Poxel announced positive results from the phase 2a STAMP-NAFLD trial, which evaluated PXL770 in patients with non-alcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD). The trial met the primary endpoint of decrease in liver fat mass, as well as secondary endpoints including improvements in liver enzymes. The Phase 2a results will be submitted for presentation at an upcoming scientific meeting.
STAMP-NAFLD was a 12-week randomized, placebo-controlled, parallel group trial in 120 presumed NASH patients, with or without diabetes, which evaluated three dosing regimens of PXL770 versus placebo. Patients were randomized into four groups: PXL770 at 250 mg once-daily (QD); 250 mg twice-daily (BID); 500 mg once-daily (QD) or placebo.
PXL770 produced a statistically significant mean relative decrease of 18% in liver fat mass from baseline at 12-weeks in the 500 mg QD dose group as measured by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF) versus -0.7% change in placebo. A greater proportion of patients who received PXL770 also achieved a >30% relative reduction in liver fat content compared to placebo; greater liver fat content reduction (up to -85%) was also observed in more responsive patients. Although mean baseline ALT values (37-41 U/L) were near the upper range of normal, a statistically significant reduction in mean ALT was also observed in the 500 mg dose group.
In patients with type 2 diabetes (41-47% of each group), PXL770 treatment resulted in a greater mean relative reduction in liver fat content (-27% at 500 mg QD versus baseline).
Despite nearly normal mean baseline HbA1c values (6.03-6.30%) across all groups (patients with and without diabetes), a significant reduction in mean HbA1c was also observed. A similar trend was also observed on fasting plasma glucose.
PXL770 was observed to be generally safe and well tolerated.
PXL770 is a first-in-class direct adenosine monophosphate-activated protein kinase (AMPK) activator. AMPK is a central regulator of multiple metabolic pathways leading to the control of lipid metabolism, glucose homeostasis and inflammation. Based on its central metabolic role, targeting AMPK offers the opportunity to pursue a wide range of indications to treat chronic metabolic diseases, including diseases that affect the liver, such as non-alcoholic steatohepatitis (NASH).
Non-alcoholic steatohepatitis (NASH) is a metabolic disease with no clear disease origin that is quickly becoming a worldwide epidemic. It is characterized by the accumulation of fat in the liver causing inflammation and fibrosis. The disease can be silent for a long period of time, but once it accelerates, severe damage and liver cirrhosis can occur, which can significantly impact liver function and can even result in liver failure or hepatocellular cancer. Typical risk factors for NASH include obesity, elevated levels of blood lipids (such as cholesterol and triglycerides) and diabetes. Currently no curative or specific therapies are available.