Seladelpar (Livdelzi) Demonstrates Long-Term Benefit for Primary Biliary Cholangitis

Eric Lawitz, MD

Credit: Texas Liver Institute

Seladelpar (Livdelzi) provides substantial and sustained long-term benefits for patients with primary biliary cholangitis (PBC), according to new pooled interim data for up to 3 years from the phase 3 ASSURE study.¹

The findings were presented in a late-breaking abstract at The Liver Meeting 2024 from the American Association for the Study of Liver Diseases (AASLD) and showed that by month 30, seladelpar resulted in a durable and sustained composite biochemical response in 81% of patients and an alkaline phosphatase (ALP) normalization rate of 41%. Of note, no new safety signals or changes in the frequency of adverse events were observed after up to 3 years of exposure.¹

“These data support what we’ve already observed with seladelpar. The long-term data from the ASSURE study reinforce that seladelpar consistently lowers ALP, offering a promising and much-needed option for patients living with this chronic liver condition,” Eric Lawitz, MD, principal investigator and medical director of the Texas Liver Institute and a clinical professor of medicine at the University of Texas Health San Antonio, said in a press release.² “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. ALP levels are critical markers in assessing liver health, and for people with PBC who are not adequately responding to first-line therapies, reducing, or even normalizing these levels, can make a significant difference in the management of this disease.”

An ongoing, open-label study evaluating the long-term efficacy and safety of seladelpar, ASSURE enrolled adult patients with PBC who previously participated in the phase 3 RESPONSE study used to support the selective peroxisome proliferator-activated receptor delta (PPARδ) agonist’s FDA accelerated approval in August of 2024.³

The present interim analysis of ASSURE used a data cutoff of January 31, 2024, and investigated the efficacy and safety of daily seladelpar 10 mg in 337 patients with PBC, of whom 124 had ≥ 24 months of seladelpar exposure. At baseline, the mean age was 58.1 (Standard deviation, 9.7) years, most (94%) patients were female, and 16% of patients had cirrhosis.¹

The composite biochemical response endpoint was ALP <1.67 times the upper limit of normal, > a 15% reduction in ALP levels, and a normal total bilirubin level. This endpoint was met in 73% (204/280), 73% (90/124), and 81% (30/37) of patients at months 12, 24, and 30, respectively.¹

Results showed ALP normalization rates increased through month 12 and were sustained in 41% of patients through month 30. Of note, improvements in ALP levels were observed as early as month 1 and were maintained through month 30.¹

In patients with elevated alanine aminotransferase (ALT) at baseline, ALT normalized in 61% (78/127), 66% (35/53), and 90% (17/19) of patients at months 12, 24, and 30, respectively. At month 30, the mean ALT percent change from baseline was –29% among 37 patients; the mean total bilirubin percent change from baseline was –5%; and the mean gamma-glutamyl transferase percent change from baseline was –42%. Through 30 months of treatment, aspartate aminotransferase levels remained stable.¹

Of note, in the pruritus NRS, the mean change from baseline at 6 months was −3.3 among 99 patients who had moderate to severe pruritus at baseline.¹

No treatment-related serious adverse occurred in the study. Although a single fatal outcome was due to autoimmune hemolytic anemia, the investigator and sponsor deemed this event to be unrelated to seladelpar. COVID-19, pruritus, and nausea were the most common adverse events reported in the overall population of patients treated with seladelpar, and most adverse events of interest were grade 1 or 2 in severity.¹

“Gilead has a legacy of bringing groundbreaking treatments to people in need and Livdelzi is the first and only treatment to demonstrate statistically significant and durable improvements in both pruritus and markers of cholestasis related to the risk of disease progression,” said Timothy Watkins, MD, MSc, vice president of clinical development and inflammation therapeutics at Gilead.² “With Livdelzi, we’ve introduced an effective and well tolerated option for people living with PBC, offering an important novel treatment option.”

References

1. ^{Lawitz EJ, Trivedi PJ, Kowdley KV, et al. Long-Term Efficacy and Safety of Open-Label Seladelpar Treatment in Patients With Primary Biliary Cholangitis: Pooled Interim Results for up to 3 Years From the ASSURE Study. Paper presented at: AASLD’s The Liver Meeting 2024. San Diego, California. November 15-19, 2024.}
2. ^{Gilead. Gilead’s Livdelzi (Seladelpar) Demonstrated a Sustained Efficacy and Long-Term Safety Profile in Management of Primary Biliary Cholangitis. November 15, 2024. Accessed November 15, 2024. https://www.gilead.com/news/news-details/2024/gileads-livdelzi-seladelpar-demonstrated-a-sustained-efficacy-and-long-term-safety-profile-in-management-of-primary-biliary-cholangitis}
3. ^{Brooks, A. FDA Grants Accelerated Approval to Seladelpar (Livdelzi) for Primary Biliary Cholangitis. HCPLive. August 14, 2024. Accessed November 15, 2024. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-seladelpar-livdelzi-for-primary-biliary-cholangitis}