Research on the treatment for the cure of Alpha 1 Deficiency continues to advance

The second phase of treatment is already underway

Arrowhead ARO-AAT Phase 2 interim results in patients with alpha-1 liver disease demonstrate improvements in key parameters after six months of treatment.

PASADENA, California

Arrowhead Pharmaceuticals Inc. announced this September 2020 interim positive 24-week liver biopsy results in four subjects from AROAAT2002.

An open-label phase 2 clinical study of ARO-AAT, in conjunction with RNA interference, has been conducted in the company’s second-generation research (RNAi), which is developing a treatment for rare liver disease, associated with alpha-1 antitrypsin deficiency (AATD).

 The results of the analysis have been positive, showing the following data:

– Up to 97% reduction in intra-hepatic Z-AAT polymer.

– Up to 95% reduction in intra-hepatic total Z-AAT burden.

– Up to 66% and 58% reduction in circulating ALT and GGT levels respectively.

– Up to 26% improvement in FibroScan values.

Study conclusion

The results show clear evidence for a significant pharmacodynamic effect of ARO-AAT, leading to improvements in relevant biomarkers, including substantial reductions in intrahepatic mutant AAT protein (Z-AAT), both the Z-AAT monomer and the Z polymer. -AAT; FibroScan-based improvements in liver stiffness; and a decrease in alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), both serum biomarkers of liver injury.

Encouraging data for science

After 24 weeks of treatment with investigational ARO-AAT in study AROAAT2002, total and serum intrahepatic Z-AAT decreased in all four patients by up to 93% and 95%, respectively. Three of four patients demonstrated reductions from baseline in intrahepatic polymer Z-AAT, with a maximum reduction of 97%. All four patients showed reductions in ALT and GGT, with maximum reductions of 66% and 58%, respectively. All patients demonstrated better transient elastography FibroScan values, with three out of four patients showing reductions greater than 20%.

United by science

Arrowhead provided a late-breaking summary of the 24-week interim results for the first AROAAT2002 cohort in which 4 patients received ARO-AAT 200 mg at weeks 1, 4, and 16 and, if accepted, intends to Present additional data at the American Association for the Study of Liver Disease (AASLD) Liver Meeting in November 2020.

The opinion of the experts and collaborators of the medical trial

Professor Pavel Strnad, M.D., University Hospital Aachen, Germany, and an investigator on the trial, said: “These data are very encouraging and suggest that ARO-AAT may rapidly ameliorate liver injury. It is particularly reassuring to see the decrease in liver enzymes, which suggests that elevations are related to proteotoxic stress that could be addressed with ARO-AAT therapy rather than reflecting co-morbidities. In addition, no major lung events have occurred in this study to date, which indicates that RNAi-based reduction of Z-AAT in the liver has not negatively affected lung function during the treatment period. I am pleased that all of my patients have opted to continue on study for the 12-month extension, and I am eager to follow their progress.”

Javier San Martin, M.D., chief medical officer at Arrowhead, said: “While we had anticipated that 6 months of treatment with investigational ARO-AAT in the Phase 2 open label study would likely lead to substantial reductions in Z-AAT monomer, the improvements in additional clinically meaningful biomarkers, including reductions in Z-AAT polymer, improvements in FibroScan values, and decreases in ALT and GGT, were more substantial than we expected. These are very exciting results and provide us with increased confidence in the potential of this program. Based on these important data, we are actively assessing our clinical and regulatory path forward, including engaging with the U.S. Food and Drug Administration and other regulatory agencies, to identify areas where the program could potentially be streamlined and accelerated.”

Miriam O’Day, President & CEO of the Alpha-1 Foundation, stated: “The news regarding the Arrowhead ARO-AAT Phase 2 interim results for liver treatment in Alpha-1 Antitrypsin Deficiency brings hope to the Alpha-1 community in the midst of the COVID-19 pandemic. It is critically important that new treatments for patients who currently do not have therapeutic interventions move forward and encourages our optimism as we reimagine treatment for this condition and its underserved patient population.”

Mark Brantly, M.D., Scientific Director, Alpha-1 Foundation, stated: “The Arrowhead ARO-AAT Phase 2 open label clinical trial is exciting for the Alpha-1 community as it brings forward an intervention for the liver disease associated with Alpha-1 Antitrypsin Deficiency. The interim result of this study demonstrates proof of principle that RNA interference is a promising therapy for the liver disease associated with Alpha-1 Antitrypsin Deficiency. Alpha-1 Foundation is devoted to developing treatments for the Alpha-1 community by directly funding research, partnering with industry collaborators and supporting a research registry to accelerate the completion of clinical trials. This news is exciting and offers hope for the Alpha-1 community who joins us in celebrating this accomplishment and each step that moves our community closer to a cure.”

Centro Andaluz Alfa-1