Genzyme is paying Alnylam $22.5 million up front as part of an exclusive alliance to develop and commercialize transthyretin (TTR)-targeting RNAi therapeutics for the treatment of transthyretin-mediated amyloidosis (ATTR) in Japan and other Asia-Pacific territories. Alnylam aims to continue its own development and commercialization of ALN-TTR in the U.S., Europe, and globally.

ATTR is a hereditary disease that is endemic in Japan. The condition causes nervous system and heart damage, and generally leads to death at between five and 15 years. Japanese patients often carry a specific TTR mutation known as V30M, which leads to a severe form of ATTR known as familial amyloidotic polyneuropathy (FAP). Mutations in TTR cause abnormal amyloid proteins to accumulate in and damage body organs and tissues, including peripheral nerves and heart, which causes intractable peripheral sensory neuropathy, autonomic neuropathy, and/or cardiomyopathy.

Genzyme and Alnylam will focus on developing the latter’s ALN-TTR program for FAP and other ATTR indications, including familial amyloidotic cardiomyopathy (FAC) and senile systemic amyloidosis (SSA). Under terms of the agreement Alnylam will be eligible for development milestone payments, and future royalties on sales of resulting therapeutics by Genzyme in its designated countries. The firms will shoulder their own development and commercialization activities in their respective territories.

Alnylam’s ALN-TTR portfolio is headed by ALN-TTR02, which is in a Phase II clinical trial, and ALN-TTRsc, a subcutaneously administered RNAi therapeutic in late-stage preclinical development. In July the firm reported positive data from a Phase I study with ALN-TTR02 in the treatment of ATTR. The results showed that therapy led to a 94% reduction in serum TTR protein levels, even when administered just once a month. With a Phase II trial ongoing, the firm projects starting a pivotal study in 2013.

The alliance with Genzyme is part of Alnylam 5×15 strategy, launched in January 2011, which provides a pathway for developing and commercializing RNAi therapeutics against genetically defined diseases with high unmet medical need. The firm aims to have five such RNAi therapeutic programs in clinical development by the end of 2015 including both in-house and partnered programs. Key programs include ALN-TTR, ALN-APC for the treatment of hemophilia, ALN-PCS for the treatment of severe hypercholesterolemia, ALN-HPN for the treatment of refractory anemia, and ALN-TMP for the treatment of hemoglobinopathies. 

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