DeuteRx LLC, a Boston-based biotechnology company dedicated to the improvement of marketed and candidate drugs, recently announced it will give an oral presentation on its candidate product DRX-065 at the ongoing American Association for the Study of Liver Diseases (AASLD) Annual Meeting. The presentation, entitled “DRX-065, the stabilized R-enantiomer of pioglitazone, is without PPARγ-agonist activity and exhibits the beneficial in vivo pharmacodynamic effects for the treatment of NASH,” is set for Nov. 16.
Non-alcoholic steatohepatitis (NASH) is a liver disease characterized by fat accumulation together with inflammation and damage. NASH occurs in individuals who drink little or no alcohol, and the condition is often “silent” with patients being unaware of their problem. NASH can become a severe condition and lead to cirrhosis, in which the liver is irreversibly damaged and scarred, and its function compromised. NASH is estimated to affect 2% to 5% of the American population.
There is a growing body of evidence supporting that NASH is a mitochondrial disease, in which mitochondrial dysfunction (particularly a respiratory chain deficiency) plays a key role in the disease’s pathophysiology. The generation of harmful reactive oxygen species (ROS) by the deficient mitochondrial respiratory chain increases in NASH, ultimately contributing to liver inflammation and fibrosis.
DeuteRx’s DRX-065 is an analog of pioglitazone, an oral anti-diabetic medicine that helps control blood-sugar levels. The compound is based on the company’s pioneering strategy known as deuterium-enabled chiral switching (DECS), a method developed to improve drug formulation and stabilize its active ingredients. DRX-065 is under development as a therapy for NASH and adrenoleukodystrophy, a genetic disease linked to the accumulation of specific fatty acids in tissues throughout the body.
DRX-065 was previously shown to have pharmacological properties important for the treatment of NASH, namely, it can modulate mitochondrial function, has non-steroidal anti-inflammatory effects, and is able to reduce glucose levels. Furthermore, these therapeutic actions were not accompanied by side effects like weight gain.
“Pioglitazone is one of the most widely studied drugs in NASH patients. Although clinical trial results are promising, pioglitazone’s use for the treatment of NASH is limited due to the adverse side effects of weight gain and fluid retention. DeuteRx’s preclinical data with the stabilized R-enantiomer of pioglitazone, DRX-065, offers the prospect of separating the undesired weight gain and fluid retention from the beneficial therapeutic properties for NASH,” explained Dr. Scott Friedman, consultant to DeuteRx in a news release. “DRX-065 represents a potentially significant therapeutic improvement over pioglitazone for NASH patients.”
The AASLD 2015 meeting runs Nov. 13-17 in San Francisco.