Arrowhead Pharmaceuticals Inc. (ARWR:NASDAQ), which is focused on developing medicines that treat intractable diseases by silencing the genes that cause them, today announced "positive interim 24-week liver biopsy results in four subjects from AROAAT2002, an open-label Phase 2 clinical study of ARO-AAT, the company's second generation investigational RNA interference (RNAi) therapeutic being developed as a treatment for the rare genetic liver disease associated with alpha-1 antitrypsin deficiency (AATD)."
The company stated that the results obtained demonstrate meaningful pharmacodynamic effects by ARO-AAT that led to improvements in several relevant biomarkers. The firm indicated specifically that the results showed "substantial reductions in intra-hepatic mutant AAT protein (Z-AAT), both Z-AAT monomer and Z-AAT polymer, improvements in liver stiffness based on FibroScan and a decrease in alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), both serum biomarkers of liver injury."
The company advised that in the pilot AROAAT2002 study of investigational ARO-AAT, serum and total intra-hepatic Z-AAT decreased in all four patients by up to 93% and 95%, respectively, following 24 weeks of treatment. In addition, the firm noted that all four patients showed reductions in ALT and GGT and three of four patients demonstrated reductions from baseline in intra-hepatic Z-AAT polymer, with a maximum reduction of 97%.
Arrowhead Pharmaceuticals Chief Medical Officer Javier San Martin commented, "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."
AROAAT2002 trial investigator Professor Pavel Strnad, M.D., of University Hospital Aachen in Germany, remarked, "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."
Mark Brantly, M.D., scientific director of the Alpha-1 Foundation, added, "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."
The company explained that the Phase 2 AROAAT2002 trial is a multi-dose pilot study to assess the responses of around 16 patients with AATD associated liver disease to ARO-AAT. The firm stated that ARO-AAT is also presently being evaluated in an ongoing Phase 2/3 SEQUOIA trial that commenced in August 2019.
Arrowhead Pharmaceuticals, headquartered in Pasadena, Calif., stated that its therapies utilize RNA chemistries and efficient modes of delivery to trigger RNA interference (RNAi) mechanisms in order to induce rapid, deep and durable knockdown of target genes. The firm explained that RNAi is a response characteristic present in living cells that affects the production of a specific protein by inhibiting the expression of a specific gene. Arrowhead claimed that its RNAi-based therapeutics take advantage of this natural gene silencing pathway.
Arrowhead Pharmaceuticals started the day with a market capitalization of around $3.5 billion with approximately 102.3 million shares outstanding and a short interest of about 9.2%. ARWR shares opened 18.5% higher today at $40.05 (+$6.25, +18.49%) over yesterday's $33.80 closing price. The stock has traded today between $40.05 and $53.12 per share and is currently trading at $49.90 (+$16.10, +47.63%).[NLINSERT]
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