Andreas Kremer, MD, PhD, MHBA, is the head of hepatology at University Hospital Zurich in Switzerland.

Andreas Kremer, MD, PhD, MHBA

Seladelpar’s Impact on Pruritus

 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)

Along with a late-breaking presentation highlighting seladelpar’s sustained efficacy and long-term safety in a 2.5-year interim analysis of the ongoing open-label phase 3 ASSURE study, another abstract presentation focused on the agent’s impact on pruritus in the RESPONSE trial.

In this segment, which is the final installment of a 4-part series, Andreas Kremer, MD, PhD, MHBA, head of hepatology at University Hospital Zurich, explains seladelpar’s impact on pruritus symptoms in patients with PBC.

Kremer delves into the promising outcomes of recent studies on seladelpar and its potential to alleviate pruritus in PBC, specifically focusing on a posthoc analysis revealing that patients with moderate to severe pruritus who were treated with seladelpar achieved a significant reduction on the numeric rating scale (NRS) for symptom severity.

In addition to improvements in pruritus among patients who reported itch at baseline, Kremer pointed out patients who reported no pruritus at baseline who were treated with seladelpar did not report any new-onset pruritus, whereas 25% of those on placebo developed pruritus during the same period. In totality, the findings underscore the potential antipruritic efficacy of seladelpar alongside its primary anti-cholestatic and anti-inflammatory properties.

Kremer points to an exciting future for PBC management, with new therapies on the horizon poised to improve both disease outcomes and quality of life for patients.

Editors’ note: Kremer has relevant disclosures with AbbVie, AstraZeneca, Bayer, CymaBay, Gilead, GlaxoSmithKline, Intercept, Mirum, Takeda, Ipsen, and others.

Brooks A. FDA Grants Accelerated Approval to Seladelpar (Livdelzi) for Primary Biliary Cholangitis. 

. August 14, 2024. Accessed December 6, 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. 

. November 15, 2024. Accessed December 6, 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, notably seladelpar, a PPAR delta agonist. Recent studies, including the ASSURE and RESPONSE trials, highlight seladelpar's sustained efficacy, long-term safety, and significant impact on pruritus symptoms in PBC patients. Notably, seladelpar reduced pruritus severity in patients with moderate to severe symptoms and prevented new-onset pruritus in those without baseline symptoms. These findings suggest seladelpar's potential to enhance disease management and patient quality of life.

Andreas Kremer, MD, PhD, MHBA, explains seladelpar’s impact on pruritus in PBC based on findings from a posthoc analysis of the RESPONSE trial.

Emerging Second-Line Therapies in PBC

In this segment, which is part 3 of a 4-part series, Andreas Kremer, MD, PhD, MHBA, head of hepatology at University Hospital Zurich, reviews emerging second-line therapies in PBC.

Kremer provides an overview of promising advancements in the treatment of pruritus in PBC, focusing on 2 recently FDA-approved PPAR agonist therapies: elafibranor and seladelpar. He explains how these drugs target PPAR to address the underlying mechanisms of PBC. Both seladelpar, a specific PPAR delta agonist, and elafibranor, a dual PPAR alpha and delta agonist, exhibit anticholestatic and anti-inflammatory properties, making them effective options for treating the disease's root causes.

Highlighting recent clinical advancements, Kremer highlights seladelpar's performance in a phase 3 trial where the drug met its pre-specified secondary endpoint for significantly reducing pruritus severity, as measured by the numeric rating scale. He additionally called attention to a posthoc analysis from the study that revealed a strong anti-pruritic effect in certain patient subgroups, offering additional hope for tailored treatment approaches.

The treatment landscape for primary biliary cholangitis (PBC) has evolved significantly with the introduction of two new second-line therapies in 2024, including seladelpar, a PPAR delta agonist. Seladelpar's efficacy and safety were highlighted at The Liver Meeting 2024, with studies showing its impact on pruritus and long-term benefits. Andreas Kremer, MD, PhD, discussed the advancements in PBC treatment, focusing on seladelpar and elafibranor, both PPAR agonists with anticholestatic and anti-inflammatory properties. Seladelpar's phase 3 trial results showed significant pruritus reduction, offering hope for personalized treatment strategies.

Andreas Kremer, MD, PhD, MHBA, reviews emerging therapies in PBC, focusing specifically on seladelpar and its impact on pruritus.

Unmet Needs for Pruritus Management in PBC

In this segment, which is part 2 of a 4-part series, Andreas Kremer, MD, PhD, MHBA, head of hepatology at University Hospital Zurich, explains current unmet needs for pruritus care in PBC management.

Kremer calls attention to a critical gap in managing pruritus in patients with PBC, highlighting the unmet need for therapies that address both the underlying disease and symptom burden. He notes that current in-label treatments, such as ursodeoxycholic acid and obeticholic acid, have not demonstrated efficacy in alleviating pruritus, and in some cases, these therapies may even exacerbate the symptom despite their proven ability to reduce cholestasis.

Kremer stresses the importance of developing new, in-label drugs that are not only effective but also safe and well-tolerated for long-term use. He expresses optimism about ongoing advancements, noting promising developments in the pharmaceutical pipeline targeting rare liver diseases that offer hope for more comprehensive treatment strategies that address both the clinical and symptom-related aspects of PBC.

The treatment landscape for primary biliary cholangitis (PBC) has evolved with the introduction of new second-line therapies, including seladelpar, a PPAR delta agonist. Recent studies presented at The Liver Meeting 2024 highlighted seladelpar's sustained efficacy and safety, as well as its impact on pruritus. Current treatments like ursodeoxycholic acid and obeticholic acid have limited efficacy in managing pruritus, underscoring the need for new therapies. Ongoing advancements in the pharmaceutical pipeline offer hope for more comprehensive treatment strategies addressing both clinical and symptom-related aspects of PBC.

Andreas Kremer, MD, PhD, MHBA, explains shortcomings of traditional PBC therapies for addressing pruritus and what advantages newer agents may offer.

Understanding Pruritus in Primary Biliary Cholangitis

In this segment, which is part 1 of a 4-part series, Andreas Kremer, MD, PhD, MHBA, head of hepatology at University Hospital Zurich, explains the burden of pruritus in PBC and its negative impact on affected patients’ quality of life.

Kremer highlights the widespread prevalence of pruritus in PBC, affecting anywhere between 30% and 80% of patients depending on the source. Beyond its severity measured on the numeric rating scale, Kremer describes how pruritus profoundly impacts quality of life, disrupts sleep, induces fatigue and depression, and impairs daily functioning and work capacity.

He goes on to describe the psychological challenges it poses, particularly in social and professional settings, where visible discomfort can exacerbate emotional strain. Ultimately, the multifaceted toll pruritus takes on patients underscores the critical need for effective management strategies.

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 studies showing its impact on pruritus, a common and debilitating symptom of PBC. Pruritus affects 30-80% of PBC patients, significantly impairing quality of life, sleep, and daily functioning. The psychological and social challenges it poses emphasize the need for effective management strategies to alleviate this burden on patients.

Andreas Kremer, MD, PhD, MHBA, describes the burden of pruritus in PBC and the toll it can take on patients’ quality of life.

Andreas Kremer, MD, PhD, MHBA

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