Ursodeoxycholic acid
- Generic Name
- Ursodeoxycholic acid
- Brand Names
- Reltone, Urso, Urso Forte
- Drug Type
- Small Molecule
- Chemical Formula
- C24H40O4
- CAS Number
- 128-13-2
- Unique Ingredient Identifier
- 724L30Y2QR
- Background
Ursodeoxycholic acid (UDCA), also known as ursodiol, is a naturally-occurring bile acid that constitutes a minor fraction of the human bile acid pool. UDCA has been used to treat liver disease for decades: its first use in traditional medicine dates back more than a hundred years. UDCA was first characterized in the bile of the Chinese black bear and is formed by 7b-epimerization of chenodeoxycholic acid, which is a primary bile acid. Due to its hydrophilicity, UDCA is less toxic than cholic acid or chenodeoxycholic acid.
UDCA was first approved by the FDA in 1987 for dissolution of gallstones and for primary biliary cirrhosis in 1996. UDCA works by replacing the hydrophobic or more toxic bile acids from the bile acid pool.
- Indication
Ursodeoxycholic acid is indicated for the treatment of patients with primary biliary cholangitis.
It is used for the short-term treatment of radiolucent, noncalcified gallbladder stones in patients selected for elective cholecystectomy. It is also used to prevent gallstone formation in obese patients experiencing rapid weight loss.
- Associated Conditions
- Gallstones, Primary Biliary Cholangitis
Target RWE Showcases Groundbreaking Liver Disease Research at EASL Congress 2025
• Target RWE presented significant findings on MASH and HCC at EASL Congress 2025, revealing that Type 2 diabetes substantially increases the risk of progression to MASH-related cirrhosis.
• The company's Chief Medical Officer participated in the PBC Consensus Conference, focusing on developing surrogate endpoints and integrating real-world evidence into clinical trials for Primary Biliary Cholangitis.
• With over 600,000 patients enrolled in its TARGET-Liver Disease observational study, Target RWE continues to advance understanding of chronic liver diseases through its partnership with the American Association for the Study of Liver Diseases.
Gilead to Showcase New Data on Liver Disease Treatments at EASL 2025 Congress
• Gilead will present 29 abstracts at the European Association for the Study of the Liver Congress in May 2025, highlighting advancements in treatments for primary biliary cholangitis and viral hepatitis.
• New data will demonstrate Livdelzi's (seladelpar) effectiveness in reducing pruritus in primary biliary cholangitis patients and bulevirtide's potential for maintained virologic response in hepatitis delta virus treatment.
• The company will also present promising results from a Phase 1a study of a novel therapeutic vaccine aimed at achieving functional cure for hepatitis B virus infection.
Ipsen's Elafibranor Shows Promise in Phase II Trial for Primary Sclerosing Cholangitis
• Elafibranor demonstrated a favorable safety profile and significant dose-dependent efficacy in the Phase II ELMWOOD trial for primary sclerosing cholangitis (PSC), a rare liver disease with no currently approved treatments.
• Patients treated with elafibranor showed significant improvements in liver biochemical parameters, including alkaline phosphatase, with stabilization of non-invasive markers of liver fibrosis compared to placebo.
• The 120mg dose of elafibranor significantly improved pruritus symptoms, offering potential relief for a common and distressing symptom experienced by PSC patients.
FDA Grants Accelerated Approval to Ipsen's Iqirvo, First Dual PPAR Agonist for Primary Biliary Cholangitis
• Ipsen's Iqirvo (elafibranor) receives FDA accelerated approval as the first dual PPAR alpha/delta agonist and first new therapy in over a decade for primary biliary cholangitis treatment.
• In the ELATIVE trial, Iqirvo demonstrated significant efficacy with 51% of patients achieving cholestasis response compared to 4% on placebo, marking a substantial therapeutic advancement.
• The drug will be available at $11,500 per month list price, entering a market estimated at $1.5 billion annually for UDCA-refractory PBC treatments.
UK Approves Gilead's Livdelzi (Seladelpar) for Primary Biliary Cholangitis
• The UK's MHRA has approved Gilead's Livdelzi (seladelpar) for adults with primary biliary cholangitis (PBC) who inadequately respond to or cannot tolerate UDCA.
• Livdelzi, a PPAR-delta agonist, reduces bile acid production in the liver, addressing a key factor in PBC progression and symptom management.
• Approval was based on the Phase 3 RESPONSE trial, where Livdelzi significantly improved biochemical response and reduced pruritus compared to placebo.
• This approval provides a new treatment option for approximately 25,000 PBC patients in the UK, offering potential improvements in liver health and quality of life.
Phase 3 Clinical Trial Enrolling to Test Maralixibat for Cholestasis-Related Itch
A Phase 3 clinical trial, EXPAND, is currently enrolling participants to evaluate the effectiveness of maralixibat in treating treatment-resistant itching associated with rare cholestatic conditions. The trial aims to enroll up to 90 participants aged 6 months and older across multiple global sites, with results expected by 2026.
Gilead's Seladelpar Receives European Commission Approval for Primary Biliary Cholangitis
• The European Commission has granted conditional marketing authorization for Gilead's seladelpar for primary biliary cholangitis (PBC).
• Seladelpar is approved for use in combination with UDCA for those with inadequate response, or as a monotherapy for those who cannot tolerate UDCA.
• The approval is based on Phase 3 RESPONSE trial data, showing significant improvements in biochemical response and pruritus reduction.
• This decision provides a new treatment option for PBC patients in Europe, addressing a critical unmet need.
New PPAR Agonists Expand Treatment Landscape for Primary Biliary Cholangitis
• Ursodeoxycholic acid (UDCA), while groundbreaking, leaves up to 40% of Primary Biliary Cholangitis patients with inadequate response, highlighting the need for additional treatment options.
• Recent accelerated approvals of PPAR agonists seladelpar and elafibranor offer new hope, with seladelpar showing the first clinically meaningful improvements in pruritus symptoms.
• Real-world effectiveness and safety profiles of these new treatments remain to be established, as rare but serious side effects typically only emerge with broader clinical use.
Ocaliva's Conditional Approval for PBC Revoked in Europe After Court Ruling
• The European Commission's decision to revoke the conditional marketing authorization for Ocaliva (obeticholic acid) in Europe has been upheld by the General Court of the EU.
• Advanz Pharma, which markets Ocaliva in Europe, had its temporary suspension of the revocation lifted, leading to the drug's immediate withdrawal from the EU and EEA markets.
• The revocation is based on the EMA's reassessment of Ocaliva's benefit-risk profile, concluding it was no more effective than a placebo for primary biliary cholangitis (PBC).
• Ocaliva, a farnesoid X receptor (FXR) agonist, remains available in the US under accelerated approval, while Advanz Pharma considers options for continued patient access in Europe.
Elafibranor Shows No Impact on Renal Function in Primary Biliary Cholangitis Patients
• A secondary analysis of the phase 3 ELATIVE trial indicates that elafibranor treatment does not adversely affect renal function markers in patients with primary biliary cholangitis (PBC).
• The study found that median levels of renal parameters remained stable in both elafibranor and placebo groups over 52 weeks.
• Acute kidney injury was infrequent, with no clinically meaningful changes in renal function observed during the trial.
• Elafibranor received FDA accelerated approval in June 2024 based on its efficacy in reducing alkaline phosphatase levels in PBC patients.
Gilead's Livdelzi Shows Sustained Efficacy and Long-Term Safety in Primary Biliary Cholangitis
• Interim analysis of the Phase 3 ASSURE study reveals that 81% of PBC participants achieved a durable biochemical response with Livdelzi by month 30.
• Notably, 41% of participants experienced normalization of alkaline phosphatase (ALP) levels, a critical marker of liver function, with Livdelzi treatment.
• Livdelzi reduced pruritus severity in PBC participants, leading to near resolution of itch in 27% of those with moderate to severe itch.
• The long-term safety profile of Livdelzi remains robust, with no treatment-related serious adverse events reported throughout the study duration.
Gilead's Livdelzi Shows Sustained Efficacy and Long-Term Safety in Primary Biliary Cholangitis
• Interim analysis of the Phase 3 ASSURE study showed that 81% of participants with PBC achieved a composite biochemical response after two and a half years of Livdelzi treatment.
• 41% of participants achieved normalization of alkaline phosphatase (ALP) levels, a key indicator of liver function, highlighting the drug's potential in managing PBC.
• Livdelzi demonstrated a reduction in pruritus severity, with nearly resolution of itch in 27% of participants with moderate to severe itch, improving quality of life.
• Long-term safety data indicated that Livdelzi was generally well-tolerated, with no treatment-related serious adverse events reported, supporting its use as a durable treatment option.
FDA Flags Liver Injury Risk with Obeticholic Acid (Ocaliva) in Non-Cirrhotic PBC Patients
• The FDA has identified a risk of serious liver injury in primary biliary cholangitis (PBC) patients without cirrhosis taking obeticholic acid (Ocaliva).
• Postmarketing data revealed a higher risk of liver transplant or death in patients on obeticholic acid compared to placebo, prompting a safety alert.
• The FDA advises frequent liver test monitoring for patients on obeticholic acid and discontinuation if liver disease progression or lack of efficacy is observed.
• Clinicians are urged to educate patients about liver damage symptoms and the importance of seeking prompt medical attention.
FDA Rejects Full Approval of Obeticholic Acid for Primary Biliary Cholangitis
• The FDA declined to grant full approval to obeticholic acid (Ocaliva) for treating primary biliary cholangitis (PBC), citing concerns over its benefit-risk profile.
• The decision follows a negative recommendation from the agency's advisory committee, which questioned the drug's clinical benefit as a second-line agent.
• Intercept Pharmaceuticals plans to collaborate with the FDA on next steps, while the drug remains available on the market despite safety concerns.
• The FDA has granted accelerated approval to two other drugs, seladelpar (Livdelzi) and elafibranor (Iqirvo), for PBC treatment this year.
FDA Denies Full Approval for Ocaliva in Primary Biliary Cholangitis Treatment
• The FDA issued a Complete Response Letter (CRL) to Intercept Pharmaceuticals' Ocaliva (obeticholic acid) for primary biliary cholangitis (PBC).
• The decision aligns with a negative opinion from the Gastrointestinal Drugs Advisory Committee regarding Ocaliva's benefit-risk profile.
• Ocaliva remains available in the US under accelerated approval, despite the recent approvals of Iqirvo (elafibranor) and Livdelzi (seladelpar).
• Intercept Pharmaceuticals intends to collaborate with the FDA to determine the next steps for Ocaliva's full approval in treating PBC.
FDA Delays Decision on Ocaliva's Full Approval for Primary Biliary Cholangitis
• The FDA has extended its review of Intercept Pharmaceuticals' Ocaliva (obeticholic acid) for full approval in primary biliary cholangitis (PBC).
• The decision was initially expected by October 15, 2024, but the FDA has not provided a new anticipated action date.
• Ocaliva remains available in the U.S. under accelerated approval for PBC patients who have inadequate response or cannot tolerate UDCA.
• The delay follows a negative opinion from an FDA advisory committee regarding Ocaliva's clinical benefit and risk-benefit profile.
FDA's Accelerated Drug Approvals Face Scrutiny Over Efficacy and Cost
• The FDA's accelerated approval pathway, designed to expedite access to promising treatments, is facing increased scrutiny due to concerns over the efficacy and cost of some approved drugs.
• Ocaliva, approved for primary biliary cholangitis, exemplifies the debate, as it lowers enzyme levels but lacks definitive proof of long-term clinical benefits, costing approximately $100,000 annually.
• Critics argue that the reliance on surrogate markers and the influence of user fees paid by pharmaceutical companies may lead to the approval of marginally effective and expensive drugs.
• While the accelerated approval process has sped up drug availability, particularly for diseases like HIV, there are calls for stricter requirements for confirmatory trials to ensure lasting value and patient benefit.
PBC Treatment Landscape Evolves with New Drug Approvals and Regulatory Scrutiny
• The FDA approved Iqirvo (elafibranor, Ipsen/Genfit) as a second-line treatment for primary biliary cholangitis (PBC) in patients with inadequate response or intolerance to UDCA.
• Livdelzi (seladelpar, Gilead) also received accelerated FDA approval for PBC, offering another option for patients who do not respond to or cannot tolerate UDCA.
• An FDA advisory committee voted against the full approval of Ocaliva (obeticholic acid), raising concerns about its long-term safety and efficacy data.
• These developments mark a significant shift in the PBC treatment paradigm, introducing new therapeutic options and challenging the existing market landscape.
CNP-104 Shows Promise in Phase 2a Trial for Primary Biliary Cholangitis
• CNP-104 demonstrated a statistically significant decrease in liver stiffness compared to placebo in patients with primary biliary cholangitis (PBC).
• The investigational therapy also showed favorable changes in pathogenic CD4 T cell populations and tolerance-inducing CD8 T cells.
• CNP-104 was safe and well-tolerated, with all drug-related adverse events reported as mild during the 120-day primary study period.
• These results suggest CNP-104 has the potential to halt disease progression, offering a transformational advancement for PBC treatment.
Ipsen's Iqirvo Receives European Approval for Primary Biliary Cholangitis
• The European Commission has granted conditional approval to Ipsen's Iqirvo (elafibranor) for treating primary biliary cholangitis (PBC) in adults.
• Iqirvo is approved for use with ursodeoxycholic acid (UDCA) in patients with inadequate response or as a monotherapy for those who cannot tolerate UDCA.
• The approval is based on the Phase III ELATIVE trial, which showed significant treatment benefits compared to placebo in reducing liver damage markers.
• Iqirvo is the first new therapy approved for PBC in the EU in nearly a decade, offering a new treatment choice for patients.
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