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Gilead’s Livdelzi® Demonstrates Sustained Efficacy in Primary Biliary Cholangitis (PBC), Offering Alkaline Phosphatase (ALP) Reduction, Itch Relief and Potential to Slow Disease Progression

via Business Wire

– New Data Exclusive to Livdelzi Highlights its Potential as an Effective and Well-Tolerated Option for PBC Patients Switching from Obeticholic Acid –

– Analysis of Phase 3 ASSURE Study Finds Livdelzi Shows Promising Data on Liver Stiffness in PBC Patients After 3 Years –

– Livdelzi Data in PBC Participants Provide Outcomes for Long-Term Biochemical Response, which Slows Disease Progression and Sustained Reductions in Chronic Itch, which Impacts Patient Wellbeing and Quality of Life –

Gilead Sciences, Inc. (Nasdaq: GILD) today announced new long-term data reinforcing the safety and efficacy profile of Livdelzi® (seladelpar) for people living with primary biliary cholangitis (PBC). Findings support Livdelzi's consistent efficacy and safety outcomes in patients switching from obeticholic acid and positive impact on liver stiffness over 3 years. These findings were presented at The Liver Meeting® hosted by the American Association for the Study of Liver Diseases (AASLD) 2025 in Washington, D.C. (November 7–11).

Late-breaking, real-world data on Livdelzi, the only PBC treatment that provides statistically significant reductions across key biomarkers of disease and itch vs. placebo, support Livdelzi as an effective and well-tolerated alternative for patients switching from obeticholic acid, and as a second-line therapy. Among 396 patients analyzed, 130 switched from obeticholic acid and 266 used Livdelzi as second-line or monotherapy based on data available since US approval in late 2024. Reductions in alkaline phosphatase (ALP) were observed in both groups, with most patients achieving ALP levels below 1.67×ULN. Safety labs remained stable, and 93% of patients continued Livdelzi treatment throughout the observation period.

"These real-world findings offer encouraging evidence that seladelpar is a viable alternative to obeticholic acid and promising second-line therapy for patients with PBC," said Christopher L. Bowlus, MD, FAASLD, Lena Valente Professor and Chief of the Division of Gastroenterology and Hepatology at the University of California Davis School of Medicine. "ALP is our primary measure of treatment efficacy and the improvements in ALP, across both switch and second-line groups, are clinically meaningful. The safety profile and treatment continuity further support the use of seladelpar for the treatment of patients who previously had limited options.”

Gilead will present late-breaking interim results from its Phase 3 ASSURE study (NCT03301506), showing Livdelzi’s potential to improve liver health in people with PBC. After up to three years of treatment, 85% of participants maintained or improved their liver stiffness measurements (LSMs). Among 114 participants with data at Month 36, the median change from baseline was −0.2 kPa (−2.9%). Notably, those in the highest-risk group (baseline LSM ≥16.9 kPa) saw a median reduction of −5.2 kPa (−29.7%). These findings build on data shared at The Liver Meeting 2024 and underscore Livdelzi’s role in addressing this progressive and underrecognized disease.

“These data presented at The Liver Meeting underscore Livdelzi’s potential to meaningfully alter the trajectory of PBC by addressing liver stiffness, a key marker of disease progression,” said Dietmar Berger, MD, PhD, Chief Medical Officer at Gilead Sciences. “In this interim analysis of the ASSURE study, patients treated with Livdelzi for up to 3 years demonstrated stability or improvement in liver stiffness, with the greatest benefit observed in those at highest risk. This reinforces our belief in Livdelzi’s treatment profile and its potential to help transform care for people living with PBC. At Gilead, we remain focused on delivering innovation that drives long-term impact for patients and the healthcare community.”

ASSURE Demonstrates Livdelzi’s Sustained Efficacy Outcomes Through Three Years and Safety Through Four Years

New interim results from the open-label Phase 3 ASSURE trial show that 67% (82/122) of participants with PBC achieved a composite biochemical response (CBR), while 34% (41/122) reached normalized ALP levels after three years of treatment with Livdelzi. These results are consistent with those from the pivotal Phase 3 RESPONSE trial and underscore Livdelzi’s potential to meaningfully impact disease progression and pruritus symptom burden in PBC. Livdelzi continues to show a robust safety profile, with no treatment-related serious adverse events (SAEs) and no new safety signals after up to four years of exposure. These findings align with the efficacy and safety results from the two and half year efficacy and three year safety interim results presented at The Liver Meeting 2024.

Livdelzi Impact on Pruritus in PBC Patients

New data from the pivotal RESPONSE study (NCT04620733) and its open-label extension, ASSURE, show that Livdelzi delivers sustained and meaningful reduction in chronic itch—a debilitating symptom affecting up to 80% of people with PBC. Among patients with moderate to severe itch at the start of treatment, over half reported significant improvement, including those who switched from placebo. Benefits were maintained for up to 30 months and supported with validated patient-reported measures such as the pruritus NRS, 5-D Itch, and PBC-40 Itch domain scores. Notably, the pruritus numeric rating scale (NRS) used throughout both studies underwent rigorous psychometric validation, demonstrating its reliability and sensitivity to change in the open-label ASSURE study – reinforcing Livdelzi’s long-term efficacy profile.

Additional analysis from RESPONSE showed that Livdelzi not only reduced itch severity but also impacted the burden itch places on daily life, including the ability to engage in social activities, complete household tasks, and participate in work or school. It also reduced the spread of itch across the body. A separate analysis suggests that Livdelzi may offer meaningful improvements in PBC-related itch, which can impact quality of life for people living with this chronic condition, not just those experiencing moderate or severe itch.

Gilead Commitment to Advocacy

Gilead, in collaboration with Viver Health and leading PBC advocacy groups, launched Your Guide to Living Well with Primary Biliary Cholangitis, a patient-centered resource designed to improve quality of life for those living with PBC. Co-created with patients, advocates, and healthcare providers, the guide offers practical strategies for symptom management and shared decision-making. Early feedback, being presented at The Liver Meeting, highlights its value in empowering patients and filling a critical gap in disease education. This initiative reflects Gilead’s ongoing commitment to supporting the PBC community — a commitment also embodied in efforts like the All the Feelings with PBC™ campaign, which amplifies the emotional realities of living with PBC through storytelling and advocacy.

For more information, including a complete list of abstract titles being presented at the meeting, please visit the AASLD website.

Livdelzi was granted accelerated approval by the U.S. Food and Drug Administration (FDA) in August 2024.

Please see below for U.S. Indication and Important Safety Information for Livdelzi.

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 ongoing open label study in people with PBC and hepatic impairment.

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). 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 help 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 up to 80% of people with PBC can experience and can 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 slowing disease progression and reducing the symptoms related to cholestasis (impaired bile flow), such as cholestatic itch. The effect is primarily measured by an improvement in liver biochemical tests, including the normalization of alkaline phosphatase (ALP) levels, an important marker of disease progression in PBC.

About Livdelzi

Livdelzi is an oral PPAR-delta agonist, or delpar, for the treatment of PBC. PPAR-delta has been shown to regulate critical metabolic and liver disease pathways. Preclinical and clinical data indicate Livdelzi has anticholestatic, anti-inflammatory, antipruritic, and antifibrotic effects.

Livdelzi has potential to help meet the current unmet need of people living with PBC, as the first and only treatment that achieved statistically significant improvements across biochemical response, ALP normalization, and pruritus versus placebo. Pruritus is a common symptom that can significantly impair quality of life in people with PBC.

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). 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 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 Livdelzi (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 Livdelzi; 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; 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 September 30, 2025, 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, 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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