Alnylam's Givosiran Looks Positive Overall in Phase III Trial for Rare Disease

Despite releasing positive data on its Phase III ENVISION trial, Alnylam Pharmaceuticals stock dropped 7.5 percent. Although not completely clear why the drop may be related to a high percentage of serious adverse events observed in the trial. The ENVISION Phase III trial evaluated givosiran, an investigational RNAi therapeutic that targets aminolevulinic acid synthase 1 (ALAS1) for the treatment of acute hepatic porphyria (AHP). AHP is a family of rare, genetic diseases characterized by possibly life-threatening attacks and for some, chronic debilitating symptoms. AHP is made up of four subtypes, each caused by a genetic defect that leads to a deficiency in one of the enzymes in the heme biosynthesis pathway in the liver. They all cause the accumulation of neurotoxic heme intermediates aminolevulinic acid (ALA) and porphobilinogen (PBG). ALA is believed to be the primary neurotoxic intermediate responsible for the symptoms. The trial met its primary endpoint, reduction in the annualized rate of composite porphyria attacks compared to placebo. It also hit statistically significant results for five of nine secondary endpoints. Alnylam called the drug’s safety and tolerability profile “encouraging, especially in this high unmet disease.”