Organovo Holdings, Inc. (Nasdaq:ONVO) announced the presentation of clinical data from its Phase 2 trial of FXR314 in patients with Metabolic Dysfunction-Associated Steatohepatitis (MASH) at The Liver Meeting, sponsored by the American Association for the Study of Liver Diseases (AASLD). The data, presented by Dr. Eric Lawitz, highlighted the efficacy and safety of FXR314 in reducing liver fat content in MASH patients.
The Phase 2 study was a 16-week, randomized, placebo-controlled, multi-center trial involving 214 patients with MASH. Participants were randomized in a 1:1:1 ratio to receive either 3 mg or 6 mg of FXR314, or placebo. The primary endpoint was the change in liver fat content from baseline, as measured by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF).
Key Findings
Results from the study demonstrated a statistically significant reduction in liver fat content from baseline in patients receiving FXR314 compared to placebo. Specifically, the least squares (LS) mean percent reduction in liver fat content at the end of treatment was 22.8% (p=0.0010) with the 3 mg dose and 17.5% (p=0.0267) with the 6 mg dose, compared to 6.1% in the placebo group.
Furthermore, a significant proportion of subjects treated with FXR314 achieved a >30% reduction in MRI-PDFF, with 29.2% (p=0.0023) in the 3 mg group and 32.2% (p=0.0020) in the 6 mg group, compared to 9.5% in the placebo group. Investigators also observed improvements in hepatocellular damage and liver function based on serological measures, with no evidence of worsening of liver fibrosis.
Safety and Tolerability
FXR314 was found to be safe and well-tolerated in the study. Treatment-emergent adverse events were mostly mild to moderate in severity, with incidence comparable between the FXR314 and placebo groups. Drug-related treatment discontinuation was low in frequency and similar across all groups. Notably, FXR314 did not demonstrate significant adverse events typical of the FXR class, including pruritus (3 mg 2.8%, 6 mg 4.2% and placebo 2.8%) and LDL-C level increases (change from baseline of 1.5%, 4.5% and -3.6% for 3mg, 6mg, and placebo groups respectively).
Expert Commentary
Dr. Lawitz commented on the results, stating, "These results are encouraging as we saw FXR314 treatment resulting in liver fat reduction but did not demonstrate the expected toxicities of this class. Due to this unique profile, I am excited about the prospects of further evaluating FXR314 for the treatment of MASH. The intestinal activating specificity is intriguing."
About FXR314
FXR314 is Organovo's lead clinical stage drug, currently under Phase 2 investigation for inflammatory bowel disease, with potential applications in metabolic liver disease and oncology. It is a novel non-bile acid FXR agonist designed with intestinal activating specificity.
