Non-Alcoholic Steatohepatitis or NASH is a common liver disease. It is similar to alcoholic liver disease, but occurs in people who drink little or no alcohol. The major feature in NASH is fat in the liver, along with inflammation and fibrosis. NASH affects 2 to 5 percent of Americans.

NASH is widely considered to be the liver expression of the metabolic syndrome (diseases related to diabetes mellitus type 2, insulin resistance, central (truncal) obesity, hyperlipidemia (low high-density lipoprotein cholesterol, hypertriglyceridemia), and hypertension. Approximately 6 million individuals in the USA are estimated to have progressed from NAFLD to NASH and some 600,000 to NASH-related cirrhosis. NASH is regarded as a major cause of cirrhosis of the liver of unknown cause.

Although several treatment options are being evaluated, the value of most treatments remains uncertain, or the effects reverse when they are discontinued. The goals of treatment for NASH are to reduce the histologic features and improve insulin resistance and liver enzyme levels. At the present time, there is no evidence-based approved drug therapy for NAFLD/NASH.

The robust hepatoprotective activity of VLX103 combined with its very good safety profile provides Verlyx with a unique opportunity to develop a safe and potent novel approach to treat NASH.

Phase I completed

Verlyx has completed a phase I clinical study evaluating VLX103. This is a randomized, double-blind, placebo-controlled, sequential-group administration of a new oral form of pentamidine to investigate its hepatic uptake, pharmacokinetics, safety and tolerability. Results from this trial allow Verlyx to select specific doses to be used in subsequent Phase II trials.

Primary Objective

Liver concentration of pentamidine after oral administration for three days at different doses, measured in liver biopsies obtained during thermal ablation or partial hepatectomy procedures.

Secondary Objectives

Plasma concentration of pentamidine after oral administration for three days at different doses, safety as assessed by adverse events, vital signs and laboratory parameters. Plasma pharmacodynamic markers of anti-inflammatory/hepatoprotection efficacy (e.g. ALT and AST) will be monitored.

The abstracts detailing these results were presented at the American Association for the Study of Liver Disease (AASLD) in 2016. Abstracts #641 and #642 at the Liver Meeting®, in Boston, in November 2016 are available below.

Phase II in NASH

 Verlyx is currently planning a randomized phase II in NASH.