Alnylam Pharmaceuticals Inc (ALNY)

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8:03AM Alnylam Pharma collaborators publish new pre-clinical results with an RNAi therapeutic approach for inducing endogenous erythropoiesis for the treatment of anemia (ALNY) 11.02 : Co announced the publication of new pre-clinical results in the journal Blood that describe targeting the egg-laying nine homolog (EglN) pathway for the treatment of anemia using RNAi therapeutics. The new findings show that activation of hepatic erythropoietin production using systemically delivered siRNA targeting EglN prolyl hydroxylases leads to improved red blood cell production in pre-clinical models of anemia. New approaches that induce endogenous mechanisms for erythropoiesis could address unmet medical needs in the management of anemia in patients who are refractive to current therapies. Specifically, data showed that a systemically administrated RNAi therapeutic targeting the EglN family of proteins achieved dose-dependent silencing of EglN genes in vivo in animal models. The research showed that EglN silencing resulted in sustained increase in circulating erythropoietin that was generated specifically by the liver. The induction of endogenous liver erythropoietin expression recapitulates a developmental pathway for red blood cell production known to exist in the fetus. This increase in erythropoietin was detectable out to two weeks after administration of a single dose of the RNAi therapeutic and was associated with a sustained increased in red blood cell parameters including reticulocyte count, hemoglobin and hematocrit. Further, RNAi therapeutics targeting the EglN pathway were found to significantly correct anemia in models of both renal failure and chronic inflammation. Other changes observed with RNAi therapeutic targeting EglNs, such as decreased production of hepcidin, were also demonstrated and could enhance the effectiveness of endogenous erythropoiesis by improving iron mobilization, thereby lowering the circulating erythropoietin levels needed to promote red blood cell production