8:01AM Alnylam Pharma presents key pre-clinical proof-of-concept data for ALN-AS1; RNAi therapeutics targeting ALAS-1 completely block production of toxic heme biosynthesis intermediates that cause symptoms and disease pathology (ALNY) 27.21 : Co announced that it has presented key pre-clinical proof-of-concept data from its RNAi therapeutic program targeting aminolevulinate synthase-1 (ALAS-1) for the treatment of porphyria including acute intermittent porphyria. Specifically, Alnylam scientists and collaborators at the Icahn School of Medicine at Mount Sinai in New York City presented data from pre-clinical models of the human disease showing that RNAi therapeutics targeting ALAS-1 can completely block the abnormal production of toxic intermediates of the heme biosynthesis pathway that cause the symptoms and disease pathology of AIP. Alnylam's AIP drug candidate, ALN-AS1, is part of the co's "Alnylam 5x15" product development and commercialization strategy, in which the co aims to advance five genetic disease target programs into clinical development, including programs in late stages, by the end of 2015.
Prophylactic administration of an ALAS-1 specific siRNA completely protected mice from phenobarbital-induced up-regulation of hepatic ALAS-1 mRNA and the resulting accumulation of the neurotoxic ALA and PBG heme biosynthesis precursors. This protective effect was dose responsive and durable, with a single dose administration resulting in a protective effect that lasted for at least two weeks. Further, in a treatment model, a single dose of ALAS-1 siRNA rapidly reduced the high levels of plasma ALA and PBG that were elevated during a phenobarbital-induced acute attack. Further, preliminary comparative studies show that ALAS-1 siRNA administration was more effective than heme administration in the treatment of an acute attack. Finally, the company presented results from its ongoing GalNAc-siRNA conjugate efforts enabling subcutaneous dose administration. In particular, a prototype GalNAc-siRNA targeting ALAS-1 was shown to be effective in blocking ALA and PBG production in both prophylactic and treatment models of AIP. The company is on track to designate a GalNAc-siRNA development candidate, ALN-AS1, in late 2013 resulting in an IND filing in 2014.
