Investigational Seladelpar Demonstrates Significant Improvements in Liver Disease Progression and Reduced Itching in Primary Biliary Cholangitis
Gilead Sciences (GILD) has announced interim results from the ASSURE study, which show that seladelpar, an investigational PPAR delta agonist, significantly improves liver disease markers and reduces itching in primary biliary cholangitis (PBC) patients. The study enrolled 174 patients, with 70% of those treated for 12 months meeting the composite endpoint, and 37% achieving ALP normalization. Seladelpar also reduced other liver injury markers. No serious adverse events were reported. This data aligns with the Phase 3 RESPONSE study, highlighting seladelpar's potential as a new therapy for PBC. The FDA has accepted a New Drug Application for seladelpar, with a decision expected in August 2024.
- 70% of patients on seladelpar achieved the composite endpoint at 12 months.
- 37% of patients experienced ALP normalization after 12 months.
- Seladelpar reduced ALP levels by 44% on average from baseline.
- Reduction in pruritus was rapid and durable, with a mean reduction of 3.5 points at 6 months.
- No treatment-related serious adverse events were reported.
- Seladelpar was generally well tolerated, with a low discontinuation rate of 4.6%.
- FDA has accepted a New Drug Application for seladelpar with a priority review.
- Seladelpar also reduced other key liver markers: TB by 9%, GGT by 36%, and ALT by 25%.
- 19% of enrolled patients met the criteria for cirrhosis, indicating a more severe patient population.
- Most patients had a gap of one year or more between primary study completion and enrollment, potentially impacting results.
- Only 25% of patients achieved ALP normalization after 24 months.
- Seladelpar is still investigational and not approved by any regulatory authority.
Insights
Seladelpar shows promising efficacy in treating primary biliary cholangitis (PBC), a chronic liver disease. Clinical trials indicate substantial improvements in liver enzyme markers like alkaline phosphatase (ALP) and substantial relief from pruritus, a debilitating itch experienced by PBC patients. The drug appears well-tolerated with minimal adverse effects, providing hope in an area with limited treatment options.
The study's methodology—focusing on patients who have already participated in previous trials—lends robustness to the data, though the open-label design may introduce some bias. Long-term results will be key to confirming sustained efficacy and safety.
With both the U.S. FDA and European regulators reviewing Seladelpar, its future approval could mark a significant advancement in PBC treatment, addressing not just liver enzyme levels but also quality of life factors like itching.
The acquisition of CymaBay Therapeutics by Gilead Sciences aligns strategically with Gilead's existing focus on liver diseases. The positive interim results for Seladelpar could strengthen Gilead's portfolio, promising a new revenue stream if the drug gains regulatory approval in key markets.
Investors should note the short-term impact of potential FDA approval by August 2024, which if granted, could catalyze stock price appreciation. However, the long-term success depends on market penetration and acceptance by the medical community.
The priority review status by the FDA highlights the significant unmet need in PBC treatment, making Seladelpar a likely candidate for strong market uptake, assuming successful launch and real-world efficacy.
The market for primary biliary cholangitis (PBC) treatments is currently underserved, with few effective options available. If Seladelpar secures approval, it could capture a substantial share of this niche market, especially given its dual benefits in liver enzyme reduction and pruritus relief.
Understanding the competitive landscape is crucial: existing treatments like ursodeoxycholic acid (UDCA) have limitations and Seladelpar’s ability to address these could give it a competitive edge. The PBC market, while small, is likely to grow as awareness and diagnosis rates improve.
Healthcare providers may also favor a drug that offers comprehensive symptom relief. Consequently, Seladelpar's market entry could reshape treatment paradigms, benefiting patients and driving significant revenue for Gilead.
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- Reduction in Patient-Reported Pruritus (Itching) was Rapid and Durable in Patients with Moderate to Severe Symptoms -
- Positive Interim Results are Highly Consistent with Results from the Phase 3 RESPONSE Study of Seladelpar -
ASSURE is an open-label study evaluating the long-term safety and efficacy of seladelpar, a once daily potent and selective peroxisome proliferator-activated receptor (PPAR) delta agonist, or delpar. ASSURE enrolled adult patients with PBC who previously participated in a study of seladelpar where a key eligibility criterion included having an inadequate response or intolerance to ursodeoxycholic acid (UDCA). This interim data analysis did not include patients from the Phase 3 RESPONSE study, which will be reported separately. Of the 174 patients included, the majority had a gap of one year or more between completion of the respective primary study (seladelpar or placebo) and enrollment into ASSURE. Enrolled patients received an open-label oral dose of 10 mg seladelpar once daily, with the majority (
Most patients enrolled in ASSURE were female (
“We are encouraged by these positive interim results from ASSURE, which are highly consistent with those observed in the Phase 3, double-blind placebo-controlled RESPONSE study of seladelpar in people with an inadequate response or intolerance to UDCA,” said Cynthia Levy, M.D., Professor of Medicine, University of
Patient-reported pruritus was monitored throughout the study using the numerical rating scale (NRS; 0-10). In the 60 patients with moderate-to-severe pruritus at baseline with an NRS score of ≥4, a rapid improvement in pruritus was observed at Month 1. By Month 6 the patients reported a mean reduction of 3.5 points, and this impact was sustained through Month 12.
“The initial data from ASSURE further support the efficacy and safety profile of seladelpar observed across the robust development program and continue to indicate that seladelpar has the potential to be a best-in-class therapy that could help transform treatment for people living with primary biliary cholangitis,” said Merdad Parsey, Chief Medical Officer, Gilead Sciences. “The PBC community has been waiting for new treatments that help slow the progression of their liver disease as well as address difficult symptoms like pruritus that can have a significant impact on their quality of life. We are excited to offer a new option for this community as we work to bring seladelpar to people living with PBC, if approved.”
Additional results from ASSURE, including the long-term study of patients rolled over from RESPONSE to the ASSURE study, will be available at a future medical meeting.
A New Drug Application (NDA) for seladelpar for the treatment of PBC, including pruritus, in adults without cirrhosis or with compensated cirrhosis (Child Pugh A) who are inadequate responders or intolerant to UDCA, has been accepted for priority review by the
About ASSURE (NCT03301506)
ASSURE is an open label study to evaluate the long-term safety and tolerability of seladelpar in people with primary biliary cholangitis (PBC) who have already participated in other PBC clinical trials of seladelpar. The study is currently enrolling up to 500 people living with PBC from across 160 sites around the world. ASSURE will also address the long-term efficacy of seladelpar and its impact on important patient reported outcomes such as pruritus, or severe itch, which can have a significant impact on the quality of life of people living with PBC.
Interim results of ASSURE (Session #2060), titled “Efficacy and Safety of Seladelpar in Patients with Primary Biliary Cholangitis in the ASSURE Study: Interim Results,” will be presented Dr. Cynthia Levy on behalf of the ASSURE Study investigators during the DDW 2024 Presidential Plenary on May 18, 2024, from 8:00 am to 9:30 am EDT.
About Seladelpar
Seladelpar, an investigational treatment for people with PBC, is a first-in-class oral, selective PPAR-delta agonist, or delpar. PPAR-delta has been shown to regulate critical metabolic and liver disease pathways. Preclinical and clinical data support its ability to regulate genes involved in bile acid synthesis, inflammation, fibrosis and lipid metabolism, storage, and transport. Seladelpar is not approved by the FDA or any other regulatory authority globally and has not been determined to be safe or efficacious for any use.
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
About CymaBay
CymaBay Therapeutics Inc. was acquired by Gilead Sciences in March 2024. CymaBay Therapeutics, a Gilead Company, 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. Our deep understanding of the underlying mechanisms of liver inflammation and fibrosis, and the unique targets that play a role in their progression, helped CymaBay receive breakthrough therapy designation and orphan drug status from the
About Gilead Sciences in Liver Disease
For decades, Gilead has pioneered the way forward to improve the lives of people living with liver disease around the world. We have helped to transform hepatitis C from a chronic condition into one that can be cured for millions of people. For people living with hepatitis B or D, our focus on advancing our medicines drives hope that today’s research will turn into tomorrow’s cures. Beyond viral hepatitis, we’re working to deliver advanced treatments for people living with primary biliary cirrhosis (PBC). But our commitment doesn’t stop there. Through our ground-breaking science and collaborative partnerships, we strive to create healthier futures for everyone living with liver disease. We are committed to a future without liver disease.
About Gilead Sciences
Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19 cancer and inflammation. Gilead operates in more than 35 countries worldwide, with headquarters in
Forward-Looking Statements
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the ability of Gilead and CymaBay to initiate, progress or complete clinical trials within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical studies, including those involving seladelpar; the possibility that Gilead and CymaBay may make a strategic decision to discontinue development of programs for indications that are currently under evaluation and, as a result, these programs may never be successfully commercialized for such indications; uncertainties relating to regulatory applications and related filing and approval timelines, including the risk that the FDA, MHRA or EMA may not approve seladelpar the treatment of primary biliary cholangitis, and the risk that any such approvals, if granted, may be subject to significant limitations on use; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, as filed with the
Gilead and the Gilead logo are trademarks of Gilead Sciences, Inc. or its related companies.
For more information on Gilead’s commitment in Liver Disease please visit www.gilead.com.
For more information on investigational seladelpar and ASSURE please visit www.cymabay.com.
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Meaghan Smith, Media
public_affairs@gilead.com
Jacquie Ross, Investors
investor_relations@gilead.com
Source: Gilead Sciences, Inc.
FAQ
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