Date: 2014-11-17
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the American Heart Association (AHA) Scientific Sessions 2014
Company: Alnylam Pharmaceuticals (USA - MA)
Product: ALN-AC3
Action
mechanism: ALN-AC3 is a subcutaneously administered investigational RNAi therapeutic targeting apoC3 for the treatment of hypertriglyceridemia. ApoC3 is a component of lipoprotein particles in the blood; it inhibits lipoprotein lipase and hepatic lipase, reducing hepatic uptake of triglyceride-rich particles. Polymorphisms in apoC3 have been associated with hypertriglyceridemia; specifically, a gain-of function phenotype leads to higher apoC3 and triglyceride levels, and reduced triglyceride clearance. In contrast, loss-of-function mutations in apoC3 result in greater triglyceride hydrolysis into free fatty acids and increased triglyceride clearance; heterozygous individuals have lower triglycerides and lower levels of very low density lipoprotein (VLDL). Recent studies have identified rare loss of function variants in apoC3 that appear to be cardioprotective (Tachmazidou et al., Nat. Comm, 2013; Bochem et.al. Clin Genet., 2014).
Disease: hypertriglyceridemia
Therapeutic area: Cardiovascular diseases - Metabolic 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-AC3 targeting apolipoprotein C3 (apoC3) for the treatment of 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 presented data from its ALN-AC3 program at AHA. The new data presented were from studies conducted in mouse models that match human genetics. Specifically, a single 3 mg/kg dose of a GalNAc-conjugated siRNA targeting apoC3 resulted in knockdown of apoC3 levels of up to 94%, with more than 60% knockdown sustained for at least 30 days. In a multi-dose study, results showed that dosing of 3 mg/kg every other week resulted in 96% knockdown of human apoC3 through day 35, the last time point in the study. Alnylam plans to continue to conduct additional pre-clinical work in this program to finalize its Development Candidate.
