Alnylam Pharmaceuticals

Alnylam Pharmaceuticals RSV—phase I AMD, DR, DME, SCI—preciinicai INFL, CF, PD—research... 

Alnylam Pharmaceuticals Respiratory syncytial virus infections Phase II clinical trial completed in November 2007 Administrated by nebulization Naked siRNA... 

Investigative Toxicology, Alnylam Pharmaceuticals Inc., Cambridge, MA, USA Bioinformatics, Alnylam Pharmaceuticals Inc., Cambridge, MA, USA... 

Muthiah Manoharan, Department of Drug Discovery, Alnylam Pharmaceuticals Inc, 300 Third Street, Cambridge, MA 02142... 

Alnylam Pharmaceuticals (2010a) Phase 2b study of ALN-RSVOl in lung transplant patients infected with respiratory syncytial virus (RSV). Available at http //clinicaltrials.gov/ct2/show/ NCT01065935. Last accessed 25 July 2011. US National Library of Medicine, Bethesda... 

Alnylam Pharmaceuticals Inc. (in a partnership with Tekmira Pharmaceuticals Corporation) completed a phase 1 clinical trial with a SNALP formulation (ALN-VSP02), containing two siRNAs targeting KSP and vascular endothelial growth factor... 

VEGF) in patients with advanced solid tumors with liver involvanent (Tabemero et al 2013). Using the DLin-DMA, Alnylam Pharmaceuticals Inc. developed another SNALP encapsulating a siRNA targeting transthyretin (ALN-TTROl) for the treatment of transthyretin mediated amyloidosis (ATTR) that in 2012 completed a phase 1 clinical trial (Table 14.1). 

DLin-DMA, as a starting point for a structure-activity relationship study, primed the identification of other ionizable cationic lipid even more potent for hepatic gene silencing in vivo, such as l,2-dilinoleyloxy-keto-A,A-dimethyl-3-aminopropane (DLin-K-DMA), l,2-dilinoteyl-4-(2-dimethylaminoethyl)-[ 1,3]-dioxolane (DLin-KC2-DMA Semple et al., 2010) and heptatriaconta-6,9,28,31-telraen-19-yl 4-(dimelhylamino) butanoate (DLin-MC3-DMA Jayaraman et al., 2012). This later promising cationic lipid was used for the preparation of second-generation SNALP-siRNA formulations by Alnylam Pharmaceuticals Inc. 

In 2015, Alnylam Pharmaceuticals Inc. presented initial data from a phase 1 trial of ALN-PCSsc (NCT02314442) in subjects with elevated LDL cholesterol (LDL-C). Subcutaneous administration of ALN-PCSsc resulted in 83% lowering of LDL-C, at dose of 300mg. The effects were highly dmable, with clinically significant reductions in LDL-C maintained for over 140 days, thus supporting a once-quarterly and possibly bi-annual subcutaneous dose regimen. 

---