Investigational Seladelpar Demonstrates Significant Improvements in Liver Disease Progression and Reduced Itching in Primary Biliary Cholangitis

FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD), following the recent acquisition of CymaBay Therapeutics, Inc., today announced interim results from the ongoing ASSURE study demonstrating treatment with seladelpar, an investigational PPAR delta agonist, led to improvements in markers of cholestasis and reduced inflammation. Additional findings demonstrate that seladelpar can help reduce pruritus (itch) in people living with primary biliary cholangitis (PBC). There are currently no treatments indicated to treat PBC-related pruritis. This data will be shared in an oral presentation during the Presidential Plenary of the Digestive Disease Week^® 2024 Conference in Washington, DC.

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 (97%) also receiving UDCA treatment.

Most patients enrolled in ASSURE were female (94%), with a mean age of 59 years. Baseline characteristics included mean alkaline phosphatase (ALP) 270.5 U/L and total bilirubin (TB) 0.75 mg/dL; 19% of enrolled patients met the criteria for cirrhosis. The study evaluated several prespecified biochemical endpoints, including the composite response of an alkaline phosphatase (ALP) below 1.67 x upper limit of normal (ULN), a decrease in ALP of at least 15%, and a total bilirubin (TB) below the ULN. Endpoints were evaluated over an interim observation period extending from enrollment through a data cutoff date of June 29, 2023, with the majority of those (85%) having at least 12 months of continuous treatment with seladelpar. Seventy percent of the 148 patients who completed 12 months of treatment achieved the clinically meaningful composite response endpoint. Among those receiving seladelpar, 37% experienced ALP normalization, with a mean ALP change from baseline of -44% (-144.4 U/L). Of the 20 patients who completed 24 months of treatment, 70% achieved the composite response endpoint and 25% experienced ALP normalization. Seladelpar also reduced other important biomarkers of liver injury including TB, gamma-glutamyl transferase (GGT) and alanine aminotransferase (ALT) levels by 9%, 36%, and 25% from baseline, respectively. There were no treatment-related serious adverse events in the study, as determined by the study investigators. Seladelpar was generally well tolerated, with discontinuation due to adverse events occurring in 4.6% of patients.

“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 Miami and presenter of the study. “Seladelpar continues to demonstrate a significant impact on PBC disease in the liver, helps a significant proportion of patients achieve normalization of their ALP and importantly reduces pruritus, which is often a debilitating and unrelenting comorbidity. The safety and tolerability profile of seladelpar is consistent with previous studies in PBC and underscores its potential as a promising therapeutic option for people living with PBC.”

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 U.S. Food and Drug Administration (FDA) with an anticipated decision in August 2024. Seladelpar has also been accepted for review by the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA).

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 U.S.). 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 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 U.S. Food and Drug Administration for seladelpar, a first-in-class investigational treatment for people with PBC.

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 Foster City, California.

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 U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties, and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead and CymaBay, and Gilead and CymaBay assume no obligation and disclaim any intent to update any such forward-looking statements.

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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 .