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ION224 From Ionis Lowers Liver Inflammation and Fat in Phase IIb MASH Study

Phase III trials are needed to confirm benefit for potential regulatory review.

Overview

  • The Lancet-published Phase IIb trial enrolled 160 adults with biopsy-confirmed MASH across 43 sites in the United States and Puerto Rico.
  • Monthly subcutaneous dosing up to 120 mg produced improvement in nearly 60% of patients at the highest dose versus 19% on placebo, without worsening fibrosis.
  • ION224 inhibits the liver enzyme DGAT2, directly targeting hepatic fat production and storage as a mechanistically distinct approach.
  • Investigators reported frequent adverse events in both arms but no deaths or treatment-related serious adverse events, indicating acceptable tolerability.
  • Efficacy occurred independent of weight change, supporting potential combination with GLP-1–based weight-loss therapies as the field evolves after resmetirom’s 2024 approval.