7:02AM Alnylam Pharma reports positive clinical results -- with up to 94% knockdown of serum transthyretin -- for ALN-TTRsc; Multiple doses of aln-ttrsc found to be generally safe and well tolerated in phase I study (ALNY) 57.25 : Key Points:
ALN-TTRsc clinical activity establishes new benchmark for consistent ttr knockdown of ~90%.
Multiple doses of aln-ttrsc found to be generally safe and well tolerated in phase i study.
Results Establish human translation of Alnylam's proprietary galnac-sirna conjugate platform for subcutaneous administration of RNAi Therapeutics with wide therapeutic index
Company to host conference call at 8:00 a.m. today to discuss clinical results.
Co announced positive interim results from its Phase I clinical trial of ALN-TTRsc, a subcutaneously delivered RNAi therapeutic targeting the transthyretin gene for the treatment of TTR-mediated amyloidosis. The data are being presented today at the Heart Failure Society of America 17th Annual Scientific Meeting being held September 22 -- 25, 2013 in Orlando, Fla. Results show that ALN-TTRsc administration led to robust, consistent, and statistically significant knockdown of serum TTR protein levels of up to 94%. In addition, knockdown of TTR, the disease causing protein in ATTR, was found to be rapid, dose dependent, and durable. To date, ALN-TTRsc has been found to be generally safe and well tolerated in this study.
In addition, knockdown of TTR, the disease causing protein in ATTR, was found to be rapid, dose dependent, and durable. To date, ALN-TTRsc has been found to be generally safe and well tolerated in this study. These human data are the first to be presented for Alnylam's proprietary GalNAc-siRNA conjugate delivery platform, enabling subcutaneous dosing of RNAi therapeutics with a wide therapeutic index, and demonstrate human translation for this platform. Moreover, these results establish a new benchmark for consistent TTR knockdown of approximately 90% for RNA therapeutics in development for the treatment of ATTR.
ALN-TTRsc, which is being developed for the treatment of FAC, is a subcutaneously administered RNAi therapeutic that comprises an siRNA conjugated to a GalNAc ligand that enables receptor-mediated delivery to the liver. ALN-TTRsc is the first GalNAc-siRNA -- and the first subcutaneously delivered systemic RNAi therapeutic -- to enter clinical development stages. Alnylam is also developing ALN-TTR02, an intravenously administered RNAi therapeutic targeting TTR for the treatment of ATTR patients with FAP.
The Phase I trial of ALN-TTRsc is being conducted in the U.K. as a randomized, double-blind, placebo-controlled, single- and multi-dose, dose-escalation study, enrolling up to 40 healthy volunteer subjects. The primary objective of the study is to evaluate the safety and tolerability of single and multiple doses of subcutaneously administered ALN-TTRsc.
Interim data from the 28 subjects enrolled and analyzed in this study to date showed that single- and multi-dose administration of ALN-TTRsc resulted in rapid, dose-dependent, consistent, and durable knockdown of serum TTR levels. In the multi-dose cohorts, there was a statistically significant knockdown of serum TTR at doses of 2.5 mg/kg, 5.0 mg/kg, and 10.0 mg/kg as compared to placebo.
In 2012, Alnylam entered into an exclusive alliance with Genzyme, a Sanofi company, to develop and commercialize RNAi therapeutics, including ALN-TTR02 and ALN-TTRsc, for the treatment of ATTR in Japan and the broader Asian-Pacific region. Alnylam plans to develop and commercialize the ALN-TTR program in North and South America, Europe, and rest of the world.
