Gilead’s Seladelpar Granted Conditional European Marketing Authorization for the Treatment of Primary Biliary Cholangitis

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02/20/2025 - 04:30 PM

– Now Approved, Seladelpar Can Provide an Important Treatment Option for People Living With the Rare Liver Disease in the European Economic Area –

– First and Only Treatment That Achieved Statistically Significant Improvements Across Biochemical Response, Alkaline Phosphatase Normalization, and Pruritus Versus Placebo –

FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the European Commission (EC) has granted conditional marketing authorization for seladelpar 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. Seladelpar (an orphan designated product) is now approved and will provide an important treatment option for people living with the rare liver disease in the European Economic Area (EEA).

“Today’s decision reinforces the clinical benefit and value of seladelpar and offers people living with PBC in Europe an important new treatment option,” said María-Carlota Londoño, MD, PhD, Hepatologist at Hospital Clinic Barcelona. “There are people in Europe who do not have an adequate response to first-line therapy and seladelpar helps address the unmet need for effective and symptom-directed treatment.”

PBC is a rare, chronic, autoimmune disease of the bile ducts that affects approximately 22 out of 100,000 people in Europe. PBC is more common in women and causes liver damage that can progress to liver failure, particularly if left untreated. The most common symptoms of PBC are pruritus (chronic itch) and fatigue, which can be debilitating for some people. 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.

“People living with PBC in Europe have been waiting for treatment advancements for many years. Up until now, there has been no approved treatment for PBC addressing both the surrogate biomarkers for underlying disease and pruritus, a common and at times debilitating symptom of PBC. That changes today with the conditional approval of seladelpar, which has been shown to both help treat the disease and reduce pruritus,” said Timothy Watkins, MD, MSc, Vice President, Clinical Development of Inflammation Therapeutics, Gilead Sciences. “We look forward to working with health authorities across Europe to bring this promising new treatment to all those who could benefit.”

The EC’s decision follows the positive opinion of the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) in December 2024, and is primarily based on results from the pivotal placebo-controlled Phase 3 RESPONSE study. In the study, 62% of participants taking seladelpar achieved the primary endpoint of composite biochemical response at Month 12, versus 20% of participants taking placebo. Treatment with seladelpar led to normalization of ALP values in 25% of trial participants at Month 12. This change was not seen in any trial participants receiving placebo. Change from baseline pruritus score at Month 6 was a key secondary endpoint; patients treated with seladelpar demonstrated a statistically significant reduction in pruritus compared with placebo. After six months of treatment with seladelpar, participants entering the study with moderate to severe itch experienced a 3.2-point improvement on a pruritus numerical rating scale of 0-10, a clinically meaningful improvement, compared to a decrease of 1.7 points with placebo. There were no treatment-related serious adverse events, as determined by study investigators. The most common adverse events, occurring in ≥ 5% of participants in the seladelpar arm and at an incidence of ≥ 1% higher than in the placebo arm were headache, nausea, abdominal pain, and abdominal distension.

Gilead is now working with health authorities across Europe to ensure people living with PBC who are eligible for seladelpar have access as soon as possible. Seladelpar has been granted conditional marketing authorization in the EU. Continued authorization of seladelpar for the approved indication will be contingent on verification and description of clinical benefit in confirmatory trial(s). Outside of the EEA, seladelpar was granted accelerated approval by the U.S. Food and Drug Administration (FDA) in August 2024. Most recently, seladelpar received approval by the UK Medicines and Healthcare products Regulatory Agency (MHRA) in January 2025. Regulatory review is also underway in Canada and Australia.

About RESPONSE (NCT04620733)

RESPONSE is a Phase 3, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy and safety of seladelpar in adults with PBC who have shown inadequate response or intolerance to first-line treatment with UDCA. The trial enrolled 193 participants across multiple sites worldwide. RESPONSE assessed key biomarkers of cholestasis, including ALP levels, as well as secondary endpoints related to liver function and patient quality of life.

Participants in the RESPONSE trial received a daily oral dose of 10 mg of seladelpar or placebo for 12 months, with a focus on measuring changes in ALP and other relevant liver function tests. The trial aimed to address the high unmet need for effective second-line therapies for individuals with PBC, providing important insights into the long-term management of this chronic liver disease.

About PBC

PBC is a rare, chronic inflammatory liver disease that affects approximately 163,000 people in Europe. It primarily affects women (1 in 1,000 women over the age of 40 globally). PBC is characterized by impaired bile flow and the accumulation of toxic bile acids in the liver, leading to inflammation and progressive destruction of the bile ducts within the liver and causing increased levels of ALP, alanine transaminase (ALT) and gamma-glutamyl transferase (GGT), enzymes found primarily in the liver, as well as total bilirubin. The most common symptoms of PBC are pruritus (chronic itch) and fatigue, which can be debilitating for some people. Progression of PBC is associated with an increased risk of liver-related mortality.

About Seladelpar

Seladelpar 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 seladelpar has anticholestatic, anti-inflammatory, antipruritic, and antifibrotic effects.

Seladelpar 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.

In the U.S., seladelpar, which is marketed as Livdelzi^®, was granted accelerated approval for the treatment of PBC by the U.S. FDA in August 2024. Seladelpar received FDA Breakthrough Therapy Designation, as well as Orphan Drug Designation for the treatment of people living with PBC. Seladelpar was also approved by the UK MHRA in January 2025. Seladelpar has Priority Medicine (PRIME) designation in the EU, which is assigned to optimize the development of novel medicines that target conditions with an unmet medical need for which no treatment options exists or where they can offer a major therapeutic advantage over existing treatments.

As part of the FDA accelerated approval, Gilead has committed to a confirmatory long-term outcomes study called AFFIRM, which has already been initiated in people with compensated cirrhosis. Continued U.S. approval may be contingent upon verification of clinical benefit in confirmatory trial(s).

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 AFFIRM 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 Quarterly Report on Form 10-Q for the quarter ended September 30, 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, 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).