Elafibranor
- Generic Name
- Elafibranor
- Brand Names
- Iqirvo
- Drug Type
- Small Molecule
- Chemical Formula
- C22H24O4S
- CAS Number
- 923978-27-2
- Unique Ingredient Identifier
- 2J3H5C81A5
- Background
Elafibranor (code name GFT505) is a multimodal and pluripotent medication for treatment of atherogenic dyslipidemia for an overweight patient with or without diabetes. It is an oral treatment that acts on the 3 sub-types of PPAR (PPARa, PPARg, PPARd) with a preferential action on PPARa. As of February 2016, elafibranor has completed 8 clinical trials and a phase III is in progress.
- Indication
Investigated for use/treatment in atherosclerosis and diabetes mellitus type 2.
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.
Ipsen Secures €500 Million Inaugural Rated Public Bond Following Investment Grade Ratings
• Ipsen has successfully completed its first Rated Public Bond of €500 million with a 3.875% coupon maturing in March 2032, following Investment Grade ratings from S&P (BBB-) and Moody's (Baa3).
• The transaction was heavily oversubscribed by institutional investors, demonstrating market confidence in Ipsen's financial strategy and long-term growth prospects.
• This bond issuance is part of Ipsen's broader refinancing plan, which recently included the renewal of a €1.5 billion Revolving Credit Facility, significantly extending the company's debt maturity profile.
Ipsen Advances Pipeline with Multiple Regulatory Wins and Strategic Partnerships in 2024
• Ipsen secured FDA approval for Onivyde in first-line pancreatic cancer treatment and gained approvals for Iqirvo and Kayfanda in the U.S. and EU markets, expanding their therapeutic portfolio.
• The company strengthened its pipeline through strategic partnerships, including agreements with Sutro Biopharma, Foreseen Biotechnology, and DayOne Biopharmaceuticals for innovative oncology assets.
• Looking ahead to 2025, Ipsen projects sales growth exceeding 5.0% and anticipates key regulatory decisions for Cabometyx in neuroendocrine tumors and tovorafenib in pediatric low-grade glioma.
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.
FDA Leads Global Drug Approvals in 2024 with 50 Novel Medicines, Outpacing EMA's 46
• The FDA approved 50 novel drugs in 2024, slightly down from 55 in 2023, while the EMA increased its approvals to 46 from 39 in the previous year.
• Over half of FDA's novel drug approvals targeted rare diseases affecting fewer than 200,000 people, with 68% of approvals occurring first in the US before other countries.
• Both agencies approved significant breakthrough treatments, including Hympavzi for hemophilia, needle-free anaphylaxis spray Neffy/Eurneffy, and new therapies for primary biliary cholangitis.
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.
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.
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.
Iqirvo (Elafibranor) Shows Sustained Efficacy and Safety in Long-Term PBC Treatment
• Interim data from the open-label extension of the Phase III ELATIVE trial demonstrate Iqirvo's sustained efficacy and safety profile for up to three years in patients with primary biliary cholangitis (PBC).
• Patients treated with Iqirvo experienced improvements in pruritus and stabilization of surrogate markers of liver fibrosis, suggesting a positive impact on disease progression.
• Exploratory endpoints revealed that Iqirvo led to improvements in fatigue and sleep, as reported by patients, highlighting its potential to address key symptoms of PBC.
• The safety profile of Iqirvo remained consistent with previous findings, with no new safety concerns identified during the extended treatment period.
Ipsen's Iqirvo (elafibranor) Shows Sustained Efficacy and Safety in Long-Term PBC Treatment
• Interim analysis of the Phase III ELATIVE study's open-label extension shows Iqirvo (elafibranor) maintains efficacy and safety for up to three years in PBC patients.
• Patients treated with Iqirvo experienced sustained improvements in pruritus and stabilization of surrogate markers of liver fibrosis over the three-year period.
• Exploratory endpoints revealed improvements in fatigue and sleep, as reported by patients, highlighting the potential for enhanced quality of life.
• The ongoing confirmatory study (NCT06016842) aims to further verify the clinical benefits of Iqirvo in treating primary biliary cholangitis.
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.
Cell Therapy and Targeted Therapies Dominate Oncology Advances in Early 2025
• The FDA issued a CRL for Atara Biotherapeutics' tabelecleucel due to third-party manufacturing issues, not efficacy or safety data, delaying potential approval for EBV+ PTLD.
• EsoBiotec dosed the first patient in a trial for ESO-T01, an in vivo BCMA-directed CAR-T therapy for multiple myeloma, aiming for lower costs and simplified administration.
• Obecabtagene autoleucel (obe-cel) gained FDA approval for relapsed/refractory B-cell precursor ALL, offering a less toxic CD19-directed CAR T-cell therapy option.
• Arlocabtagene autoleucel (arlo-cel) shows promise in heavily pretreated relapsed/refractory multiple myeloma, eliciting a 48% complete response rate in phase 1 studies.
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.
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.
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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