– ALP Is a Key Marker of Disease Activity in People Living With PBC, With Elevations Above Normal Associated with Increased Risk of Disease Progression –
– Further Analyses of the Phase 3 ASSURE Study Demonstrate Sustained ALP Normalization and Show Exploratory Outcomes of Stable or Improved Liver Stiffness, Providing Supportive, Long-term Evidence –
FOSTER CITY, Calif.--(BUSINESS WIRE)--Gilead Sciences, Inc. (Nasdaq: GILD) today shared new results from a post hoc analysis showing that Livdelzi® (seladelpar) was associated with high and sustained rates of normalization of a key liver marker (ALP) in people living with primary biliary cholangitis (PBC). In an ongoing Phase 3 study, participants with elevated ALP levels (between 1.0 and 1.67×ULN) experienced reductions in ALP after treatment. These data highlight the potential role of Livdelzi in people with PBC who continue to have elevated ALP despite prior treatment with first-line therapy.
These findings are highly relevant for people living with PBC with inadequately controlled disease based on elevated ALP levels—a population historically underrepresented in randomized clinical trials. The data will be presented at the European Association for the Study of the Liver (EASL) Congress 2026, held May 27–30 in Barcelona, Spain.
“Achieving ALP normalization is increasingly recognized as a key treatment goal in PBC due to its association with improved long‑term clinical outcomes,” said Cynthia Levy, MD, Professor of Medicine in the Division of Digestive Health and Liver Diseases, and Associate Director of the Schiff Center for Liver Diseases at the University of Miami. “These data show that seladelpar can help people who have not reached ALP normalization achieve this important biochemical target and support its potential role across a broader range of people living with PBC, including those with lower ALP levels.”
ASSURE is an ongoing, open‑label Phase 3 study evaluating the long‑term safety and efficacy of Livdelzi in people living with PBC who previously participated in Livdelzi clinical trials. In an interim post hoc analysis, a high and sustained reduction in ALP was observed with Livdelzi treatment in participants with elevated baseline ALP levels between 1.0 and 1.67×ULN. Among 50 participants, 83% of evaluable participants achieved composite ALP normalization—defined as ALP ≤1×ULN with ≥15% reduction—at 12 months, and 74% achieved the same endpoint at 24 months, demonstrating a persistent response over two years of treatment.
Mean ALP levels declined substantially from baseline and remained reduced through long‑term follow‑up. Improvements were also observed in other markers of cholestasis, including gamma‑glutamyl transferase (GGT), and total bilirubin remained stable overall.
This population included individuals with recognized risk factors for disease progression, including cirrhosis and younger age at diagnosis. Livdelzi was found to be generally well tolerated, with no treatment discontinuations due to adverse events with up to two years of follow-up and no new safety signals observed, consistent with previously reported findings.
Separately, in an exploratory analysis across the full ASSURE population, 85% (n=77/91) of participants who achieved biochemical response at 12 months and were followed up through 3 years maintained or improved liver stiffness measurements. Liver stiffness stability is a commonly used non‑invasive marker associated with long‑term outcomes and is descriptive in nature in this open‑label analysis.
“The data presented add to the growing body of clinical evidence supporting the role of Livdelzi as a therapeutic approach for people living with PBC,” said Swati Tole, MD, MS, Clinical Development, Inflammation at Gilead Sciences. “Combining ALP normalization with effective symptom management provides a more holistic approach to care. With Livdelzi, we aim to address both—helping improve pruritus, one of the most debilitating symptoms of PBC, and normalize ALP, a key marker of disease progression risk—supporting a comprehensive approach to disease management.”
Additional interim analyses from the ASSURE and pivotal RESPONSE studies help support the long‑term efficacy and safety profile of Livdelzi across a broad range of people living with PBC. These findings build on the results shared at The Liver Meeting 2025 and further support its potential to contribute to sustained clinical benefit in both broad and high‑risk PBC populations.
Livdelzi (seladelpar) is approved for use for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA alone, or as monotherapy in those unable to tolerate UDCA in the United States (U.S.), United Kingdom (UK), Australia and Israel, as well as the European Economic Area (EEA), Switzerland and Canada where it is marketed as Lyvdelzi.
For more information on the EASL Congress 2026 and Gilead’s data presented, please visit the congress website.
About ASSURE (NCT03301506)
ASSURE is an open-label, long-term study to evaluate the safety and tolerability of Livdelzi in people with primary biliary cholangitis (PBC) who have already participated in other PBC clinical trials of Livdelzi. The ASSURE study includes participants from previous studies of Livdelzi in PBC, including the Phase 3 registrational RESPONSE study and legacy clinical trials. Legacy studies include the open label Phase 2 dose-ranging study (2 mg, 5 mg, or 10 mg Livdelzi), the open label Phase 3/4 long-term safety study (5 mg or 10 mg Livdelzi), the Phase 3 placebo-controlled ENHANCE study (5 mg or 10 mg Livdelzi vs placebo), and the PBC and hepatic impairment study for Livdelzi.
About RESPONSE (NCT04620733)
RESPONSE was a pivotal Phase 3, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy and safety of Livdelzi in adults with primary biliary cholangitis (PBC) who have shown inadequate response or intolerance to ursodeoxycholic acid (UDCA) defined by an ALP >= 1.67x ULN. The trial enrolled 193 participants across multiple sites worldwide. RESPONSE assessed the key biomarker of cholestasis alkaline phosphatase (ALP) and other parameters of liver function, as well as secondary endpoints including pruritus and other patient quality of life measurements.
Participants in the RESPONSE trial received a daily oral dose of 10 mg of Livdelzi for 12 months. The trial aimed to address the high unmet need for effective second-line therapies for individuals with PBC. The approvals of Livdelzi were based primarily on data from the RESPONSE study.
About PBC
PBC is a chronic, autoimmune disease of the bile ducts that affects approximately 130,000 Americans. PBC is more common in women and causes liver damage that can progress to liver failure and result in the need for liver transplant, if left untreated. The most common symptoms of PBC are pruritus (chronic itch) and fatigue, which many people living with PBC can experience and may profoundly compromise quality of life. Symptoms of PBC are often invisible to others, and the journey to a PBC diagnosis can be long and challenging.
There is currently no cure for PBC, and treatment goals include reducing the risk of disease progression and reducing symptoms related to cholestasis (impaired bile flow), such as cholestatic itch.
Treatment effect is primarily assessed through liver biochemical tests, including improvements in alkaline phosphatase (ALP), an important marker of disease activity associated with long‑term outcomes in PBC.
About Livdelzi
Livdelzi (seladelpar) is an oral PPAR‑delta agonist, or delpar, for the treatment of primary biliary cholangitis (PBC). PPAR‑delta is known to regulate key metabolic and liver disease pathways. Preclinical and clinical data indicate that Livdelzi has anticholestatic, anti‑inflammatory, antipruritic, and antifibrotic effects.
Clinical trial data demonstrate that Livdelzi improves key markers associated with disease activity, including biochemical response and alkaline phosphatase (ALP) normalization, with sustained effects observed over long‑term follow‑up. These findings are supported by clinical studies evaluating Livdelzi in hundreds of participants treated for up to five years.
Livdelzi addresses ongoing unmet needs for people living with PBC, including those who remain inadequately controlled on existing therapies. Pruritus is a common symptom of PBC that can significantly impair quality of life, and prior studies have shown statistically significant and clinically meaningful improvements in pruritus with Livdelzi compared with placebo.
U.S. Indication for Livdelzi
Livdelzi is indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have had an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. The FDA approved this indication under accelerated approval based on a reduction of alkaline phosphatase (ALP). Improvement in survival or prevention of liver decompensation events have not been demonstrated. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
Limitations of Use:
Use of Livdelzi is not recommended in patients who have or develop decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy).
U.S. Important Safety Information for LIVDELZI
Warnings and Precautions
- Fractures: Fractures occurred in 4% of LIVDELZI-treated patients compared to no placebo-treated patients. Consider the risk of fracture in the care of patients treated with LIVDELZI and monitor bone health according to current standards of care.
- Liver Test Abnormalities: LIVDELZI has been associated with dose-related increases in serum transaminase (AST and ALT) levels > 3 x ULN in patients receiving 50 mg and 200 mg once daily (5x and 20x higher than the recommended dosage of 10 mg once daily). Transaminase levels returned to pretreatment levels upon LIVDELZI discontinuation. In the pivotal RESPONSE study, LIVDELZI 10 mg once daily did not show a similar pattern for increases in transaminase levels Perform baseline clinical and laboratory testing when starting LIVDELZI and monitor thereafter according to routine patient management. Interrupt treatment if the liver tests (ALT, AST, total bilirubin, and/or ALP) worsen, or if the patient develops signs and symptoms of clinical hepatitis (eg, jaundice, right upper quadrant pain, eosinophilia). Consider permanent discontinuation if liver tests worsen after restarting LIVDELZI.
- Biliary Obstruction: Avoid use of LIVDELZI in patients with complete biliary obstruction. If biliary obstruction is suspected, interrupt LIVDELZI and treat as clinically indicated.
Adverse Reactions
- The most common adverse reactions (≥5%) with LIVDELZI were headache (8%), abdominal pain (7%), nausea (6%), abdominal distension (6%), and dizziness (5%).
Drug Interactions
- OAT3 Inhibitors and Strong CYP2C9 Inhibitors: Avoid coadministration with LIVDELZI due to increased LIVDELZI exposure.
- Rifampin: Monitor biochemical response (e.g., ALP and bilirubin) when patients initiate rifampin during LIVDELZI treatment. Coadministration may result in delayed or suboptimal biochemical response of LIVDELZI.
- Dual Moderate CYP2C9 and Moderate-to-Strong CYP3A4 Inhibitors and BCRP Inhibitors (eg, cyclosporine): Monitor closely for adverse effects. Concomitant administration with LIVDELZI may increase LIVDELZI exposure.
- CYP2C9 Poor Metabolizers Using Moderate-to-Strong CYP3A4 Inhibitors: Monitor more frequently for adverse reactions as concomitant use of a moderate-to-strong CYP3A4 inhibitor in patients who are CYP2C9 poor metabolizers may increase LIVDELZI exposure and risk of LIVDELZI adverse reactions.
- Bile Acid Sequestrants: Administer LIVDELZI at least 4 hours before or 4 hours after taking a bile acid sequestrant, or at as great an interval as possible.
Pregnancy and Lactation
- Pregnancy: There are insufficient data from human pregnancies exposed to LIVDELZI to allow an assessment of a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Report pregnancies to Gilead Sciences, Inc., at 1-800-445-3235.
- Lactation: There are no data on the presence of LIVDELZI in human or animal milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for LIVDELZI and any potential adverse effects on the breastfed infant from LIVDELZI.
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. The company has helped to transform hepatitis C from a chronic condition into one that can be cured for millions of people. For individuals living with hepatitis B or D, Gilead's focus on advancing medicines drives hope that today’s research will turn into tomorrow’s cures. Beyond viral hepatitis, Gilead is working to deliver advanced treatments for people living with PBC. The commitment of Gilead doesn’t stop there. Through ground-breaking science and collaborative partnerships, the company strives to create healthier futures for everyone living with liver disease. Gilead remains devoted 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 Gilead’s ability 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 trials, including those involving seladelpar (such as the ASSURE, RESPONSE and any confirmatory studies); uncertainties relating to regulatory applications and related filing and approval timelines, including additional pending and potential applications for seladelpar; the risk that any regulatory approvals, if granted, may be subject to significant limitations on use or subject to withdrawal or other adverse actions by the applicable regulatory authority; uncertainties regarding Gilead’s ability to coordinate access to seladelpar in a timely manner or at all; 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, 2026, 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 Gilead assumes no obligation and disclaims any intent to update any such forward-looking statements.
Livdelzi, Lyvdelzi, Gilead and the Gilead logo are registered trademarks of Gilead Sciences, Inc., or its related companies.
U.S. full Prescribing Information for Livdelzi is available at www.gilead.com.
For more information about Gilead, please visit the company’s website at www.gilead.com, follow Gilead on X/Twitter (@Gilead Sciences) and LinkedIn (@Gilead-Sciences).
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