.. _alynylam: .. index:: biotech Alnylam Pharmaceuticals ======================== Alnylam Pharmaceuticals is a biopharmaceutical company focused on the discovery, development and commercialization of RNA interference (RNAi) therapeutics for genetically defined diseases. The company was founded in 2002 and is headquartered in Cambridge, Massachusetts. In 2016, Forbes included the company on its "100 Most Innovative Growth Companies" list. Therapeutic concept +++++++++++++++++++++++ Main article: RNA interference Most drug discovery seeks molecules which associate with a "target" associated with a disease and interfere with its function, thus remediating the disease at a molecular level. Examples include small molecule HIV protease inhibitors, which are taken orally, and via the bloodstream, make their way to cells infected with the HIV virus, and block a key enzyme, virally encoded enzyme, HIV protease, by occupying its active site, thereby refusing access of a key viral component, and preventing a key step in the HIV virus life cycle (scission of the HIV polyprotein). A different approach targets the production of a protein required for the development of the disease. RNAi was discovered to be a natural mechanism for silencing genes through cleavage and degradation of mRNA, first discovered in C. elegans in 1998 by Andrew Fire and Craig Mello.[28] Genes encode the information necessary for cells to synthesize proteins, and proteins made abnormally cause many human diseases. When a mutant gene is silenced, the cell stops making the abnormal protein specified by that gene, potentially improving the course of the disease. In 2001, Alnylam founders began using small interfering RNAs, known as siRNAs, to silence genes by targeting mRNA in mammalian cells.[29] Products +++++++++++ In 2016, Alnylam Pharmaceuticals had 18 potential treatments[30] in various development stages across three Strategic Therapeutic Areas (STArs), Genetic Medicine, Cardio-Metabolic Disease and Hepatic Infectious Disease. In 2016, the company had two candidates in phase III studies, patisiran, a treatment targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR), in patients with familial amyloidotic polyneuropathy (FAP) and revusiran, for the treatment of familial amyloidotic cardiomyopathy (FAC).[31] Alnylam off as development of key drug discontinued ++++++++++++++++++++++++++++++++++++++++++++++++++++ Wednesday, 5 Oct 2016 | 5:11 PM ET | 02:46 Alnylam Pharmaceuticals said on Wednesday it would halt development of an experimental therapy for a rare genetic condition that can cause heart failure, after a late-stage study showed that patients given the drug were more likely to die than patients treated with a placebo. Alnylam shares fell more than 48 percent following the announcement and ended the day at $36.21 a share. The drug, revusiran, was being developed for treating hereditary amyloidosis with cardiomyopathy, a condition in which amyloid plaque — similar to the substance found in the brains of Alzheimers' patients — collects in organs including the heart, where it can cause heart failure. Alnylam specializes in a technology known as RNA interference (RNAi), which prevents genes from making their designated proteins. Revusiran was designed to target the gene involved in producing the abnormal protein which causes amyloidosis. Amyloidosis is diagnosed in 6 to 10 Americans per million each year, according to the American Heart Association, though it is likely underdiagnosed. Alnylam said study safety monitors recommended that the Phase III trial be suspended after patients on a previous study developed neuropathy, or nerve pain. Unblinded data subsequently "revealed an imbalance of mortality in the revusiran arm as compared to placebo." The company said the decision does not affect its lead product patisiran, which is currently in Phase III development for treatment of amyloidosis with polyneuropathy, or any other Alnylam investigational RNAi therapeutic program. Alnylam also said current data across its other programs, including a cholesterol-lowering drug partnered with The Medicines, do not show evidence of drug-related neuropathy. Shares of The Medicines declined 8 percent to close at $35.33. Alnylam last month halted development of an earlier-stage RNAi compound after observing elevated liver enzymes in healthy volunteers.