Arrowhead Pharmaceuticals Inc. (NASDAQ:ARWR) has announced positive provisional results of the 24-week liver biopsy AROAAT2002 open-label second phase clinical trial of ARO-ATT. ARO-ATT is the company’s 2nd generation experimental RNA interference therapeutics under development for treating genetic liver disease-related to Alpha-1 antitrypsin deficiency (AATD).
ARO-AAT demonstrates pharmacodynamics benefit
According to the study results, ARO-AAT demonstrated signs of significant pharmacodynamics effect, resulting in improvements in the relevant biomarkers that include substantial intra-hepatic mutant AAT protein (Z-AAT), Z-AAT polymer, and Z-AAT monomer reduction. Also, based on a FibroScan, there were improvements in liver stiffness. Another benefit was the drop in gamma-glutamyl transferase (GGT) and alanine aminotransferase (ALT), which are liver injury serum biomarkers.
Four patients who received ARO-AAT in the study showed decreased total intrahepatic Z-AAT and serum after treatment for 24-weeks by around 93% and 95%. Three-quarters of the patients showed a drop from baseline in the intra-hepatic Z-AAT polymer with a reduction of around 97%. There was GGT and ALT reductions of 58% and 66%, respectively in all four patients. All patients also showed enhanced transient elastography FibroScan values, whereby 75% of the study participants exhibited more than 20% reductions.
Positive results clear clinical and regulatory path for Arrowhead
Arrowhead’s Chief Medical Officer, Javier Smith, said that the company had expected 6 months of investigational ARO-AAT treatment in the second phase study to result in significant Z-AAT monomer reduction. However, there was an improvement in clinically significant biomarkers that included Z-AAT polymer and FibroScan Values improvement and a substantial decrease in GGT and ALT than anticipated. Smith added that the results are exciting, and they offer enhanced confidence regarding the program’s potential. Based on data, the company is assessing its clinical and regulatory pathway, including discussions with the FDA to identify streamlining areas and accelerate the program.
The study’s lead investigator, Professor Pavel Strnad, said that the data was promising, which suggests that ARO-AAT can quickly improve liver injury. Pavel added that it was good to see a drop in liver enzymes, which indicates that the elevated levels assorted to proteotoxic stress can be dealt with by ARO-AAT therapy.