5 October 2020 - - French biopharmaceutical company Poxel SA (Euronext: POXEL) has released positive top-line results for STAMP-NAFLD, the PXL770 Phase 2a trial.

The Phase 2a trial was a 12-week, randomized, parallel group study, in 120 presumed NASH patients with or without diabetes. PXL770 is a first-in-class, oral direct adenosine monophosphate-activated protein kinase activator.

AMPK is a master regulator of several important metabolic pathways, including lipid metabolism, glucose control and inflammation, and is a novel target for NASH and a range of other chronic and rare metabolic diseases.

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.

Primary enrollment criteria were evidence of hepatic steatosis (NAFLD) based on a controlled attenuation parameter score of >300 db/m measured by MRI-PDFF.

Patients were randomized into four groups: PXL770 at 250 mg once-daily; 250 mg twice-daily; 500 mg once-daily versus patients who received placebo.

The Phase 2a trial met its primary efficacy endpoint; PXL770 was observed to produce 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 MRI-PDFF (p=0.0036 vs. -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; p=0.004 versus baseline).

The effects of PXL770 in this key subpopulation will be further evaluated within each treatment group.
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. The number of patients with treatment-emergent adverse events in each group were similar to placebo and these events were mainly mild-to-moderate.

The safety results from the Phase 2a trial are consistent with the PXL770 PK/PD trial and Phase 1 program.