Alnylam welcomes you to Capella, the destination for updates on our progress in translating the science of RNAi toward innovative medicines.
December 23, 2013Novel Method for Detection of Tissue-Specific, RNAi-Mediated Gene Silencing Published in “RNA”
We have published a paper in the journal RNA describing a novel method that enables the quantification of circulating messenger RNA (mRNA) and micro-RNA (miRNA) as a way of monitoring tissue-specific RNA silencing, and demonstrating RNAi mechanism of action. The method, called circulating Extracellular RNA Detection (cERD), could have broad applicability in clinical studies since it allows for monitoring of tissue-specific mRNA levels using a non-invasive technique.
December 19, 2013Pre-Clinical Data on Pharmacology of GalNAc-siRNA Conjugates
We presented new pre-clinical data on the pharmacology of GalNAc-siRNA conjugates at the 12th US-Japan Symposium on Drug Delivery Systems held December 16 – 20, 2013 in Lahaina, Maui, Hawaii. These new research findings describe the effects of long-term chronic dosing of GalNAc-siRNA conjugates on tissue drug levels and sustained target knockdown.
December 9, 2013Pre-Clinical Data from “Alnylam 5×15” Programs Presented at ASH 2013
We presented pre-clinical data from three programs within our “Alnylam 5×15” RNAi therapeutic pipeline: ALN-AT3 for the treatment of hemophilia and rare bleeding disorders (RBD), ALN-CC5 for the treatment of complement-mediated diseases, and ALN-TMP for the treatment of β-thalassemia and iron overload disorders. These data were presented at the 55th Annual Meeting of the American Society of Hematology (ASH) held December 7 – 10 in New Orleans.
November 17, 2013New Pre-Clinical Data on ALN-PCSsc and ALN-ANG Presented at AHA
We presented new pre-clinical data with RNAi therapeutic programs for cardiovascular disease: ALN-PCSsc, an RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia; and ALN-ANG, an RNAi therapeutic targeting ANGPTL3 for the treatment of genetic forms of mixed hyperlipidemia and severe hypertriglyceridemia. These data were presented at the American Heart Association (AHA) Scientific Sessions held November 16 – 20, 2013 in Dallas, Texas. The data showed that subcutaneous administration of ALN-PCSsc led to an up to 95% knockdown of plasma PCSK9 and an up to 67% reduction of low density lipoprotein cholesterol (LDL-C) – in the absence of statin co-administration. In addition, new results for ALN-ANG demonstrated a greater than 95% reduction of triglycerides and greater than 85% reduction of LDL-C in a rodent model of mixed hyperlipidemia.
November 16, 2013ALN-ANG Historical Press Releases
For your convenienence we have collected a list of historical press releases that cover the historical progess of our clinical program for mixed hyperlipidema and severe hypertriglyceridemia
November 10, 2013Positive Phase II Data with Patisiran (ALN-TTR02)
We presented positive data from our Phase II clinical trial of patisiran (ALN-TTR02) for the treatment of transthyretin-mediated amyloidosis (ATTR) at the International Symposium on Familial Amyloidotic Polyneuropathy, November 10 – 13, 2013. Results showed that multiple doses of patisiran led to robust and statistically significant knockdown of serum TTR protein levels of up to 96%, with mean levels of TTR knockdown exceeding 85%. Knockdown of TTR, the disease-causing protein in ATTR, was found to be rapid, dose dependent, and durable, and similar activity was observed toward both wild-type and mutant protein. In addition, patisiran was found to be generally safe and well tolerated in this study.
November 2, 2013New Pre-Clinical Data on ALN-AAT for the Treatment of Alpha-1-Antitrypsin (AAT) Deficiency Liver Disease
We presented new pre-clinical data on ALN-AAT, an RNAi therapeutic targeting alpha-1 antitrypsin (AAT) in development for the treatment of liver disease associated with AAT deficiency. These data were presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD, “The Liver Meeting”) held November 1 – 5, 2013. In a transgenic mouse model of Z-AAT protein over-expression, subcutaneous administration of a GalNAc-siRNA targeting AAT led to rapid, potent, dose-dependent, and durable knockdown of AAT of greater than 90%, as well as a significant reduction in fibrosis and the incidence of liver tumors.
October 8, 2013New Pre-Clinical Data on ALN-AS1 for the Treatment of Porphyria and PK/PD Properties of GalNAc-siRNA Conjugates
We presented new pre-clinical data supporting the selection of the ALN-AS1 Development Candidate for the treatment of hepatic porphyrias, including acute intermittent porphyria (AIP). The new research, presented at the 9th Annual Meeting of the Oligonucleotide Therapeutics Society, held October 6 – 8, 2013 in Naples, Italy, showed that multi-dose administration of a GalNAc-siRNA targeting ALAS-1 led to rapid, dose-dependent, and long-lasting knockdown of the ALAS-1 mRNA in non-human primates, with an ED50 of approximately 1.25 mg/kg. Further, in a rat model of AIP, ALN-AS1 administration at doses as low as 2.5 mg/kg resulted in a complete blunting of phenobarbital-induced over-production of PBG and ALA, the toxic heme intermediates in AIP.
October 3, 2013Positive Phase I Clinical Trial Results with ALN-PCS Published in “The Lancet”
We have published complete study results from our Phase I trial with ALN-PCS in The Lancet. As reported in the paper, ALN-PCS administration resulted in a rapid, dose-dependent reduction in plasma PCSK9 of up to 84% relative to baseline and placebo, with a corresponding reduction in serum levels of low-density lipoprotein cholesterol (LDL-C) – or “bad” cholesterol – of up to 57% relative to baseline and placebo. The knockdown of PCSK9 and lowering of LDL-C were also found to be durable, with effects lasting for weeks after a single dose. In addition, ALN-PCS was shown to be generally safe and well tolerated in this Phase I study and there were no serious adverse events related to study drug administration. This new paper documents the first human proof of concept for an RNAi therapeutic impacting a clinically validated endpoint, namely LDL-C.
September 23, 2013Positive Clinical Results from Phase I Trial of ALN-TTRsc
We have reported positive clinical results from our Phase I trial of ALN-TTRsc, a subcutaneously administered RNAi therapeutic targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR). Data were presented at the Heart Failure Society of America 17th Annual Scientific Meeting being held September 22 – 25. These results demonstrated that ALN-TTRsc achieved robust, consistent, and statistically significant (p<0.01) knockdown of serum TTR protein levels of up to 94%. In addition, knockdown of TTR was found to be rapid, dose-dependent, and durable. ALN-TTRsc was found to be generally safe and well tolerated in this study.