LYON - 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 results from a PXL770 four-week placebo-controlled PK/PD study in 16 likely-NASH patients with insulin resistance.
The primary objective of the study was to assess the full pharmacokinetic (PK) profile of PXL770 as well as to evaluate safety and tolerability. PXL770 is a first-in-class direct adenosine monophosphate-activated protein kinase (AMPK) activator, which is being evaluated for the treatment of NASH. 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.
In the results observed from the PK/PD trial, PXL770 met its study objectives showing a PK profile in likely-NASH patients that was similar to the one observed in healthy volunteers in the Company's Phase 1 program. In the PK/PD trial, PXL770 was also observed to be safe and well-tolerated. PXL770 induced a statistically significant suppression of de novo lipogenesis (DNL) known to be one of the important contributors to the progression of NASH. A statistically significant effect was also observed on glucose tolerance during a glucose challenge test (OGTT) in this population of non-diabetic patients. This trial confirmed the target engagement of PXL770 on the AMPK pathway and the potential of the drug in other metabolic diseases.
'We are pleased with these results in likely-NASH patients; they confirm that target engagement in patients has been achieved and that some of the effects observed with PXL770 in various preclinical models can be translated in the clinic. They also support the role of AMPK as an important player in the NASH pathophysiology as suggested in published literature,' commented Pascale Fouqueray, MD, PhD, Executive Vice President, Clinical Development and Regulatory Affairs at Poxel.
'These results support our hypothesis that AMPK activation could have a beneficial role in controlling key pathways that lead to liver injury and NASH, and these data provide additional understanding of this novel mechanism,' said Thomas Kuhn, CEO of Poxel. 'We look forward to the upcoming results from the Phase 2a study, which is evaluating PXL770 in approximately 100 likely-NASH patients. Topline results from the study are expected toward the end of the third quarter in 2020.'
'AMPK is a compelling pharmaceutical target and we are encouraged by the outcome of this study. Not only does the data further demonstrate the potential for PXL770 in NASH, the positive effects on DNL and OGTT suggest that AMPK activation may be useful in addressing a broader range of other diseases mediated by metabolic pathway dysfunction,' said David E. Moller, MD, Chief Scientific Officer of Poxel. 'Thus, we are also currently evaluating our library of AMPK targeted molecules which could have the potential to expand our pipeline into programs for other chronic and rare metabolic diseases.'
About the PXL770 PK/PD Study
The four-week PK/PD study was conducted to assess the full PK profile, and safety and tolerability of PXL770 in 16 likely-NASH patients with insulin resistance. Primary enrollment criteria were evidence of hepatic steatosis (NAFLD) based on a controlled attenuation parameter (CAP) score of >300 db/m measured by transient elastography (FibroScan) along with a HOMA-IR (calculated measure of insulin resistance) score >2.5. Patients were randomized into two groups; twelve patients were administered PXL770 at 500 mg once-daily versus four patients who received placebo. The study assessed the effect of PXL770 on several target pathways, including hepatic DNL, glucose tolerance, as well as other fasting biomarkers.
The observed PK profile of PXL770 at the dose of 500 mg once-daily in these likely-NASH patients was consistent with results obtained in the Company's Phase 1 program in healthy subjects.
Relative to baseline measurements, PXL770 treatment was observed to produce statistically significant (p=0.0045) suppression of DNL along with a statistically significant (p