Positive Phase 3 IDEAL Study Results Further Support Livdelzi®’s (Seladelpar) Impact on Achieving ALP Normalization Goals in Second-Line Treatment Across a Broad Population of People Living with Primary Biliary Cholangitis (PBC)

FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced the detailed results from the Phase 3 IDEAL study, which demonstrated that the majority of participants living with PBC and treated with Livdelzi^® (seladelpar) achieved the alkaline phosphatase (ALP) normalization composite endpoint defined as a composite of ALP ≤ 1.0× upper limit of normal (ULN) and a ≥ 15% decrease from baseline. ALP is a key marker of disease activity and long-term outcomes in PBC. These results can expand understanding of treatment effects and inform evolving treatment goals for people living with PBC.

Key Highlights

• At Week 52, 75.4% (49/65) of participants who received Livdelzi achieved the ALP normalization composite endpoint versus 16.1% (5/31) of participants receiving placebo.
• Results will be presented at The Liver Meeting ^® 2026, hosted by the American Association for the Study of Liver Diseases (AASLD), November 5-9 in Denver, Colorado, and have been accepted for upcoming publication in the Journal of Hepatology.
• Gilead is engaging with global regulatory authorities to discuss these results.

IDEAL is a Phase 3, randomized, double‑blind, placebo‑controlled clinical study evaluating Livdelzi in adults living with PBC who have ALP levels above normal yet below the 1.67× ULN threshold typically required for inclusion in other PBC randomized controlled trials (RCTs). It is the first clinical trial to evaluate Livdelzi in people with inadequately controlled disease defined as ALP levels of 1-1.67× ULN despite receiving ursodeoxycholic acid (UDCA) for 12 months or with intolerance to UDCA.

“People with PBC whose alkaline phosphatase remains elevated but below 1.67 times the upper limit of normal have been largely excluded from previous pivotal trials of second-line therapies,” said Cynthia Levy, MD, University of Miami Miller School of Medicine. “IDEAL provides randomized, placebo-controlled evidence that seladelpar can improve biochemical response in this population. These findings can inform individualized treatment discussions, taking into account each individual’s risk of disease progression, symptoms, and potential benefits and risks of additional therapy.”

ALP is a key marker of disease activity with levels above normal associated with an increased risk of disease progression and poorer long-term outcomes, such as liver failure. Historically, the threshold for clinical study inclusion has been ALP levels >1.67× ULN. Recent clinical guidance recognizes ALP normalization as an ideal treatment goal in PBC. Results from IDEAL expand the evidence base by demonstrating that a significantly higher proportion of people with baseline ALP levels between 1-1.67× ULN and treated with Livdelzi can achieve ALP normalization compared to placebo. The response was evident after one month of treatment (52.3% versus 6.5% receiving placebo) and sustained through Week 52.

“The IDEAL study evaluated the impact of initiating second-line treatment in people living with PBC who have lower levels of baseline ALP elevation compared to prior clinical trials,” said Swati Tole, MD, MS, Senior Vice President, Clinical Development, Inflammation, Gilead Sciences. “A significantly greater proportion of people with elevated ALP levels, but below the threshold typically studied, achieved ALP normalization with Livdelzi, supporting ALP normalization as an achievable treatment goal. Together with the broader Livdelzi clinical program, IDEAL reinforces the importance of continuing to raise expectations for PBC care across a wide range of patients.”

The safety profile of Livdelzi observed in IDEAL was consistent with previously reported Livdelzi studies, with no new safety concerns identified. Adverse event incidence was generally similar between Livdelzi and placebo groups; serious adverse events occurred in 3.1% and 12.9% of individuals, respectively, and none were deemed related to trial drug.

About IDEAL (NCT06060665)

The IDEAL study was a Phase 3, double‑blind, placebo‑controlled trial designed to evaluate Livdelzi in adults living with primary biliary cholangitis (PBC) who have inadequately controlled disease, defined as having alkaline phosphatase (ALP) levels above normal but less than 1.67× ULN despite treatment with ursodeoxycholic acid (UDCA) or with UDCA intolerance. Its primary objective was to evaluate the effect of Livdelzi treatment at Week 52 compared to placebo, assessing rates of ALP normalization, defined as a composite of ALP ≤ 1.0× upper limit of normal (ULN) and ≥ 15% decrease from baseline in PBC participants with an ALP value greater than ULN but less than 1.67× ULN. A composite was used for the primary endpoint to ensure rigorous evaluation of ALP normalization over time. Exploratory endpoints included changes in other markers of cholestasis and liver injury. The study also evaluated the safety and tolerability of Livdelzi compared with placebo through Week 52. The study enrolled 96 adults aged 18–75 years.

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 living 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 reducing the risk of 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 improvement and normalization of alkaline phosphatase (ALP) levels, an important marker 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 potential anticholestatic, anti‑inflammatory, antipruritic, and antifibrotic effects.

Clinical trial data demonstrate that Livdelzi supports meaningful improvements in key markers of disease activity, including biochemical response and alkaline phosphatase (ALP) normalization, with sustained effects observed over long‑term follow‑up in multiple studies. These findings are supported by clinical studies evaluating Livdelzi in participants treated for up to 5 years.

Livdelzi has the potential to help address ongoing unmet needs for people living with PBC, including those who remain inadequately controlled on existing therapies. Pruritus is one of the most common and debilitating symptoms of PBC that can significantly impair quality of life. Clinical trial data have demonstrated 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). 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 (e.g., 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 Reaction

• The most common adverse reactions (≥5%) with LIVDELZI were headache (8%), abdominal pain (7%), nausea (6%), abdominal distension (6%), and dizziness (5%).

Drug Interactions

Potential Increased Exposure of LIVDELZI with:

• Probenecid: Avoid coadministration with LIVDELZI.
• Strong CYP2C9 Inhibitors: Monitor for adverse effects during concomitant use.
• Dual Moderate CYP2C9 and Moderate or Strong CYP3A4 Inhibitors (e.g., fluconazole): Monitor for adverse effects during concomitant use.
• CYP2C9 Poor Metabolizers Using Moderate or Strong CYP3A4 Inhibitors: Monitor for adverse effects during concomitant use of a moderate or strong CYP3A4 inhibitor in patients who are CYP2C9 poor metabolizers.
• Dual or Multiple Clinical Inhibitors of Drug Transporters OATP1B1, OATP1B3, and BCRP (e.g., cyclosporine): Monitor for adverse effects during concomitant use.

Potential Reduction in LIVDELZI Exposure with:

• Rifampin: Concomitant use of LIVDELZI with rifampin, an inducer of metabolizing enzymes, may result in delayed or suboptimal LIVDELZI biochemical response. Monitor biochemical response (e.g., ALP and bilirubin) when patients initiate rifampin during LIVDELZI treatment.
• 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. We have 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. But our commitment doesn’t stop there. Through ground-breaking science and collaborative partnerships, we strive to create healthier futures for everyone living with liver disease. Gilead remains 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.

In 2025, Gilead announced a $32 billion investment to further strengthen its U.S. footprint to power the next era of discovery, job creation and public health preparedness – while continuing to invest globally to ensure patients everywhere benefit from its scientific innovation. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, Calif.

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 IDEAL); 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; 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, 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.

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U.S. full Prescribing Information for Livdelzi^® is available at www.gilead.com.

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