Alnylam Advances ALAS-1 Attacker

Alnylam Pharmaceuticals will advance its development candidate for ALN-AS1, an RNAi therapeutic targeting aminolevulinate synthase-1 (ALAS-1) for the treatment of hepatic porphyrias including acute intermittent porphyria (AIP).

A preclinical study showed that subcutaneous administration of a GalNAc-siRNA targeting ALAS-1 led to rapid, dose-dependent, and long-lasting knockdown of ALAS-1 mRNA and complete inhibition of the toxic intermediates that mediate the symptoms and pathology of AIP. Based on these findings, including results in non-human primate studies, the company has selected its ALN-AS1 Development Candidate and expects to file an Investigational New Drug (IND) application for this RNAi therapeutic in 2014.

Hepatic porphyrias, including AIP, are ultra-rare orphan diseases caused by loss-of-function mutations in enzymes involved in heme biosynthesis, leading to accumulation of toxic heme intermediate precursors. In the case of AIP, there are approximately 5,000 patients in the U.S. and Europe that suffer acute, life-threatening porphyria attacks every year; there are approximately 500 patients afflicted with recurrent debilitating attacks, often occurring once per month. Treatment options for AIP patients suffering from an attack are limited, and include the use of heme preparations that show limited efficacy and are associated with a number of complications. Currently, there are no drugs available to prevent attacks from occurring.