC) of about $12,606 for a month’s supply. Full prescribing information can be found here.

At a Glance

• Brand Drug: Livdelzi (seladelpar)
• Manufacturer: Gilead Sciences
• Date Approved: August 14, 2024
• Indication: for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA
• Dosage Forms Available: 10mg oral capsules
• Launch Date: Early next week
• Estimated Annual Cost: approximately $151,272 per year
• PBC is an inflammatory autoimmune condition that destroys bile ducts. As a result, bile gradually accumulates in the liver, eventually causing irreversible liver damage. PBC is a major cause of liver transplants.
• PBC affects about 130,000 U.S. patients, but its onset is gradual, so most patients typically are not diagnosed with it until after the age of 30. Between 75% and 90% of patients are women.
• While its mechanism is not fully understood, Livdelzi is believed to work by inhibiting bile acid synthesis by activating PPAR-delta receptors.
• Accelerated approval was granted based on the results of the Phase III RESPONSE trial. In this trial, a higher percentage of patients receiving Livdelzi had a biochemical response – including reduced levels of alkaline phosphatase (ALP), a surrogate marker of response – compared to those receiving placebo (62% versus 20%, respectively). Livdelzi was also effective in reducing pruritis (itch) in these patients, which is a common symptom of PBC.
• The most frequent adverse events in the trial were headache, abdominal pain, nausea, abdominal distension (swelling), and dizziness.
• Ocaliva^® (obeticholic acid – Intercept), a farnesoid X receptor (FXR) agonist, is also indicated for the treatment of PBC in patients whose response to UDCA is considered inadequate (as an add-on to UDCA) and as a monotherapy for patients unable to tolerate UDCA.
• Ipsen’s Iqirvo^® (elafibranor) is an oral PPAR agonist that was approved for a similar PBC indication on June 10, 2024.
• Livdelzi received Accelerated Approval, so continued approval for this indication is contingent upon the demonstration of clinical benefit in confirmatory trials. It also is designated as a Breakthrough Therapy and has Orphan Drug status.