Alnylam reported positive results from a Phase I trial with ALN-TTRsc in 28 healthy volunteers at the Heart Failure Society of America 17th Annual Scientific Meeting held in September 2013. The results of the clinical study showed that ALN-TTRsc administration led to robust, consistent, and statistically significant (p<0.01) knockdown of serum TTR of up to 94%. Knockdown of TTR was found to be rapid, dose-dependent, and durable. ALN-TTRsc was found to be generally safe and well tolerated in the study. Importantly, these human study results were the first to be reported for Alnylam’s proprietary GalNAc-siRNA conjugate delivery platform, enabling subcutaneous dosing of RNAi therapeutics with a wide therapeutic index.
In 2012, Alnylam entered into an exclusive alliance with Genzyme, a Sanofi company, to develop and commercialize RNAi therapeutics, including patisiran 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.
About Transthyretin-Mediated Amyloidosis
Transthyretin (TTR)-mediated amyloidosis (ATTR) is an inherited, progressively debilitating, and fatal disease caused by mutations in the TTR gene. TTR protein is produced primarily in the liver and is normally a carrier for retinol binding protein. Mutations in TTR cause abnormal amyloid proteins to accumulate and damage body organs and tissue, such as the peripheral nerves and heart, resulting in intractable peripheral sensory neuropathy, autonomic neuropathy, and/or cardiomyopathy. ATTR represents a major unmet medical need with significant morbidity and mortality; familial amyloidotic polyneuropathy (FAP) affects approximately 10,000 people worldwide and familial amyloidotic cardiomyopathy (FAC) affects at least 40,000 people worldwide. FAP patients have a life expectancy of five to 15 years from symptom onset, and the only approved treatment options for early stage disease are liver transplantation, and tafamidis (approved in Europe). The mean survival for FAC patients is approximately 2.5 years, and there are no approved therapies. Senile systemic amyloidosis (SSA) is a non-hereditary form of TTR cardiac amyloidosis caused by idiopathic deposition of wild-type TTR; its prevalence is generally unknown, but is associated with advanced age. There is a significant need for novel therapeutics to treat patients with TTR amyloid polyneuropathy and/or cardiomyopathy.