SNP-630-MS, a novel compound, has shown promising results in both preclinical and phase 2 clinical studies for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). Preclinical studies in mice demonstrated that SNP-630 and its active metabolites can effectively mitigate MASH by reducing liver fat accumulation and fibrosis. A subsequent phase 2 clinical trial in MASH patients revealed a significant reduction in serum alanine aminotransferase (ALT) levels, a key indicator of liver damage, after 12 weeks of treatment with SNP-630-MS.
Preclinical Efficacy of SNP-630 and its Metabolites
In vivo studies using a high-fat diet (HFD)-induced MASH mouse model showed that SNP-630 treatment led to a significant reduction in liver triglyceride (TG) and total cholesterol (TCHO) levels. Histopathological analysis of liver tissue sections revealed a decrease in fat accumulation and fibrosis, as evidenced by hematoxylin and eosin (H&E) and Sirius Red staining, respectively. These findings were further supported by Western blot analysis, which demonstrated a reduction in CYP2E1 expression, a key enzyme involved in oxidative stress and liver injury. Real-time PCR analysis also showed decreased expression of genes associated with fibrosis, such as Col1a1, Col3a1, Timp1, and Acta2.
Phase 2 Clinical Trial Results
The phase 2 clinical trial enrolled patients with MASH who met specific inclusion criteria, including elevated ALT levels or a combination of elevated ALT and a body mass index (BMI) of 25 or greater, along with a diagnosis of type 2 diabetes mellitus. The primary outcome measure was the change in serum ALT levels at week 12 compared to baseline. Secondary outcomes included changes in other liver enzymes (AST, Alk-P, γ-GT), serum CK-18 fragment levels, and liver fat content as measured by MRI. The study also assessed the safety and tolerability of SNP-630-MS.
Results from the clinical trial indicated that SNP-630-MS treatment led to a statistically significant reduction in serum ALT levels after 12 weeks. Furthermore, MRI-based measurements showed a reduction in liver fat content, suggesting that SNP-630-MS can effectively target the underlying steatosis associated with MASH. The study also monitored adverse events (AEs) and serious adverse events (SAEs) to assess the safety profile of SNP-630-MS. The overall safety profile was deemed acceptable, supporting further development of the compound.
Mechanism of Action and Future Directions
While the exact mechanism of action of SNP-630-MS is still under investigation, preclinical data suggest that it may involve modulation of CYP2E1 activity and reduction of oxidative stress. Further studies are needed to fully elucidate the molecular mechanisms underlying its therapeutic effects. These positive findings warrant further investigation of SNP-630-MS in larger, phase 3 clinical trials to confirm its efficacy and safety in a broader MASH patient population. The potential of SNP-630-MS to address the unmet medical need in MASH treatment is significant, offering hope for improved outcomes for patients with this progressive liver disease.
