Gilead’s Livdelzi (Seladelpar) Granted Accelerated Approval for Primary Biliary Cholangitis by U.S. FDA
Gilead Sciences has received accelerated FDA approval for Livdelzi (seladelpar) to treat primary biliary cholangitis (PBC) in adults. The approval is based on the Phase 3 RESPONSE study, where 62% of Livdelzi patients achieved the primary endpoint versus 20% on placebo. Livdelzi demonstrated significant reductions in alkaline phosphatase (ALP) levels and pruritus (itching), key markers of PBC progression. As the first and only treatment to show statistically significant improvements in both pruritus and cholestasis markers, Livdelzi challenges the current PBC standard of care. The drug's continued approval may depend on confirmatory trials demonstrating clinical benefits in survival or prevention of liver decompensation.
Gilead Sciences ha ricevuto l'approvazione accelerata dalla FDA per Livdelzi (seladelpar) per trattare la colangite biliare primaria (PBC) negli adulti. L'approvazione si basa sullo studio fase 3 RESPONSE, dove il 62% dei pazienti trattati con Livdelzi ha raggiunto l'obiettivo primario rispetto al 20% con placebo. Livdelzi ha dimostrato significative riduzioni nei livelli di fosfatasi alcalina (ALP) e nel prurito, marcatori chiave della progressione della PBC. Essendo il primo e unico trattamento a mostrare miglioramenti statisticamente significativi sia nel prurito che nei marcatori di colestasi, Livdelzi sfida gli attuali standard di cura per la PBC. L'approvazione continua del farmaco potrebbe dipendere da studi di conferma che dimostrino benefici clinici in termini di sopravvivenza o prevenzione della decompensazione epatica.
Gilead Sciences ha recibido la aprobación acelerada de la FDA para Livdelzi (seladelpar) para tratar la colangitis biliar primaria (PBC) en adultos. La aprobación se basa en el estudio de fase 3 RESPONSE, donde el 62% de los pacientes con Livdelzi alcanzaron el objetivo primario frente al 20% en placebo. Livdelzi mostró reducciones significativas en los niveles de fosfatasa alcalina (ALP) y en el prurito, marcadores clave de la progresión de la PBC. Siendo el primer y único tratamiento que ha demostrado mejoras estadísticamente significativas tanto en prurito como en marcadores de colestasis, Livdelzi desafía el estándar actual de atención para la PBC. La continuación de la aprobación del fármaco puede depender de estudios de confirmación que demuestren beneficios clínicos en la supervivencia o en la prevención de la descompensación hepática.
길리어드 사이언스(Gilead Sciences)는 리브델지(Livdelzi, 셀라델파르)에 대해 성인의 원발성 담관염(PBC) 치료를 위한 FDA의 가속 승인을 받았습니다. 이 승인은 3상 RESPONSE 연구를 기반으로 하며, 리브델지 환자의 62%가 플라시보 그룹의 20%에 비해 주요 목표를 달성했습니다. 리브델지는 알칼리성 포스파타제(ALP) 수치와 가려움증(가려움증)에서 유의미한 감소를 보였으며, 이는 PBC 진행의 주요 지표입니다. 리브델지는 가려움증과 담즙 정체 마커 모두에서 통계적으로 유의미한 개선을 보여준 첫 번째이자 유일한 치료제로서 기존의 PBC 치료 기준에 도전합니다. 이 약물의 지속적인 승인은 생존에 대한 임상적 이점이나 간 부전 예방을 입증하는 확인 시험에 따라 달라질 수 있습니다.
Gilead Sciences a reçu l'approbation accélérée de la FDA pour Livdelzi (seladelpar) afin de traiter la cholangite biliaire primaire (PBC) chez les adultes. Cette approbation est basée sur l'étude clinique de phase 3 RESPONSE, où 62 % des patients ayant reçu Livdelzi ont atteint l'objectif principal contre 20 % dans le groupe placebo. Livdelzi a montré des réductions significatives des niveaux de phosphatase alcaline (ALP) et du prurit (démangeaisons), qui sont des indicateurs clés de la progression de la PBC. Étant le premier et unique traitement à montrer des améliorations statistiquement significatives à la fois dans le prurit et les marqueurs de cholestase, Livdelzi remet en question les normes actuelles de traitement de la PBC. L'approbation continue du médicament pourrait dépendre d'essais de confirmation démontrant des bénéfices cliniques en termes de survie ou de prévention de la décompensation hépatique.
Gilead Sciences hat eine beschleunigte Genehmigung der FDA für Livdelzi (Seladelpar) zur Behandlung von primärer biliärer Cholangitis (PBC) bei Erwachsenen erhalten. Die Genehmigung basiert auf der Phase-3-Studie RESPONSE, in der 62% der Livdelzi-Patienten das primäre Ziel im Vergleich zu 20% in der Placebogruppe erreicht haben. Livdelzi zeigte signifikante Reduktionen der alkalischen Phosphatase (ALP)-Werte und des Pruritus (Juckreiz), wichtige Marker für die Progression der PBC. Als erste und einzige Behandlung, die statistisch signifikante Verbesserungen sowohl bei Pruritus als auch bei Cholestase-Markern zeigte, stellt Livdelzi den aktuellen Standard der PBC-Behandlung in Frage. Die fortlaufende Genehmigung des Arzneimittels könnte von Bestätigungsstudien abhängen, die klinische Vorteile in Bezug auf Überleben oder Prävention von Leberdekompensation belegen.
- Accelerated FDA approval for Livdelzi to treat primary biliary cholangitis
- 62% of patients achieved primary endpoint in Phase 3 RESPONSE study vs 20% on placebo
- 25% of patients achieved ALP normalization at month 12 vs 0% on placebo
- Statistically significant reduction in pruritus compared to placebo
- First treatment to show significant improvements in both pruritus and cholestasis markers
- Potential to challenge current PBC standard of care
- Continued approval contingent on confirmatory trials showing clinical benefit
- No demonstrated improvement in survival or prevention of liver decompensation events
- Not recommended for patients with decompensated cirrhosis
- Potential side effects include headache, abdominal pain, nausea, and dizziness
- Risk of fractures reported in 4% of Livdelzi-treated patients
Insights
The FDA's accelerated approval of Livdelzi represents a significant milestone for Gilead Sciences. This new treatment for primary biliary cholangitis (PBC) has the potential to expand Gilead's market share in the liver disease segment. The approval is based on promising clinical data, showing 62% of participants achieving the primary endpoint compared to 20% on placebo.
From a financial perspective, this approval could positively impact Gilead's revenue stream. With approximately 130,000 Americans affected by PBC, Livdelzi has a substantial potential market. However, investors should note that continued approval is contingent on confirmatory trials, which adds an element of risk.
The competitive advantage of Livdelzi lies in its unique profile, being the only treatment to show significant improvements in both pruritus and disease progression markers. This could lead to strong market adoption and potentially higher pricing power, positively affecting Gilead's profit margins in the long term.
Livdelzi's approval marks a significant advancement in PBC treatment. The drug's mechanism as a PPAR-delta agonist offers a novel approach to managing this chronic liver disease. The RESPONSE study results are impressive, with 25% of patients achieving ALP normalization, a key predictor of liver transplant risk and mortality.
The drug's dual action on both biochemical markers and pruritus is particularly noteworthy. This addresses not only disease progression but also quality of life issues, which could lead to improved patient compliance and outcomes. However, it's important to note that long-term clinical benefits, such as improved survival or prevention of liver decompensation, are yet to be demonstrated.
The ongoing AFFIRM study will be critical in confirming Livdelzi's long-term efficacy and safety, especially in patients with compensated cirrhosis. This data will be essential for maintaining FDA approval and potentially expanding the drug's indications in the future.
Livdelzi's approval positions Gilead to potentially disrupt the current PBC treatment landscape. The drug's unique profile, addressing both disease progression and quality of life issues, could lead to rapid market penetration. With the PBC patient population growing and current treatments falling short for many, Livdelzi could quickly become a preferred option for both physicians and patients.
Gilead's established presence in liver disease therapies gives them a strong foundation for Livdelzi's launch. Their existing relationships with hepatologists and gastroenterologists could accelerate adoption. The company's commitment to patient support programs and continued funding for PBC organizations may also enhance brand loyalty and patient access.
The global potential for Livdelzi is significant, with regulatory reviews underway in the UK and EU. This international expansion could substantially increase the drug's market reach and revenue potential. However, investors should monitor the outcomes of confirmatory trials, as they will be important for long-term market sustainability.
– First and Only Treatment to Demonstrate Statistically Significant Reductions Across Key Biomarkers, ALP Normalization and Pruritus Versus Placebo –
– Livdelzi Expands Gilead’s Long-Standing Commitment to People Living with Liver Disease –
Livdelzi (Photo: Business Wire)
The accelerated approval was based primarily on data from the pivotal placebo-controlled Phase 3 RESPONSE study. In the study,
The FDA approved Livdelzi under accelerated approval based on a reduction of ALP. Improvement in survival or prevention of liver decompensation events have not been demonstrated. Continued approval of Livdelzi for the approved indication may be contingent on verification and description of clinical benefit in confirmatory trial(s).
“More people are being diagnosed with PBC, impacting people of varied ages, gender, race and ethnicity. Those living with PBC share common symptoms, including incessant itching or skin-crawling sensations, as well as debilitating fatigue that is made worse by the itching at night,” said Carol Roberts, President, The PBCers Organization. “The availability of a new treatment option that can help reduce this intense itching while also improving biomarkers of active liver disease is a milestone for our community.”
PBC is a rare, chronic, autoimmune disease of the bile ducts that affects approximately 130,000 Americans, primarily women, and can cause liver damage and possible liver failure if untreated. The disease currently has no cure.
Livdelzi, an oral, peroxisome proliferator activated receptor (PPAR) delta agonist, or delpar, is positioned to challenge the current PBC standard of care, which falls short for many people who experience inadequate response to treatment, putting them at risk for continued liver damage. Livdelzi has demonstrated a sustained efficacy and safety profile across its robust development program to date, including a capacity to normalize ALP levels for some of the people studied with PBC. Given ALP levels are recognized as an important surrogate marker of disease progression in PBC, providers are shifting to view ALP normalization as a treatment goal.
“People living with PBC have been waiting for treatment advancements for many years. Today’s approval of Livdelzi, with its distinct profile, provides them with an important new option,” said Daniel O’Day, Chairman and Chief Executive Officer, Gilead Sciences. “We look forward to leveraging Gilead’s long-standing expertise in liver disease to bring this promising new treatment to all those who could benefit.”
The RESPONSE study, in addition to other studies including the long-term open-label ASSURE study and prior earlier phase studies, together represent the experience with Livdelzi in more than 500 participants with PBC. Ongoing studies include the confirmatory Phase 3 AFFIRM study, a randomized, placebo-controlled confirmatory study designed to evaluate the effect of Livdelzi on clinical outcomes in people with compensated cirrhosis due to PBC.
In the RESPONSE study, Livdelzi, given alone or in combination with UDCA as an oral, once-daily medicine, reduced key biomarkers of PBC disease and helped reduce pruritus (chronic itch), which is a common symptom that can significantly impair quality of life in people with PBC. Livdelzi is the only medicine to demonstrate statistically significant and durable improvements in both pruritus and markers of cholestasis related to the risk of disease progression in a Phase 3 trial. The primary endpoint of the study was a composite biochemical response at month 12, where biochemical response was defined as achieving ALP less than 1.67-times upper limit of normal (ULN), an ALP decrease of greater than or equal to
Commitment to Advocacy, Access and Global Reach
The Gilead Support Path® Program offers information and resources to help patients who are prescribed Livdelzi understand coverage and financial options.
Following the acquisition of CymaBay, Gilead will continue to provide funding to PBC patient organizations.
Livdelzi received FDA Breakthrough Therapy Designation, as well as Orphan Drug Designation for the treatment of people living with PBC.
Seladelpar has also been accepted for review by the
Please see below for
About Livdelzi
Livdelzi (seladelpar) is an oral PPAR-delta agonist, or delpar, for the treatment of primary biliary cholangitis (PBC). PPAR-delta has been shown to regulate critical metabolic and liver disease pathways. Preclinical and clinical data support its ability to regulate genes involved in bile acid synthesis, inflammation, lipid metabolism and transport and fibrosis.
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 reduction across biochemical response, alkaline phosphatase (ALP) normalization, and pruritus versus placebo. Pruritus is a common symptom that can significantly impair quality of life in people with PBC.
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 approval may be contingent upon verification of clinical benefit in confirmatory trial(s).
Livdelzi is indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have 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).
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 PBC
PBC is a rare, chronic inflammatory liver disease primarily affecting women (1 in 1,000 women over the age of 40 or about 130,000 total people in the
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 people living with hepatitis B or D, our focus on advancing our medicines drives hope that today’s research will turn into tomorrow’s cures. Beyond viral hepatitis, we’re working to deliver advanced treatments for people living with PBC. But our commitment doesn’t stop there. Through our ground-breaking science and collaborative partnerships, we strive to create healthier futures for everyone living with liver disease. We are 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. Gilead operates in more than 35 countries worldwide, with headquarters in
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 RESPONSE, ENHANCE, ASSURE and any confirmatory studies); uncertainties relating to regulatory applications and related filing and approval timelines, including MHRA and EMA reviews of seladelpar for the treatment of PBC; 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; the risk that physicians may not see the benefits of prescribing Livdelzi 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 June 30, 2024, as filed with the
Livdelzi, Support Path, Gilead and the Gilead logo are registered trademarks of Gilead Sciences, Inc., or its related companies.
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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Meaghan Smith, Media
public_affairs@gilead.com
Jacquie Ross, Investors
investor_relations@gilead.com
Source: Gilead Sciences, Inc.
FAQ
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