Palak Trivedi, MD, PhD

Trivedi and Lawitz review long-term data from the phase 3 open-label ASSURE study and explain what they add to our understanding of seladelpar for PBC.

Insights from Long-Term ASSURE Data for Seladelpar

 treatment landscape has long been limited to just a handful of agents with limited efficacy, 2024 saw a major shift in PBC management with the addition of 2 new second-line therapies.

Seladelpar (Livdelzi), a proliferator-activated receptor (PPAR) delta agonist, was one of these recent additions to the PBC treatment armamentarium and was a major topic of discussion at 

The Liver Meeting 2024 from the American Association for the Study of Liver Diseases (AASLD)

Findings from a 2.5-year interim analysis of the ongoing open-label phase 3 ASSURE study were presented in a late-breaking abstract at the meeting and highlight seladelpar’s sustained efficacy and long-term safety for the treatment of PBC.

In this segment, which is the final installment of a 4-part series, experts Palak Trivedi, MD, PhD, and Eric Lawitz, MD, discuss the long-term ASSURE data and what they add to our understanding of seladelpar’s safety and efficacy for PBC.

Trivedi begins by emphasizing the significance of seladelpar’s long-term safety profile, calling attention to the lack of new treatment-emergent adverse events or concerning safety signals. While acknowledging the inherent limitations of safety extension studies without matched control groups, he describes how the ASSURE data provide confidence in the drug’s sustained biochemical response and tolerability, additionally advocating for real-world studies to validate these findings and establish whether seladelpar improves transplant-free survival over time beyond its biochemical markers.

Similar to Trivedi, Lawitz highlights the importance of long-term follow-up in chronic therapies. He notes that the ASSURE data not only confirm the stability of seladelpar’s safety profile but also reveal a potential increase in efficacy with extended treatment. He notes the consistent durability and lack of unexpected toxicities offer clinicians greater confidence in prescribing seladelpar for prolonged use.

: associate professor and honorary consultant hepatologist and clinical research director for industry engagement at the University of Birmingham

: medical director of the Texas Liver Institute and a clinical professor of medicine at the University of Texas Health San Antonio

Relevant disclosures for Trivedi include Bristol Myers Squibb, Gilead, Intercept, CymbaBay, and others. Relevant disclosures for Lawitz include 89Bio, Boehringer Ingelheim, Merck, Novo Nordisk, Sagimet Biosciences, AstraZeneca, Bristol Myers-Squibb, Cymabay, Eli Lilly, Gilead Sciences, GlaxoSmithKline, Intercept, Ipsen, Madrigal, Novartis, Regeneron, Takeda, Terns, Viking Therapeutics, AbbVie, and others.

Brooks A. FDA Grants Accelerated Approval to Seladelpar (Livdelzi) for Primary Biliary Cholangitis. HCPLive. August 14, 2024. Accessed December 4, 2024. 

https://www.hcplive.com/view/fda-grants-accelerated-approval-to-seladelpar-livdelzi-for-primary-biliary-cholangitis

Brooks A. Seladelpar (Livdelzi) Demonstrates Long-Term Benefit for Primary Biliary Cholangitis. HCpLive. November 15, 2024. Accessed December 4, 2024. 

https://www.hcplive.com/view/seladelpar-livdelzi-demonstrates-long-term-benefit-primary-biliary-cholangitis

Videos

The treatment landscape for primary biliary cholangitis (PBC) has evolved with the introduction of new second-line therapies, including seladelpar, a PPAR delta agonist. At The Liver Meeting 2024, findings from the ASSURE study highlighted seladelpar's sustained efficacy and long-term safety. Experts Palak Trivedi and Eric Lawitz emphasized the drug's stable safety profile and potential increased efficacy over time. They advocated for real-world studies to further validate these findings and assess seladelpar's impact on transplant-free survival beyond biochemical markers.

Trivedi and Lawitz discuss what sets seladelpar apart from other PBC therapies in the rapidly evolving treatment landscape.

What Sets Seladelpar Apart From Other PBC Therapies

In this segment, which is part 3 of a 4-part series, experts Palak Trivedi, MD, PhD, and Eric Lawitz, MD, discuss what sets seladelpar apart in the evolving landscape of PBC therapies.

Trivedi emphasizes seladelpar’s unique design as a PPAR delta agonist, citing clinical trial data that demonstrated its significant impact on both liver biochemistry and patient symptoms, particularly pruritus. He notes the importance of this data in guiding treatment choices, especially in the absence of head-to-head comparisons with other recently introduced agents and as clinicians start to face critical questions on sequencing and tailoring therapies to individual patient needs.

Lawitz adds that seladelpar’s combination of efficacy and tolerability distinguishes it from other second-line treatments. He says its unique ability to alleviate pruritus, a symptom notoriously difficult to manage in this patient population, not only enhances quality of life but also addresses a key gap in patient-centered care.

The treatment landscape for primary biliary cholangitis (PBC) has evolved with the introduction of new second-line therapies, including seladelpar, a PPAR delta agonist. Seladelpar's sustained efficacy and long-term safety were highlighted in a 2.5-year interim analysis of the ASSURE study. Experts emphasize its unique design and ability to significantly impact liver biochemistry and alleviate pruritus, a challenging symptom in PBC patients. This advancement addresses a critical gap in patient-centered care, offering improved quality of life and guiding treatment choices in the absence of direct comparisons with other agents.

Trivedi and Lawitz discuss the clinical impact of having seladelpar as a second-line treatment option for patients with PBC.

The Clinical Impact of Seladelpar in PBC Care

In this segment, which is part 2 of a 4-part series, experts Palak Trivedi, MD, PhD, and Eric Lawitz, MD, discuss the clinical impact of having seladelpar as a treatment option for patients with PBC.

Trivedi begins by highlighting the various benefits of seladelpar, which addresses both clinical outcomes—such as improved liver blood tests and enhanced transplant-free survival—and patient-centered concerns like pruritus, which significantly affects quality of life.

Lawitz goes on to emphasize the importance of seladelpar for patients who either do not adequately respond to or cannot tolerate UDCA. For this underserved group, he says seladelpar provides a much-needed option to improve liver function and potentially prevent disease progression.

Brooks A. Seladelpar (Livdelzi) Demonstrates Long-Term Benefit for Primary Biliary Cholangitis. HCPLive. November 15, 2024. Accessed December 4, 2024. 

The treatment landscape for primary biliary cholangitis (PBC) has evolved significantly with the introduction of two new second-line therapies in 2024, including seladelpar (Livdelzi), a PPAR delta agonist. Seladelpar's sustained efficacy and long-term safety were highlighted in a 2.5-year interim analysis of the phase 3 ASSURE study, presented at The Liver Meeting 2024. Experts emphasize seladelpar's benefits in improving liver function, enhancing transplant-free survival, and addressing pruritus, particularly for patients unresponsive to or intolerant of UDCA, offering a crucial alternative for this underserved group.

Trivedi and Lawitz discuss seladelpar’s mechanism of action and its use as a second-line therapy in PBC.

Understanding Seladelpar as a Second-Line Treatment for PBC

In this segment, which is part 1 of a 4-part series, experts Palak Trivedi, MD, PhD, and Eric Lawitz, MD, discuss seladelpar and its emerging role as a second-line therapy for PBC.

Trivedi begins by explaining that seladelpar offers a more targeted mechanism of action compared with traditional therapies, optimizing bile transport within the liver with a focused approach that not only improves and normalizes liver blood tests in a substantial proportion of patients, but also correlates with better long-term, transplant-free survival. He highlights its impact on quality of life, with long-term data showing significant relief of pruritus—a symptom commonly reported by patients with PBC.

Lawitz goes on to emphasize seladelpar’s efficacy in patients unable to tolerate or inadequately responsive to UDCA. By improving alkaline phosphatase levels and, in some cases, achieving normalization, he asserts that seladelpar holds promise in mitigating disease progression.

The treatment landscape for primary biliary cholangitis (PBC) has evolved with the introduction of new second-line therapies, including seladelpar, a PPAR delta agonist. Seladelpar's efficacy and safety were highlighted at The Liver Meeting 2024, with findings from the ASSURE study showing its potential in improving liver function and quality of life. Experts Palak Trivedi and Eric Lawitz discussed its targeted mechanism, which optimizes bile transport and offers benefits for patients unresponsive to UDCA. Seladelpar's role in mitigating disease progression and improving pruritus symptoms was emphasized.

Palak Trivedi, MD, PhD

Articles