June 05, 2024 02:00 AM Eastern Daylight Time

Gilead’s Seladelpar Demonstrated a Sustained and Consistent Long-Term Efficacy and Safety Profile in Primary Biliary Cholangitis

- Positive Results from Two-year Interim Analysis Includes Participants from Phase 3 RESPONSE Study and are Highly Consistent with One-year Interim Analysis -

- Reduction in Patient-Reported Pruritus (Itching) was Rapid and Durable in Participants with Moderate to Severe Symptoms -

- Subset Analysis of Participants with Compensated Cirrhosis Demonstrated Clinically Meaningful Improvements in Markers of Cholestasis and Liver Injury -

FOSTER CITY, Calif.--(BUSINESS WIRE)--Gilead Sciences, Inc. (Nasdaq: GILD), following the recent acquisition of CymaBay Therapeutics, Inc., today announced two-year interim results from the ongoing ASSURE study of investigational seladelpar for the treatment of primary biliary cholangitis (PBC), a rare, chronic inflammatory liver disease. The two-year interim analysis includes people living with PBC who participated in any prior clinical studies of seladelpar (legacy studies) and participants from the pivotal Phase 3 RESPONSE study. Results demonstrated rapid and sustained improvements in markers of cholestasis, including high rates of normalization of liver biomarkers and a clinically meaningful reduction in pruritus (itch). These most recent data were shared in a presentation during the European Association for the Study of the Liver (EASL) Congress 2024 in Milan, Italy.

“The data presented at EASL further support the sustained efficacy and safety profile of seladelpar observed across its robust development program, including a capacity to normalize ALP values for many of the people studied with PBC. Given ALP is recognized as an important surrogate marker of disease progression in PBC, providers are shifting to normalization as a treatment goal, which could potentially be enabled by seladelpar, if approved,” said Timothy Watkins, MD, MSc, Vice President, Clinical Development of Inflammation Therapeutics, Gilead Sciences. “Seladelpar is a potential best-in-class therapy that could transform the treatment landscape for people living with PBC by not only improving or even normalizing markers of liver function, but also improving pruritis or itch. Pruritis is a particularly burdensome symptom of PBC which can significantly disrupt a person’s quality of life. We’re committed to transforming the management of PBC and the lives of those impacted by this rare disease as we work together to bring seladelpar to the community, if approved.”

ASSURE is an open-label, long-term Phase 3 study evaluating the safety and efficacy profile of seladelpar, a potent, selective, orally active delpar, or selective peroxisome proliferator-activated receptor delta (PPAR) agonist, in adults with PBC. Participants received 10 mg seladelpar, once daily, for up to 155 weeks in the current analysis of the ASSURE cohort. The two-year interim analysis, with a data cutoff date of January 31, 2024, included 179 participants from legacy studies and 158 participants from the Phase 3 registrational RESPONSE study. Of the 99 participants from legacy studies completing 24 months of treatment with seladelpar, 70% met the composite response endpoint, which includes alkaline phosphatase (ALP) levels below 1.67 x the upper limit of normal (ULN), a decrease in ALP levels of at least 15%, and total bilirubin (TB) levels at or below the ULN. In addition, 42% of these participants achieved ALP normalization at 24 months, a marker of liver disease progression. For the 164 participants from legacy studies completing 12 months of treatment with seladelpar, 73% achieved the clinically meaningful composite response endpoint, with 42% experiencing ALP normalization.

“Currently, there is no cure for PBC. While there are lifelong medicines that may slow liver damage and stop it from progressing, current medications fall short in about 40% of people. This is because many individuals continue to have abnormal liver tests on the current treatment options, and these treatments don’t reduce one of the main relentless symptoms, pruritis, which impacts the quality of life in people living with PBC,” said Dr. Palak Trivedi, BSc, MBBS, MRCP, PhD, Professor of Associate Professor and Consultant Hepatologist, University of Birmingham, and presenter of the study. “The long-term efficacy and safety interim results from ASSURE demonstrate that seladelpar may meaningfully raise the bar in PBC. Seladelpar can help people achieve significant reduction, and in some cases, normalization of liver blood tests. At the same time, seladelpar can also help lower itch intensity.”

For those participants who completed the 12-month RESPONSE study after randomization to seladelpar, who continued into the ASSURE study and received continuous seladelpar treatment for a total of 18 months (12 months in RESPONSE, six months in ASSURE, n=102), 62% achieved the composite response endpoint, and 33% reached ALP normalization. For participants who received seladelpar for 24 continuous months (n=29), 72% and 17% met the composite response endpoint and ALP normalization, respectively. Additional study findings demonstrate that of the 52 participants previously randomized to placebo in the RESPONSE study, 75% met the composite response endpoint, and 27% achieved ALP normalization following cross-over to six months of treatment with seladelpar in ASSURE. Following 12 months of treatment, 94% of those crossing over met the composite response endpoint, and 50% reached ALP normalization (n=16). Across all ASSURE participants, the safety profile was favorable and generally well-tolerated with long-term use, with no treatment-related serious adverse events as determined by the study investigators. These results are similar to the results seen in an earlier data cut presented at Digestive Disease Week last month.

Patient-reported pruritus was also collected throughout the ASSURE study using the numerical rating scale (NRS; 0-10). Among the participants with baseline NRS≥4, sustained improvement in pruritus was observed with a mean reduction of 3.8 and 3.1 points at 12 and 24 months in participants from legacy studies, respectively. For RESPONSE participants, a mean reduction of 3.8 was observed in both continuous and former placebo participants at six months in the ASSURE study. These findings were consistent with the results observed in the pivotal RESPONSE study, reinforcing the durability of this treatment effect.

Interim results of a subset of participants with liver cirrhosis from the open-label, long-term ASSURE safety study will be shared as an oral presentation at EASL (Presentation ID: OS-019). These participants with compensated cirrhosis, received a second year of seladelpar treatment following their initial participation in the Phase 3 RESPONSE study. Consistent with the results of the RESPONSE trial, participants achieved clinically meaningful improvements in markers of cholestasis and liver injury.

Among participants with compensated liver cirrhosis from legacy studies who enrolled in the ASSURE study (n=35), 91% were female with a mean age of 60.8 years. Additionally, 23% (8/35 participants) had portal hypertension, 89% were Child-Pugh (CP) class A, and 11% were CP-B. At baseline, mean ALP was 245 U/L, TB was 1.0 mg/dL (31% > ULN), and mean liver stiffness measure assessed by FibroScan was 19.9 kPa. As of the data cutoff date (January 31, 2024), 32 participants with compensated cirrhosis had completed 12 months of treatment. Of those participants, 56% (18/32) met the composite biochemical endpoint at Month 12, with ALP normalization occurring in 47% (15/32 participants). No serious adverse events were related to the study drug as determined by the study investigators.

A New Drug Application (NDA) for seladelpar for the treatment of primary biliary cholangitis, including pruritus, in adults without cirrhosis or with compensated cirrhosis (Child-Pugh A) who are inadequate responders or intolerant to ursodeoxycholic acid (UDCA), has been accepted for priority review by the U.S. Food and Drug Administration (FDA) with an anticipated decision in August 2024. The U.K. Medicines and Healthcare Products Regulatory Agency (MHRA) and the European Medicines Agency (EMA) have also accepted seladelpar for review.

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 assess the long-term efficacy of seladelpar and its impact on important patient reported outcomes such as cholestatic pruritis, or itch, which can have a significant impact on the quality of life of people living with PBC.

Participants enrolled in ASSURE at the time of this interim data analysis include participants from previous studies of seladelpar in PBC, including the Phase 3 registrational RESPONSE study and the other clinical trials, which include the Phase 2 dose-ranging study, the Phase 3/4 long-term open label study and the Phase 3 ENHANCE program that were both terminated early, and the ongoing open label study in people with PBC and hepatic impairment. The majority of participants from the legacy studies have a gap of one year or more off-treatment before enrollment in the study, and 19% of participants had cirrhosis. Participants received an open-label daily dose of 10 mg of seladelpar orally for up to 155 weeks in ASSURE.

Interim results of ASSURE (Abstract #LB-283), titled “Long-term efficacy and safety of open-label seladelpar treatment in patients with primary biliary cholangitis (PBC): Interim results for 2 years from the ASSURE study,” will be presented Dr. Palak Trivedi on behalf of the ASSURE study investigators during the EASL 2024 Congress on June 5, 2024.

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 and fatigue, which can be debilitating for some people. 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 (such as the ASSURE and RESPONSE trials); uncertainties relating to regulatory applications and related filing and approval timelines, including the risk that the FDA and other regulatory authorities may not approve seladelpar for the treatment of PBC, and the risk that any such approvals, if granted, may be subject to significant limitations on use; 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; 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.

CymaBay, the CymaBay logo, and GILEAD 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.