Gilead Sciences' Livdelzi (seladelpar) continues to show promise in treating primary biliary cholangitis (PBC), with new data from the Phase 3 ASSURE trial demonstrating sustained efficacy and long-term safety over 2.5 years. The findings, presented at The Liver Meeting 2024, reinforce Livdelzi's potential as a valuable second-line treatment option for adults with PBC who do not respond to or cannot tolerate first-line therapies like ursodeoxycholic acid (UDCA).
Sustained Biochemical Response
The ASSURE trial (NCT03301506) tracked outcomes of continuous Livdelzi treatment in PBC patients who had previously participated in earlier trials of the drug. Results showed that 81% of patients (30 out of 37) achieved a composite biochemical response after 2.5 years. This response was defined by a decrease of at least 15% in blood alkaline phosphatase (ALP) levels to below 1.67 times the upper limit of normal, along with normalization of blood bilirubin levels. Notably, 41% of the patients achieved a complete normalization of ALP levels.
"ALP levels are recognized as an important surrogate marker of disease progression in PBC, and providers are shifting to view ALP normalization as a treatment goal," said Eric Lawitz, MD, principal investigator of ASSURE and medical director of the Texas Liver Institute. "The long-term data from the ASSURE study reinforce that [Livdelzi] consistently lowers ALP, offering a promising and much-needed option for patients living with this chronic liver condition."
Consistent Safety Profile
The safety data from the ASSURE trial remained consistent with previous findings, with no new safety concerns reported with longer-term treatment. This reinforces the favorable safety profile of Livdelzi, making it a well-tolerated option for PBC patients.
Improvements in Itching and Cholestasis
Additional data from the RESPONSE trial (NCT04620733), another Phase 3 study supporting Livdelzi's accelerated approval, further highlighted the drug's benefits. One-year results demonstrated that Livdelzi significantly reduced ALP levels compared to placebo, both in patients with compensated cirrhosis (35% vs. 6.6%) and those without cirrhosis (43.5% vs. 5.8%).
Furthermore, analyses of self-reported itching scores revealed that over a quarter (26.5%) of patients with moderate itch at baseline experienced near resolution of itch after one year of Livdelzi treatment. Near resolution was also observed in nearly a fifth (18.8%) of those initially reporting severe to very severe itch. In contrast, no such improvements were seen in the placebo group.
"Livdelzi treatment leads to statistically significant and durable improvements in both [itching] and markers of cholestasis related to the risk of disease progression," said Timothy Watkins, MD, vice president of clinical development, inflammation therapeutics at Gilead.
Long-Term Safety Database
Gilead also presented data from a large safety database of PBC patients treated with Livdelzi for up to five years. The data, encompassing 486 patients receiving the approved 10 mg dose and 152 patients on placebo, indicated that Livdelzi was generally well tolerated. Adverse event rates, serious adverse event rates, and liver-related adverse event rates were generally comparable between the two groups, with no reports of Livdelzi-related serious adverse events.
