Arrowhead Pharmaceuticals, Inc. announced that it has dosed the first subject in the YOSEMITE Phase 3 clinical trial of zodasiran, the company's investigational RNA interference (RNAi) therapeutic being developed as a potential treatment for homozygous familial hypercholesterolemia (HoFH), a rare genetic condition that leads to severely elevated LDL-cholesterol and early onset cardiovascular disease. Zodasiran is the fourth investigational RNAi-based candidate developed by Arrowhead to reach late-stage pivotal studies, after investigational drugs plozasiran, fazirsiran (licensed to Takeda) and olpairan (licensed to Amgen). As an RNAi-based therapeutic targeting ANGPTL3, investigational zodasiran has the potential to treat HoFH in a fundamentally different manner from traditional LDL-C-lowering therapies.
In Phase 2 clinical studies, patients with HoFH receiving zodasiran achieved reductions from baseline in LDL-C, ApoB, non-HDL-C, and triglycerides, supporting its potential therapeutic role for the treatment of HoFH patients. Homozygous Familial Hypercholesterolemia (HoFH) is an ultra-rare treatment-resistant genetic condition characterized by elevated low density lipoprotein cholesterol (LDL-C) and early-onset cardiovascular disease. The primary endpoint is the percent change from baseline to month 12 in fasting LDL-C. After month 12, eligible participants will be offered an opportunity to continue in an optional open-label extension.
Zodasiran, previously called ARO-ANG3, is a first-in-class investigational RNA interference (RNAI) therapeutic designed to reduce production of angiopoietin-like protein (ANGPTL3), which is a hepatocyte expressed regulator of lipid and lipoprotein metabolism with multiple potential modes of action, including inhibition of lipoprotein lipase (LPL) and endothelial lipase (EL)5,6. ANGPTL3 is an emerging therapeutic target with relevance to hypercholesterolemia, hypertriglyceridemia, and mixed hyperlipidemia. Genetic studies suggest that individuals with ANGPTL3 loss-of-function variants have enhanced lipoprotein lipase and endothelial lipase activity, resulting in lower levels of atherogenic lipoproteins and a reduced risk of ASCVD2-4. In addition, any statements that refer to projections of future financial performance, trends in business, expectations for product pipeline or product candidates, including anticipated regulatory submissions and clinical program results, prospects or benefits of collaborations with other companies, or other characterizations of future events or circumstances are forward-looking statements. These forward-looking statements include, but are not limited to, statements about the initiation, timing, progress and results of preclinical studies and clinical trials, and research and development programs, and research and development programs; expectations regarding regulatory approval for and commercial launch of plozasiran; expectations regarding the potential benefits of the partnership, licensing and/or collaboration arrangements and other strategic arrangements and transactions they have entered into or may enter into in the future; expectations regarding the potential benefits the partnership, licensing and/or/or collaboration arrangements and other Strategic arrangements and transactions they have entered in the future; expectations regarding milestone, royalty or other payments that could be due to or from third parties under existing agreements; and estimates regarding future revenues, research and development expenses, capital requirements and payments to third parties.
