Date: 2014-11-17
Type of information: Initiation of development program
phase:
Announcement: initiation of development program
Company: Alnylam Pharmaceuticals (USA - MA)
Product: ALN-ANG
Action
mechanism: ALN-ANG, an investigational RNAi therapeutic targeting ANGPTL3 for the treatment of genetic forms of mixed hyperlipidemia and severe hypertriglyceridemia. ANGPTL3 is an inhibitor of cellular lipases involved in the metabolism of lipoproteins.
Disease: genetic forms of mixed hyperlipidemia and severe hypertriglyceridemia
Therapeutic area: Cardiovascular diseases - Metabolic diseases - Genetic diseases
Country:
Trial details:
Latest
news: * On November 17, 2014, Alnylam Pharmaceuticals, a leading RNAi therapeutics company, announced that it has presented new pre-clinical data from its investigational RNAi therapeutic programs toward genetically validated targets in development for the treatment of cardiovascular metabolic diseases, including ALN-ANG targeting angiopoietin-like 3 (ANGPTL3) for the treatment of genetic forms of mixed hyperlipidemia and severe hypertriglyceridemia. These new data are being presented at the American Heart Association (AHA) Scientific Sessions 2014 in a poster presentation titled “Development of Monthly to Quarterly Subcutaneous Administration of RNAi Therapeutics Targeting the Metabolic Disease Genes PCSK9, ApoC3 and ANGPTL3.” Among other data, Alnylam announced that the company is also advancing ALN-ANG, an investigational RNAi therapeutic targeting ANGPTL3 for the treatment of genetic forms of mixed hyperlipidemia and severe hypertriglyceridemia. ANGPTL3 is an inhibitor of cellular lipases involved in the metabolism of lipoproteins. Human genetic as well as exome sequencing studies have identified a statistically significant relationship of loss-of-function mutations in ANGPTL3 with decreased levels of triglycerides and LDL-C (Musunuru et al., N. Engl. J. Med (2010) 363:2220-2227). New data presented at AHA demonstrated that a single dose of a GalNAc-siRNA targeting ANGPTL3 led to robust, dose-dependent knockdown of serum ANGPTL3 protein of up to 99%, with a single dose ED90 of approximately 1 mg/kg. In studies performed in an “ob/ob” mouse model of obesity and mixed hyperlipidemia, ALN-ANG treatment as a single 3 mg/kg dose resulted in a greater than 80% reduction in levels of triglycerides and LDL-C. In addition, total cholesterol was reduced up to 68%. These data with ALN-ANG support further advancement of this program for the treatment of genetic forms of mixed hyperlipidemia and severe hypertriglyceridemia, which are associated with increased risk of coronary artery disease and/or recurrent pancreatitis. Alnylam is conducting additional pre-clinical research to finalize its Development Candidate for the ALN-ANG program.
