– 60% of Participants with Prior Fibrate or Obeticholic Acid Treatment Achieve Biochemical Response with Livdelzi –
– New Evidence Supports Livdelzi Delivers Clinically and Statistically Significant Improvements in Pruritus –
FOSTER CITY, Calif., May 07, 2025--(BUSINESS WIRE)--Gilead Sciences, Inc. (Nasdaq: GILD) today announced new data from multiple analyses which reinforce that Livdelzi® (seladelpar), known as Lyvdelzi® in the European Union, is effective and generally well-tolerated for the treatment of primary biliary cholangitis (PBC) and also provides sustained biochemical response in adults with PBC regardless of prior treatment history. Another analysis provides evidence supporting that Livdelzi delivered clinically and statistically significant improvements in pruritus. These data and more were presented at the European Association for the Study of the Liver (EASL) Congress 2025 in Amsterdam, Netherlands, from May 7–10.
Livdelzi Efficacy in Participants with Prior Fibrate or Obeticholic Acid Use
An interim analysis from ASSURE (NCT03301506), an ongoing, open-label, long-term study, reinforces the efficacy and safety profile of Livdelzi in people with PBC, including those with prior fibrate or obeticholic acid use. This analysis assesses participants from the pivotal Phase 3 placebo-controlled RESPONSE (NCT04620733) study and after participant rollover into the open-label ASSURE study, with or without prior fibrate or obeticholic acid use.
Among those with 18 months of exposure to Livdelzi, including 12 months in RESPONSE and 6 months in ASSURE, 60% (9/15) of participants with prior fibrate or obeticholic acid use achieved the composite biochemical response, as compared to 62% (54/87) of those without prior fibrate or obeticholic acid use. Among participants who started Livdelzi in ASSURE after previously receiving placebo in RESPONSE, 64% (7/11) of participants with prior fibrate or obeticholic acid use, as compared to 78% (32/41) of participants without prior fibrate or obeticholic acid use achieved the composite biochemical response after 6 months of receiving Livdelzi (Month 6 of ASSURE). Safety was similar regardless of prior fibrate or obeticholic acid use. No treatment-related serious adverse events (SAEs) were reported.
"Building on the momentum of Livdelzi’s launch, these new data presented at EASL further reinforce its potential as a meaningful treatment option for people living with PBC," said Dietmar Berger, MD, PhD, Chief Medical Officer, Gilead Sciences. "We are particularly encouraged by the sustained biochemical response seen with Livdelzi, even among those who previously received fibrates or obeticholic acid. These results strengthen the evidence supporting Livdelzi’s efficacy and tolerability across a broad population of patients, including those seeking alternatives to current therapies. We remain focused on addressing significant unmet needs and driving progress in liver health."
Livdelzi and Meaningful Change in Pruritus
Up to 80% of people with PBC experience symptoms such as pruritus (chronic itch) and fatigue, both of which can profoundly compromise quality of life. The Pruritus Numeric Rating Scale (NRS) can evaluate treatment effects to see if a therapy is working, as well as examine the meaningful within-person change (MWPC) in the Pruritus NRS that people with PBC with pruritus perceive as a beneficial treatment effect. Using anchor-based analyses, a new study of the qualitative data from the participants of the RESPONSE trial with moderate-to-severe pruritus (NRS ≥ 4) at baseline (n=72) provides evidence supporting that Livdelzi delivered clinically and statistically significant improvements in pruritus.
Results demonstrated that MWPC estimates of ≥ 3-points on the Pruritus NRS corresponded to "moderate improvement" as validated by PGI-C and 1-category improvement for PGI-S anchors. The data overall, including half of those interviewed (n=6/12), suggest a 3-point improvement in Pruritus NRS, as seen with seladelpar in the RESPONSE study, is a meaningful change. These findings highlight the potential of Livdelzi to address this debilitating symptom.
NRS scores were measured against two anchor analyses, the 7-day recall Patient Global Impression of Severity of pruritus (PGI-S) and the Patient Global Impression of Change of pruritus (PGI-C), which were administered at study visits. The MWPC threshold estimates were validated using distribution-based methods and empirical cumulative distribution function (eCDF) curves. Additionally, previously collected qualitative interviews were used to evaluate meaningful change on the Pruritus NRS in people with PBC with pruritus (NRS≥ 4) outside of the trial.
"Seladelpar is uniquely positioned as the only once-daily oral treatment that has statistically significant outcomes for both the underlying disease and the burdensome symptom of pruritus in people with PBC," said Alejandra Maria Villamil, MD, Chief of Autoimmune Liver Diseases Unit Hospital Italiano de Buenos Aires Buenos Aires, Argentina. "The demonstrated improvement in pruritus, combined with its established safety and efficacy profile, reinforces seladelpar as an on-label treatment option for people with PBC."
Expanding Global Access for the Treatment of PBC in EEA
Recently, the European Commission (EC) granted conditional marketing authorization for Lyvdelzi (seladelpar) for the treatment of PBC in combination with UDCA in adults who have an inadequate response to UDCA alone, or as monotherapy in those unable to tolerate UDCA. Lyvdelzi (an orphan designated product) provides an important treatment option for people living with the rare liver disease in the European Economic Area (EEA). Gilead is working with health authorities across Europe to ensure people living with PBC who are eligible for seladelpar have access as soon as possible. Lyvdelzi has been granted conditional marketing authorization in the EU. Continued approval of Lyvdelzi for the approved indication may be contingent on verification and description of clinical benefit in confirmatory trial(s).
Outside of the EEA, Livdelzi was granted accelerated approval by the U.S. Food and Drug Administration (FDA) in August 2024 and conditional approval by the UK Medicines and Healthcare products Regulatory Agency (MHRA) in January 2025.
Regulatory review for Livdelzi is also underway in Canada and Australia.
For more information on the EASL Congress 2025 and Gilead’s presentations, 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 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 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 ENHANCE (NCT03602560)
ENHANCE was a Phase 3, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of seladelpar in participants with primary biliary cholangitis (PBC) and an inadequate response or intolerance to UDCA. The trial investigated the potential of seladelpar to improve biochemical markers of liver function and reduce pruritus, and assessed safety. The ENHANCE study was terminated early due to reasons determined to be unrelated to Livdelzi.
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.
This indication is approved under accelerated approval based on a reduction of 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 (e.g., 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 seladelpar (such as the ASSURE, ENHANCE, 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; the risk that physicians may not see the benefits of prescribing seladelpar for treatment of PBC; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and factors are described in detail in Gilead’s Annual Report on Form 10-K for the year ended December 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 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).
