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Alnylam Adds Hepatic Porphyria Drug to Official Pipeline


Alnylam Pharmaceuticals said this week that it has formally advanced its preclinical hepatic porphyria treatment into its development pipeline.

The drug, called ALN-AS1, is designed to silence ALAS-1, a liver-expressed rate-limiting enzyme upstream of porphobilinogen deaminase. Inhibition of ALAS-1 has been shown to reduce the accumulation of heme precursors that cause the clinical manifestations of acute intermittent porphyria — a form of porphyria Alnylam is focusing on.

The company said that non-human primate data show that multiple subcutaneous doses of a GalNAc conjugate formulation of the drug led to rapid, dose-dependent, and long-lasting knockdown of the ALAS-1 mRNA, with an ED50 of approximately 1.25 mg/kg.

In rodent studies, doses as low as 2.5 mg/kg resulted in a complete blunting of phenobarbital-induced over-production of the toxic heme intermediates PBG and ALA.

Alnylam said that it will now begin investigational new drug application-enabling studies of ALN-AS1, with the goal of filing an IND next year.