NorthSea Therapeutics has announced breakthrough results from their Phase 2b ICONA clinical trial evaluating icosabutate for treating metabolic dysfunction-associated steatohepatitis (MASH). The findings, published in the Journal of Hepatology, demonstrate significant improvements in liver fibrosis through multiple analytical methods.
Strong Anti-Fibrotic Effects Demonstrated
The 52-week randomized, double-blind, placebo-controlled trial involved 168 patients with biopsy-confirmed MASH and moderate-to-severe fibrosis. Using AI-assisted digital pathology, 49.2% of patients receiving 600mg icosabutate achieved a ≥1-stage improvement in fibrosis, compared to 25.7% in the placebo group (p=0.02).
Particularly noteworthy results were seen in patients with more advanced disease. Among F3-F4 patients, 32.7% treated with 600mg icosabutate achieved fibrosis improvement without MASH worsening, compared to 9.6% in the placebo group (p=0.004), as assessed by AIM-MASH digital pathology.
Exceptional Response in Diabetic Patients
The drug showed remarkable efficacy in type 2 diabetic patients, with 28.6% and 21.2% of patients on 300mg and 600mg doses respectively achieving fibrosis improvement, while none in the placebo group showed improvement. Additionally, patients experienced improved glycemic control, with approximately 1% placebo-adjusted decrease in HbA1c among diabetic patients with poor baseline control.
Comprehensive Therapeutic Benefits
Beyond fibrosis improvement, icosabutate demonstrated broad therapeutic effects:
- Significant reductions in liver enzymes (ALT, AST, GGT, ALP) and bilirubin
- 20% reduction in PRO-C3 from baseline
- 40% median reduction in hsCRP from baseline
- Improvements in ELF score, indicating reduced fibrosis
Safety Profile and Future Potential
The drug maintained a favorable safety profile, with only mild to moderate treatment-emergent adverse events and no reported cases of drug-induced liver injury. Notably, icosabutate's mechanism of action does not primarily target liver fat reduction, distinguishing it from other MASH therapies.
"The unique mechanism of action, unrelated to a decrease in liver fat, will provide patients with metabolic dysfunction-associated steatotic liver disease, or MASLD, with more options for therapy in the future," stated Dr. Arun Sanyal, Director of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health.
Strategic Positioning for Combination Therapy
Rob de Ree, CEO of NorthSea Therapeutics, emphasized the drug's potential for combination therapy: "We believe there's an important place for a safe, well-tolerated, oral anti-fibrotic with add-on benefits on glycemic control, inflammation and atherogenic lipids in the MASH therapeutic landscape." Pre-clinical studies have already shown synergistic effects when combining icosabutate with GLP-1 receptor agonists for hepatic fibrosis reduction.
The positive results support icosabutate's advancement into further clinical development, particularly focusing on patients with more advanced disease and/or underlying diabetes. The company is positioned to explore both monotherapy and combination therapy approaches in future studies.
