AXA1125 safe, well tolerated up to 16 weeks in patients with NAFLD
Among patients with nonalcoholic fatty liver disease, AXA1125 showed greater activity over 16 weeks compared with AXA1957 and placebo, according to a study published in The American Journal of Gastroenterology.
“[Our] systematic characterization of specific [endogenous metabolic modulator (EMM)] compositions in NAFLD adds to the depth of knowledge on the safety and physiologic activity of EMMs and highlights that specificity of EMM composition matters for optimal effects,” Stephen A. Harrison, MD, from Pinnacle Clinical Research, San Antonio, Texas, and colleagues wrote. “Our findings support the potential of a novel EMM composition, AXA1125, to simultaneously address the multifactorial pathogenesis of NAFLD/[nonalcoholic steatohepatitis (NASH)], their key comorbidities, representing a unique modality with a coordinated multitargeted mechanism of action without major safety or tolerability issues. Future investigations are planned to assess the histological effects and longer term safety of AXA1125 in a double-blind, randomized, placebo-controlled, paired-biopsy trial over 48 weeks in individuals with biopsy-confirmed NASH.”
Harrison and colleagues performed a multicenter, 16-week placebo-controlled, single-blind trial of 102 patients with NAFLD, of whom 40 had type 2 diabetes. Patients were randomly assigned to AXA1125 24 g, AXA1957 13.5 g or 20.3 g or placebo administered twice daily. Investigators assessed key metabolism (MRI-proton density fat fraction [MRI-PDFF] and homeostasis model assessment of insulin resistance [HOMA-IR]) and fibroinflammation markers (alanine aminotransferase [ALT], corrected T1 [cT1], keratin-18 [K-18] M65, and N-terminal type III collagen propeptide [Pro-C3]). Adverse events and standard laboratory evaluations were among the safety outcomes.
“Baseline characteristics of the 102 enrolled subjects, including 40 with type 2 diabetes, were consistent with presumed nonalcoholic steatohepatitis,” Harrison and colleagues wrote. “AXA1125 showed consistently greater biologic activity than AXA1957 or placebo.”
Investigators noted changes from baseline to week 16 with AXA1125 compared with placebo in MRI-PDFF (22.9% vs. 5.7%), HOMA-IR (4.4 vs. 0.7), ALT (21.9% vs. 7.2%), K-18 M65 (13.6% vs. 20.1%.), (cT1 69.6 vs. 18.3) ms (P < .05), and Pro-C3 (13.6% vs. 3.6%). With AXA1957 20.3 g, changes from baseline to week 16 included MRI-PDFF 8.1%, HOMA-IR 8.4, ALT 20.7%, K-18 M65 6.6%, cT1 34.7 ms and Pro-C3 15.6%.
According to researchers, there were more patients treated with AXA1125 that achieved clinically relevant thresholds including 30% MRI-PDFF or greater reductions at week 16, 17 IU/L or greater in ALT, and 80 ms cT1 or greater reductions. Products were both safe and well tolerated by patients with stable lipid and weight profiles, according to Harrison and colleagues.