Phase 2, open-label extension (OLE) study of revusiran, an investigational RNAi therapeutic for the treatment of patients with transthyretin cardiac amyloidosis

Background In transthyretin (TTR) cardiac amyloidosis, myocardial deposition and accumulation of liver-derived TTR fibrils results in heart failure and death. The hereditary form of the disease is caused by mutations in the TTR gene and presents as familial amyloidotic cardiomyopathy (FAC), whereas senile systemic amyloidosis (SSA) is an acquired disease caused by wild-type TTR. There are currently no approved therapies available for ATTR cardiac amyloidosis. Revusiran is a liver-directed subcutaneously administered investigational RNA interference therapeutic comprised of a GalNAc-siRNA conjugate targeting both mutant and wild-type TTR mRNA. A Ph 2 study of revusiran in 26 patients with ATTR cardiac amyloidosis, in which revusiran was generally well tolerated and associated with > 85% sustained knockdown of serum TTR, was recently completed. A Ph 2 open label extension (OLE) of revusiran, available to all patients who participated in the Ph 2 trial, was initiated in November 2014.