FDA Grants Accelerated Approval to Gilead's Livdelzi for Primary Biliary Cholangitis

The recent approval of Livdelzi represents a significant advancement in the treatment of primary biliary cholangitis (PBC), particularly for patients who have not responded adequately to ursodeoxycholic acid (UDCA) or who cannot tolerate its side effects. Given the lack of a cure for PBC, Livdelzi offers a much-needed new treatment alternative for this underserved patient group.

The approval is based on positive outcomes from the pivotal Phase 3 RESPONSE study, which confirmed the medication's effectiveness and safety. In this double-blind, placebo-controlled study, 62% of patients treated with Livdelzi achieved the primary endpoint of a composite biochemical response at 12 months, compared to only 20% in the placebo group. Livdelzi also demonstrated its ability to normalize alkaline phosphatase (ALP) levels in 25% of the patients, a result not seen in any of the placebo group participants. ALP normalization is crucial as it is a key biomarker related to the risk of liver transplant and mortality. Additionally, patients reported a statistically significant reduction in pruritus, a severe chronic itching that negatively affects the quality of life for PBC sufferers.

Carol Roberts, president of The PBCers Organization, emphasized the importance of this new treatment, stating that it offers a milestone for the PBC community by potentially reducing intense itching and improving biomarkers of active liver disease.

PBC is a chronic liver disease that, if untreated, can cause severe damage and potentially lead to liver failure. Currently, there is a significant unmet need in treatment as existing options like UDCA do not work for all patients. Livdelzi, an oral peroxisome proliferator-activated receptor (PPAR) delta agonist, presents a novel approach by regulating genes involved in bile acid synthesis, inflammation, lipid metabolism, and fibrosis. Its primary aim is to reduce disease progression by normalizing ALP levels.

Daniel O’Day, chairman and chief executive officer of Gilead Sciences, acknowledged the impact of Livdelzi’s approval, highlighting that it offers an important new option for people living with PBC. He noted that Gilead, leveraging its extensive experience in liver disease, is committed to bringing this promising treatment to all who could benefit from it.

Gilead’s dedication to PBC patients extends beyond the approval of Livdelzi. The company has launched the AFFIRM study, a Phase 3 randomized, placebo-controlled trial aimed at further evaluating the long-term outcomes of Livdelzi in patients with compensated cirrhosis due to PBC. Additionally, the ASSURE study, a long-term open-label trial, along with data from earlier phase studies, enhances the understanding of Livdelzi’s sustained efficacy and safety.

Gilead also provides the Support Path Program to help patients with coverage and financial options for accessing Livdelzi. Following Gilead's acquisition of CymaBay, the company has pledged to continue supporting PBC patient organizations, underlining its long-term commitment to the PBC community.

Livdelzi has already received FDA Breakthrough Therapy and Orphan Drug Designations, and regulatory reviews are underway in the UK and EU. As part of the FDA’s accelerated approval process, continued marketing of Livdelzi depends on confirming its clinical benefits in ongoing studies, particularly its impact on reducing ALP levels.

With the approval of Livdelzi, Gilead is set to make a significant impact on the treatment landscape of PBC, offering new hope to patients with limited treatment options.