The Phase 2a trial for the treatment of NASH met its primary efficacy endpoint; PXL770-treated patients achieved statistically significant improvement in the relative decrease in liver fat mass measured by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF) at 12-weeks with a greater response in patients with type 2 diabetes1
Key secondary measures in PXL770-treated patients included statistically significant observed improvements in liver enzymes – alanine transaminase (ALT) and hemoglobin A1c (HbA1c)
PXL770 was observed to be safe and well tolerated; profile supports further evaluation for combination use
First human clinical assessment of a direct AMPK activator; results support potential for development in NASH including key high-risk subgroups (patients with type 2 diabetes) and utility of AMPK activation in other chronic and rare metabolic diseases
Conference call in English scheduled today for 12:00 pm EDT (New York time) / 6 pm CEST (Paris time)
POXEL SA (Euronext: POXEL – FR0012432516), a biopharmaceutical company focused on the development of innovative treatments for metabolic disorders, including type 2 diabetes and non-alcoholic steatohepatitis (NASH), today announced 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 (AMPK) 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.
“The underlying pathophysiological drivers of nonalcoholic fatty liver disease (NAFLD) and NASH are highly complex and support the need for development of novel therapies acting on different targets that can address a variety of key disease drivers,” said Vlad Ratziu, MD, PhD, Professor of Hepatology, Sorbonne University and Pitié-Salpêtrière Hospital. “AMPK activation is a differentiated approach for NASH and these results demonstrate that it could have a beneficial role in controlling key pathways that lead to liver injury. By also directly targeting inflammation and fibrogenesis, as demonstrated in preclinical models including human cells, PXL770 has the potential to independently impact multiple disease components. As an oral agent, PXL770 also has the potential to be used in combination with other agents, which could provide for broad treatment of this disease.”
Summary of STAMP-NAFLD PXL770 Phase 2a Study Results
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 (CAP) score of >300 db/m measured by MRI-PDFF. Patients were randomized into four groups: PXL770 at 250 mg once-daily (QD); 250 mg twice-daily (BID); 500 mg once-daily (QD) 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