New Published Data Demonstrates Correlation Between Itch Cytokine Interleukin-31 Reduction and Pruritis Improvement in Primary Biliary Cholangitis in Phase 3 Post-Hoc Analysis of CymaBay's Seladelpar
- Statistically significant dose-dependent decreases in IL-31 were observed with seladelpar compared to placebo.
- The findings provide critical insights into the potential mediators of cholestatic itch and suggest novel therapeutic approaches for PBC patients.
- None.
Insights
The recent findings from CymaBay Therapeutics on the effect of seladelpar on IL-31 levels and associated pruritus in PBC patients represent a significant advancement in understanding the pathophysiology of cholestatic pruritus. The demonstrated correlation between IL-31 reduction and pruritus improvement offers a promising avenue for therapeutic intervention. Given the chronic nature of PBC and the impact of pruritus on patient quality of life, such targeted treatments could lead to a paradigm shift in disease management.
From a research perspective, the data provide a compelling rationale for further investigation into the role of IL-31 in PBC and other pruritic conditions. The potential of seladelpar as a first-in-class PPARδ agonist could extend beyond PBC, opening doors for its application in a range of cholestatic and inflammatory diseases where pruritus is a concern.
The positive outcomes of the Phase 3 ENHANCE study for seladelpar suggest a favorable position for CymaBay Therapeutics in the biopharmaceutical market. The specificity and efficacy of seladelpar in reducing IL-31 and bile acids, key drivers of pruritus in PBC, could differentiate it from existing treatments. This differentiation is crucial for market penetration and could lead to increased market share and revenue for CymaBay, especially in the orphan drug category where PBC treatments reside.
Investors should note the potential for seladelpar to become a cornerstone treatment for PBC, a market that has been historically underserved. The long-term financial implications hinge on the drug's approval, market acceptance and the ability of CymaBay to secure patents and regulatory exclusivity, which would protect its market position and pricing power.
The pharmacological significance of seladelpar's mechanism of action as a selective PPARδ agonist cannot be overstated. This pathway's modulation has implications not only for pruritus but also for the broader metabolic processes associated with PBC and related liver diseases. The dose-dependent response observed in the study underscores the importance of dosage optimization for achieving maximal therapeutic benefit while minimizing potential side effects.
Understanding the drug's pharmacokinetics and pharmacodynamics in relation to IL-31 and bile acid levels is essential for developing a safe and effective dosing regimen. The strong correlation between IL-31 and bile acid reductions suggests that seladelpar may exert its effects through a more systemic approach to disease management, potentially offering a more comprehensive treatment profile than current therapies.
-- First clinical trial in PBC to show coordinate reductions of IL-31, bile acids and pruritus --
In a post-hoc analysis of the Phase 3 ENHANCE study, IL-31 serum levels were measured in people with PBC who received daily oral doses of seladelpar 5 mg (n=53), 10 mg (n=53) or placebo (n=55) for three months. IL-31 is a cytokine known to mediate pruritus and blocking IL-31 signaling can provide relief in pruritic skin diseases. Statistically significant dose-dependent decreases in IL-31 were observed with seladelpar 5 mg (-
Baseline IL-31 levels also closely correlated with total (r=0.54, p<0.0001) and conjugated bile acids (up to 0.64, p<0.0001). Strong correlations were also observed between changes in IL-31 levels and changes in total bile acids (r=0.63, p<0.0001) and conjugated bile acids in the seladelpar 10 mg group.
"Pruritus is a debilitating symptom for many people living with PBC, yet the underlying mechanism of itch is not well understood," said Andreas Kremer MD, Ph.D., MHBA, Professor and Head of Hepatology, University Hospital Zurich and primary author of the study. "These latest data are critical in advancing our understanding of potential mediators of cholestatic itch and suggest that IL-31 may have a role in driving pruritis in people with PBC. While current treatments for cholestatic pruritus remain limited, these data can help inform potential novel therapeutic approaches."
About PBC
PBC is a rare, chronic inflammatory liver disease primarily affecting women (1 in 1,000 women over the age of 40 or about 130,000 total people in the US). PBC is characterized by impaired bile flow (known as cholestasis) and the accumulation of toxic bile acids in the liver, leading to inflammation and destruction of the bile ducts within the liver and causing increased levels of ALP, ALT, and GGT, enzymes found primarily in the liver, as well as total bilirubin. The most common early symptoms of PBC are pruritus (itching) and fatigue, which can be debilitating for some patients. Progression of PBC is associated with an increased risk of liver-related mortality.
About Seladelpar
Seladelpar, an investigational treatment for people with PBC, is a first-in-class oral, selective peroxisome proliferator-activated receptor delta (PPARδ) agonist, or delpar, shown to regulate critical metabolic and liver disease pathways in indications with high unmet medical need. Preclinical and clinical data support its ability to regulate genes involved in bile acid synthesis, inflammation, fibrosis and lipid metabolism, storage, and transport.
For further information, the ENHANCE Post-Hoc Analysis can be accessed here: Kremer, Andreas E.; Mayo, Marlyn J.; Hirschfield, Gideon M.; Levy, Cynthia; Bowlus, Christopher L.; Jones, David E.; Johnson, Jeff D.; McWherter, Charles A.; Choi, Yun-Jung. Seladelpar treatment reduces interleukin-31 and pruritus in patients with primary biliary cholangitis. Hepatology ():10.1097/HEP.0000000000000728, December 20, 2023. | DOI: 10.1097/HEP.0000000000000728
About CymaBay
CymaBay Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on improving the lives of people with liver and other chronic diseases that have high unmet medical need through a pipeline of innovative therapies. Our deep understanding of the underlying mechanisms of liver inflammation and fibrosis, and the unique targets that play a role in their progression, have helped us receive breakthrough therapy designation (
Cautionary Statements
Any statements made in this press release regarding the potential for seladelpar to treat PBC and potentially improve pruritus, and the future development plans of CymaBay are forward-looking statements that are subject to risks and uncertainties. Actual results and the timing of events regarding the further development of seladelpar could differ materially from those anticipated in such forward-looking statements as a result of risks and uncertainties, which include, without limitation, risks related to: the success, cost and timing of any of CymaBay's product development activities, including clinical trials; and effects observed in trials to date that may not be repeated in the future. Additional risks relating to CymaBay are contained in CymaBay's filings with the Securities and Exchange Commission, including without limitation its most recent Annual Report on Form 10-K, its Quarterly Reports on Form 10-Q and other documents subsequently filed with or furnished to the Securities and Exchange Commission. CymaBay disclaims any obligation to update these forward-looking statements except as required by law.
For additional information about CymaBay visit www.cymabay.com.
Public Relations Contact:
Theresa Dolge
Evoke Kyne
(609) 915-2156
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Investor Relations Contact:
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pkelleher@LifeSciAdvisors.com
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FAQ
What are the latest findings from CymaBay Therapeutics, Inc. (NASDAQ: CBAY) regarding PBC treatment?
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What did the study reveal about the potential mediators of cholestatic itch in people with PBC?
