Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today the presentation of new pre-clinical data on RNAi therapeutics targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR). These data were presented at the International Symposium on Amyloidosis (ISA) held April 27 – May 1, 2014 in Indianapolis, Indiana. In a poster titled “ Preclinical Evaluation of RNAi Therapeutics for the Treatment of ATTR: An Update,” Alnylam scientists presented data confirming that the degree of TTR knockdown in a mouse disease model was highly correlated with regression of TTR tissue deposits. Further, comparative studies were performed with the TTR stabilizer tafamidis and a TTR-specific antisense oligonucleotide (ASO). In these pre-clinical studies, RNAi therapeutics targeting TTR were shown to have superior pharmacologic profiles.
“We believe that these new pre-clinical data highlight the potential for RNAi therapeutics targeting TTR to emerge as the optimal approach for the treatment of ATTR. First, in a mouse model of ATTR, we’ve demonstrated that the degree of TTR suppression at steady state knockdown is highly correlated with regression of TTR deposits in multiple tissues. These data suggest that the 80% TTR knockdown target level achieved with patisiran and ALN-TTRsc could facilitate a reduced pathogenic accumulation of TTR amyloid and possibly even a regression of TTR amyloid in patients with ATTR,” said Rachel Meyers, Ph.D., Vice President, Research and RNAi Lead Development at Alnylam. “Moreover, our scientists and collaborators presented comparative studies of RNAi therapeutics with a TTR stabilizer and an antisense oligonucleotide (ASO). In a mouse model of ATTR, treatment with the TTR stabilizer tafamidis resulted in a trend for regression of TTR deposits in a limited number of tissues, while administration of an RNAi therapeutic led to a statistically significant regression in all tissues evaluated. Additional comparative studies were performed with a TTR-specific ASO and showed that RNAi therapeutics achieve a more rapid, potent, and robust knockdown of TTR than the ASO, with an over 100-fold lower drug exposure in liver and ‘bystander’ tissues such as kidney. We believe that the ability of RNAi therapeutics to achieve potent TTR knockdown with lower tissue exposure could result in a more favorable efficacy and tolerability profile.”