Lenofibrinor
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lanifibranor NASH MASH clinical trial
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Here is a comprehensive overview of Lanifibranor (which "Lenofibrinor" refers to - it is the same drug, IVA337, with "lenofibrinor" being an alternate/variant transliteration used in some regions):
Lanifibranor (IVA337) - Pan-PPAR Agonist
What It Is
Lanifibranor is an oral, small-molecule pan-PPAR agonist developed by Inventiva Pharma (France/USA). It simultaneously activates all three peroxisome proliferator-activated receptor isoforms:
| Isoform | Hepatic Effect |
|---|---|
| PPARα | Increases hepatic fatty acid β-oxidation → reduces steatosis |
| PPARδ | Suppresses macrophage-driven inflammation (inhibits NF-κB, reduces TNF-α, IL-6, IL-1β) |
| PPARγ | Inhibits hepatic stellate cell activation → reduces TGF-β signaling → anti-fibrotic |
This multi-receptor mechanism distinguishes it from selective agents: fibrates target only PPARα, thiazolidinediones only PPARγ. Lanifibranor's pan-PPAR activity gives it coordinated anti-steatotic, anti-inflammatory, and anti-fibrotic effects in a single compound.
Primary Indication
Metabolic dysfunction-associated steatohepatitis (MASH), formerly called NASH - a progressive liver disease with high unmet need, especially in patients with advanced (F2-F3) fibrosis.
Clinical Evidence
Phase IIb - NATIVE Trial (Francque et al., 2021, NEJM)
- 24-week, double-blind RCT in biopsy-confirmed non-cirrhotic NASH
- Primary endpoint met (1200 mg dose): ≥2-point reduction in SAF score (Steatosis-Activity-Fibrosis) with no fibrosis worsening
- Key results at 1200 mg vs placebo:
- NASH resolution without fibrosis worsening: 49% vs 22%
- ≥1-stage fibrosis improvement without NASH worsening: 48% vs 29%
- Safety signals: diarrhea, nausea, peripheral edema, weight gain, anemia
Phase III - NATiV3 Trial (NCT04849728, ongoing)
- 1,009 patients with biopsy-confirmed MASH + significant fibrosis (F2-F3)
- Lanifibranor 1200 mg once daily vs placebo
- Two co-primary histological endpoints (MASH resolution, fibrosis improvement)
- Readout expected in the second half of 2026 - considered one of the most consequential events in the MASH landscape
Position in the MASH Drug Landscape
| Drug | Class | Status (2026) |
|---|---|---|
| Resmetirom (Rezdiffra) | THRβ agonist | FDA-approved (2024) |
| Semaglutide | GLP-1 RA | Phase III (ESSENCE) |
| Lanifibranor | Pan-PPAR agonist | Phase III (NATiV3) |
| Obeticholic acid | FXR agonist | Phase III (REGENERATE) |
A 2026 meta-analysis (PMID 41917519) comparing tirzepatide, lanifibranor, and resmetirom in MASLD, as well as a 2025 network meta-analysis (PMID 39903735) covering multiple MASH pharmacotherapies, both include lanifibranor as an active comparator - reflecting its prominence in the current treatment pipeline.
Key Takeaway
Lanifibranor's pan-PPAR mechanism is mechanistically the broadest among investigational MASH agents. The NATiV3 Phase III readout (H2 2026) will determine whether it becomes the second approved pharmacotherapy for MASH after resmetirom. A positive result would make it particularly valuable in patients where anti-fibrotic effects are prioritized alongside metabolic improvement.
Note: "Lenofibrinor" does not appear as a distinct drug in the medical literature or clinical trial registries - it is a variant spelling/transliteration of lanifibranor (IVA337). If you encountered this name in a specific context (e.g., a regional formulary or translated document), it refers to the same compound.
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