FDA Grants Accelerated Approval for Rare Liver Disease Drug

The FDA has granted accelerated approval for Livdelzi (seladelpar) to treat patients with primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA). PBC is a progressive autoimmune disease that results from the destruction of the bile ducts in the liver. This leads to inflammation, scarring and cirrhosis. The disease affects mostly women.

“More people are being diagnosed with PBC, impacting people of varied ages, gender, race and ethnicity. Those living with PBC share common symptoms, including incessant itching or skin-crawling sensations, as well as debilitating fatigue that is made worse by the itching at night,” Carol Roberts, president, The PBCers Organization, said in a news release.

Livdelzi was developed by CymaBay, which was acquired by Gilead earlier this year for $4.3 billion. Livdelzi is an orally active PPARδ agonist that regulates critical metabolic and liver disease pathways. Is indicated for adults who have had an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA.

A company spokesperson said Livdelzi will be available via prescription and rolled out to pharmacies early next week across the United States. Bloomberg reports it has a monthly of $12,606 a month. The spokesperson said Gilead’s pricing decisions reflect the safety and efficacy profile demonstrating its value as an innovative new therapy option for people living with PBC as well as the costs supporting its development.

“We anticipate that most U.S. payers will cover Livdelzi, whether commercial or government health plans,” the spokesperson said. “Gilead is committed to helping patients who need our medications access them. We are advocating for broad coverage by both commercial and federal health plans for Livdelzi. Out-of-pocket costs will be determined by individual health plans; however, we do not anticipate affordability issues. For qualified patients, Gilead's patient assistance programs continue to provide Gilead medications at no charge and provide other offerings to facilitate access.”

Related: Accelerated FDA Approval Granted for Treatment of Rare Autoimmune Liver Disease

This is the second new therapy for PBC approved by the FDA this summer. In June 2024, the FDA granted accelerated approval to Ipsen’s Iqirvo (elafibranor), which has a list price of $11,500 for a month’s supply, according to Reuters.

The approval of Livdelzi was based on the phase 3 RESPONSE study, in which 62% of patients taking Livdeliz achieved the primary endpoint of composite biochemical response at month 12, versus 20% of participants taking placebo.

Treatment with Livdelzi led to normalization of alkaline phosphatase (ALP) values, which is a predictor of risk for liver transplant and death, in 25% of trial participants at month 12. This change was not seen in any trial participants receiving placebo. Change from baseline itch score at month 6 was a key secondary endpoint; patients treated with Livdelzi demonstrated a statistically significant reduction in itch compared with placebo.

The label for Livdelzi includes warnings about the risk of fractures. About 4% of patients treated with Livdelzi experienced fracture compared with no placebo-treated patients. Additionally, treatment with Livdelizi has been associated with dose-related increases in serum transaminase level, and the label recommends monitoring liver enzyme levels during treatment and discontinue if tests worsen or if patient develops hepatitis.

In the clinical trials, the most common adverse events were headache, abdominal pain, nausea, abdominal distention and dizziness.

Gilead indicates that a confirmatory trial called AFFIRM has already been initiated in people with compensated cirrhosis.