Gilead's Livdelzi (Seladelpar) Receives FDA Accelerated Approval for Primary Biliary Cholangitis

Gilead Sciences, Inc. has announced the U.S. Food and Drug Administration (FDA) accelerated approval of Livdelzi® (seladelpar) for treating primary biliary cholangitis (PBC). Livdelzi can be used in combination with ursodeoxycholic acid (UDCA) for adults who do not respond adequately to UDCA, or as a monotherapy for those who cannot tolerate UDCA. However, it is not recommended for patients with decompensated cirrhosis.

This approval is based on data from the Phase 3 RESPONSE study, which showed that 62% of participants taking Livdelzi met the primary endpoint of composite biochemical response at 12 months, compared to 20% in the placebo group. Additionally, Livdelzi normalized alkaline phosphatase (ALP) levels, a key cholestatic marker predictive of liver transplant and mortality risk, in 25% of participants by month 12. None of the placebo group achieved this normalization. The study also reported a significant reduction in pruritus (chronic itching) among patients treated with Livdelzi compared to those on placebo.

Despite the promising results in ALP reduction, the improvement in survival or prevention of liver decompensation events remains undemonstrated. Therefore, continued approval of Livdelzi may depend on further verification of its clinical benefits in ongoing confirmatory trials.

Carol Roberts, President of The PBCers Organization, emphasized the importance of this new treatment, highlighting the common symptoms of PBC such as severe itching and fatigue, which significantly affect patients' quality of life. She noted that Livdelzi offers a new option that not only alleviates these symptoms but also improves crucial liver disease biomarkers.

Primary biliary cholangitis is a rare autoimmune disease affecting about 130,000 Americans, mainly women, and can lead to severe liver damage and liver failure if untreated. Livdelzi, an oral peroxisome proliferator-activated receptor (PPAR) delta agonist, represents a significant advancement in PBC treatment. It offers an effective alternative for patients who do not respond adequately to existing therapies, thereby reducing the risk of ongoing liver damage.

Daniel O’Day, Chairman and CEO of Gilead Sciences, expressed enthusiasm over the approval, noting that it provides a vital new treatment option for those living with PBC. He emphasized Gilead's commitment to leveraging their expertise in liver diseases to benefit patients.

The RESPONSE study, along with other studies including the long-term open-label ASSURE study, has provided comprehensive data on Livdelzi’s efficacy and safety. These studies collectively involve over 500 participants with PBC. Additionally, the ongoing Phase 3 AFFIRM study aims to further evaluate Livdelzi’s clinical outcomes in patients with compensated cirrhosis due to PBC.

Livdelzi remains the only treatment to show significant and sustained improvements in pruritus and cholestasis markers, crucial for assessing disease progression in PBC. The RESPONSE study's primary endpoint was a composite biochemical response at month 12, while key secondary endpoints included ALP normalization and reduction in pruritus score at month 6. The most common adverse events reported were headache, abdominal pain, nausea, abdominal distension, and dizziness, with no treatment-related serious adverse events.

Gilead has also committed to the AFFIRM study, a long-term outcomes trial, as part of the FDA’s accelerated approval conditions. This study aims to confirm the clinical benefits of Livdelzi over the long term.

Livdelzi's approval marks a significant milestone for PBC treatment, offering new hope for patients struggling with this chronic and debilitating disease. Through its innovative approach and robust clinical data, Livdelzi stands poised to make a meaningful impact on the lives of those affected by PBC.