Obeticholic acid
- Generic Name
- Obeticholic acid
- Brand Names
- Ocaliva
- Drug Type
- Small Molecule
- Chemical Formula
- C26H44O4
- CAS Number
- 459789-99-2
- Unique Ingredient Identifier
- 0462Z4S4OZ
- Background
Primary biliary cirrhosis, or PBC, is a progressive and chronic condition that leads to hepatic injury often resulting in end-stage liver failure that requires liver transplantation.
Obeticholic acid is a farnesoid-X receptor (FXR) agonist used to treat this condition, possibly allowing for increased survival. In 2016, it was granted approval to treat primary biliary cholangitis in combination with ursodeoxycholic acid, which was previously the mainstay treatment for this condition. In May 2021, the FDA updated its prescribing information to contraindicate the use of obeticholic acid in patients with PBC and advanced cirrhosis (e.g. those with portal hypertension or hepatic decompensation) due to a risk of liver failure, in some cases requiring liver transplantation.
Obeticholic acid is currently being considered for FDA approval to treat fibrosis caused by non-alcoholic liver steatohepatitis (NASH). The NDA from Intercept Pharmaceuticals was approved in November 2019 and obeticholic acid is expected to be granted full approval for this indication in 2020.
- Indication
用于治疗原发性胆汁性胆管炎(PBC)或用于治疗原发性胆汁性肝硬化（PBC）。
- Associated Conditions
- Primary Biliary Cholangitis
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.
FDA Grants Breakthrough Therapy Status to Radiprodil for GRIN-Related Seizure Treatment
• GRIN Therapeutics' radiprodil receives FDA Breakthrough Therapy designation for treating seizures in patients with GRIN-related neurodevelopmental disorder, showing 86% median reduction in seizure frequency during Phase 1b trials.
• The investigational drug demonstrated significant efficacy in Phase 1b Honeycomb study, with 71% of patients achieving over 50% reduction in countable motor seizures and most patients showing behavioral improvements.
• The company plans to initiate Phase 3 pivotal trials in mid-2025, backed by a $200M capital commitment from Blackstone Life Sciences, to evaluate radiprodil's impact on seizures and behavioral outcomes.
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.
COUR Pharmaceuticals' CNP-104 Receives FDA Orphan Drug Designation for Primary Biliary Cholangitis
• COUR Pharmaceuticals' CNP-104, a novel therapy for primary biliary cholangitis (PBC), has been granted Orphan Drug Designation by the FDA.
• The designation follows positive Phase 2a trial data, which demonstrated favorable T cell responses and slowed disease progression in PBC patients.
• CNP-104 aims to address the root cause of PBC by inducing tolerance to pathogenic activated PDC-E2 T-cells, potentially modifying the disease course.
• The FDA's decision provides incentives for CNP-104's development, including tax credits, waived fees, and potential market exclusivity upon approval.
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.
FDA Wraps Up 2024 with Key Approvals for Drugs Targeting Various Conditions
• The FDA approved Vertex's Alyftrek for cystic fibrosis, offering improved dosing and potential market exclusivity.
• Novo Nordisk's Alhemo was approved for hemophilia A and B, providing a new option for patients with inhibitors.
• Bristol Myers Squibb's Opdivo Qvantig gained approval as a subcutaneous formulation, offering faster administration for various solid tumors.
• Eli Lilly's Zepbound secured approval for obstructive sleep apnea in obese adults, marking the first prescription medicine for this condition.
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.
Outlook Therapeutics Faces Setback in AMD Trial; Other R&D Updates
• Outlook Therapeutics' ONS-5010 failed to meet the noninferiority endpoint in a Phase III wet AMD trial, impacting company shares but BLA resubmission is still planned for early 2025.
• The EMA revoked conditional marketing approval for Advanz Pharma's Ocaliva for primary biliary cholangitis (PBC) after a legal challenge failed.
• Arovella Therapeutics is advancing ALA-101, a CAR-19-iNKT cell therapy, towards clinical trials for blood cancers and solid tumors, showing enhanced efficacy in preclinical studies.
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.
GSK's Linerixibat Shows Positive Phase III Results for Cholestatic Pruritus in Primary Biliary Cholangitis
• GSK's linerixibat met its primary endpoint in the GLISTEN Phase III trial, demonstrating a statistically significant reduction in itch for PBC patients with moderate to severe pruritus.
• The trial evaluated linerixibat in PBC patients already receiving guideline-suggested therapies, treatment-naïve patients, and previously treated patients, showing potential as a targeted therapy.
• Linerixibat, an ileal bile acid transporter (IBAT) inhibitor, could be the first global therapy specifically developed to treat itch in PBC, addressing a significant unmet need.
• Preliminary safety results were consistent with prior studies, and full results from the GLISTEN trial will be presented at a future scientific congress.
Elafibranor Demonstrates Improved Transplant-Free Survival in PBC Patients
• Elafibranor (Iqirvo) shows early improvements in predicted transplant-free survival for primary biliary cholangitis (PBC) patients based on GLOBE and UK-PBC scores.
• The Phase 3 ELATIVE study data presented at The Liver Meeting 2024 indicates improvements as early as week 4, sustained through 52 weeks of treatment.
• The improvements are primarily driven by reductions in alkaline phosphatase (ALP) levels, a key marker in PBC prognosis.
• Elafibranor received accelerated FDA approval in June 2024 for second-line treatment of PBC, supported by ALP reduction in the ELATIVE trial.
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 Ocaliva for Second-Line PBC Treatment
• The FDA has denied full approval for Intercept Pharmaceuticals' Ocaliva (obeticholic acid) as a second-line treatment for primary biliary cholangitis (PBC) due to safety concerns.
• The decision aligns with an FDA advisory committee's negative vote, citing insufficient evidence of clinical benefit and a favorable risk-benefit profile for Ocaliva.
• Ocaliva remains available in the U.S. under conditional approval for PBC patients who have not responded adequately to ursodeoxycholic acid.
• Conditional approval in the EU was recently revoked, but is temporarily suspended, and Ocaliva is still available, pending further review.
FDA Rejects Full Approval for Intercept's Ocaliva in Primary Biliary Cholangitis
• The FDA issued a complete response letter for Intercept's Ocaliva, preventing its full approval for primary biliary cholangitis (PBC).
• The decision aligns with a negative opinion from the Gastrointestinal Drugs Advisory Committee (GIDAC) regarding Ocaliva's clinical benefit.
• Ocaliva will remain available in the US under its existing accelerated approval, while the FDA considers post-marketing study data.
• This setback follows previous regulatory challenges for Ocaliva, including rejection for NASH and withdrawal of European conditional approval.
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
• The FDA issued a complete response letter to Intercept Pharmaceuticals, denying full approval for Ocaliva (obeticholic acid) for primary biliary cholangitis (PBC).
• The decision aligns with an earlier advisory panel vote citing concerns about verifying Ocaliva's benefits on clinical outcomes in PBC patients without cirrhosis.
• The FDA will continue to evaluate safety data from Intercept's postmarketing confirmatory trial to assess potential benefits not seen in other therapies.
• Ocaliva remains available under accelerated approval as a second-line treatment for PBC patients inadequately responding to or intolerant of ursodeoxycholic acid.
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 Weighs Removal of Oral Phenylephrine; Approves Drugs for CML, Gastric Cancer, and UTIs
• The FDA is considering removing oral phenylephrine from its OTC Monograph due to a lack of efficacy as a nasal decongestant, potentially impacting numerous cold and allergy products.
• Novartis' Scemblix expands its FDA-approved uses to include the treatment of newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ PML).
• Astellas Pharma's Vyloy (zolbetuximab) receives FDA approval as the first treatment targeting the CLDN18.2 protein for gastric or gastroesophageal junction adenocarcinoma.
• Iterum Therapeutics' Orlynvah (sulopenem) gains FDA approval for treating uncomplicated urinary tract infections in women with limited oral antibacterial treatment options.
Regulatory Setbacks for PTC's Translarna, Eisai/Biogen's Leqembi; Novartis Licenses Cancer Drug from Chengdu Baiyu
• The EMA has reaffirmed its decision not to renew the marketing permit for PTC Therapeutics' Translarna for Duchenne muscular dystrophy due to insufficient evidence of effectiveness.
• Novartis has acquired global licensing rights to a small molecule cancer drug from Chengdu Baiyu Pharmaceutical for $70 million upfront, potentially reaching $1.1 billion with milestones.
• Australia's Therapeutic Goods Administration declined to approve Eisai and Biogen's Leqembi for Alzheimer's disease, citing safety risks outweighing benefits.
FDA Delays Decisions on Amgen's Lumakras and Intercept's Ocaliva
• The FDA has postponed the decision dates for Amgen's Lumakras supplemental application for metastatic colorectal cancer due to disappointing survival data.
• Intercept Pharmaceuticals' Ocaliva's full approval for primary biliary cholangitis (PBC) also faces delay, pending further FDA review of its supplemental New Drug Application.
• Ocaliva's application was previously met with skepticism from the FDA's Gastrointestinal Drug Advisory Committee, citing concerns over efficacy and safety data.
• Both Lumakras and Ocaliva initially received accelerated approval but now face challenges in securing full approval due to mixed confirmatory data.
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