ROMA (ITALPRESS) – Gilead Sciences presented new results from a post-hoc analysis that show how seladelpar is associated with high and long-term normalization rates of an important liver marker (ALP or alkaline phosphate) in people with primitive biliary cholangitis (PBC).
In an ongoing Phase 3 study, participants with high ALP levels (between 1.0 and 1,67× ULN) showed ALP reductions after treatment. These data highlight the potential role of seladelpar in people with PBC who continue to have high levels of ALP despite the previous treatment with first-line therapy. These results are particularly relevant to people with PBC with unsuitably controlled disease based on high ALP levels – a historically subrepresented population in randomized clinical trials. The data were presented at Congress 2026 of the European Association for the Study of the Liver (EASL), held in Barcelona from 27 to 30 May.
“Achieving the standardization of the ALP is increasingly recognized as a key therapeutic target in the PBC, due to its correlation with better long-term clinical outcomes,” said Cynthia Levy, MD, Professor of Medicine and Associate Director of the Schiff Center for Liver Diseases at the University of Miami. “These data shows that seladelpar can help patients who have not achieved the normalization of the ALP to achieve this important biochemical objective and support its potential role in a wider population of people with PBC, including those with lower ALP levels.”.
The ASSURE study is a Phase 3 open-label study, currently assessing the safety and long-term effectiveness of seladelpar in people with PBC who have previously taken part in clinical trials on seladelpar. In an interim post-hoc analysis, a high and long-lasting reduction of the ALP in participants with high ALP levels at the base between 1.0 and 1.67×ULN was observed.
On 50 patients enrolled, 83% of those assessed achieved the composite normalization of the ALP – defined as ALP =1× ULN and reduction =15% – at 12 months and 74% reached the same endpoint at 24 months, demonstrating a persistent response over two years of treatment.
The average levels of ALP showed a substantial decline from the base and were kept reduced during the long-term follow-up. Improvements were also observed in other cholestasis markers, including gamma-glutamil transferase (GGT), and total bilirubin remained stable altogether. This population included individuals with risk factors related to progression of the disease, including cirrhosis and a younger age to diagnosis. Seladelpar has generally been well tolerated, without interruptions of treatment due to adverse events in the follow-up up until two years and no new security signal observed, in line with the results previously reported.
Separately, in an exploratory analysis of the entire population of the ASSURE study, 85% (n=77/91) of participants who reached the biochemical response at 12 months and were followed for 3 years has maintained or improved the measurements of liver stiffness. The stability of liver stiffness is a commonly used non-invasive marker associated with long-term results and that in this open-label analysis is of a descriptive nature.
“The data presented is added to the growing body of clinical evidence that support the role of seladelpar as a therapeutic approach in people with PBC,” said Swati Tole, MD, MS, Clinical Development, Inflammation at Gilead Sciences. “Combining the normalization of the ALP with effective symptoms management, it provides a more holistic approach to treatment. With seladelpar, we aim to intervene on both – improve itching, one of the most debilitating symptoms of the PBC, and normalize the ALP, a key marker of the risk of progression of the disease – promoting a comprehensive approach to disease management”.
Further interim analysis of the ASSURE study and the RESPONSE pivotal study help support the long-term effectiveness and safety profile of seladelpar in a wide range of people with PBC. These results are based on what has already been presented at The Liver Meeting 2025 and further support the potential of seladelpar in contributing to a lasting clinical benefit both in the population with PBC in general and in the high risk.
Seladelpar is approved for the treatment of primitive biliary cholangitis (PBC) in combination with ursodesoxylic acid (UDCA) in adults who have an inadequate response to UDCA alone, or monotherapy in those who do not tolerate UDCA, in the United States (USA), United Kingdom (UK), Australia and Israel, as well as in the European Economic Area (EEA), Switzerland and Canada. For more information about the EASL 2026 Congress and the data presented by Gilead, see the congress website.
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