Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY) and Genzyme, a Sanofi company (EURONEXT: SAN and NYSE: SNY), announced today that they have formed an exclusive alliance to develop and commercialize RNAi therapeutics targeting transthyretin (TTR) for the treatment of transthyretin-mediated amyloidosis (ATTR) in Japan and other Asia-Pacific countries. ATTR is a rare, debilitating, hereditary disease that damages the nervous system and heart, resulting in a life expectancy of 5 to 15 years.
"Our ALN-TTR program holds promise as a breakthrough therapy for the treatment of ATTR, a debilitating orphan disease. As the lead program in our 'Alnylam 5x15' product strategy, we also view this program as a key part of building Alnylam for the future," said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. "In this important collaboration, Genzyme will advance our ALN-TTR program with their proven capabilities in the Japanese and broader Asian market, while we maintain our plans to develop and commercialize this potential breakthrough medicine in the U.S., Europe, and rest of world. In addition, a key part of the value proposition in this alliance for Alnylam is the potential for significant royalty payments on sales of products."
ATTR is an endemic disease in Japan, with a significant number of patients carrying the V30M TTR mutation which leads to onset of a severe form of ATTR known as familial amyloidotic polyneuropathy (FAP). Together, Alnylam and Genzyme intend to maximize the value of ALN-TTR worldwide by developing the program in FAP and other ATTR indications, such as familial amyloidotic cardiomyopathy (FAC) and senile systemic amyloidosis (SSA). Alnylam's ALN-TTR program currently includes ALN-TTR02, which is in a Phase II clinical trial, and ALN-TTRsc, a subcutaneously administered RNAi therapeutic in late stage pre-clinical development.
Under the terms of the agreement, Genzyme will make an upfront cash payment of $22.5 million to Alnylam. The agreement also includes development milestone payments and tiered royalties expected to yield an effective rate in the mid-teens to mid-twenties on Genzyme's sales of ALN-TTR products in their territory. In addition, each party will be responsible for the development and commercialization activities in their respective territories.
"We are encouraged by Alnylam's progress with their ALN-TTR program and are excited by the potential for this innovative drug candidate to make a difference in the lives of patients with ATTR. The results to date demonstrate impressive clinical activity and support advancement of this promising therapeutic into pivotal studies and toward the market," said David Meeker, M.D., President and Chief Executive Officer of Genzyme. "As we work to build our pipeline through both internal research and development, and through external collaborations, we look forward to working with Alnylam on this important program."
Recently, Alnylam presented positive clinical results from its ALN-TTR02 Phase I trial demonstrating robust and unprecedented knockdown of serum TTR protein levels of up to 94%; the overall results were highly significant (p<0.00001 by ANOVA). Suppression of TTR, the disease-causing protein in ATTR, was found to be rapid, dose dependent, durable, and specific after just a single dose. The drug was generally safe and well tolerated in this Phase I study. Alnylam is currently enrolling patients in a Phase II multi-dose study of ALN-TTR02 in ATTR patients and aims to initiate a Phase III pivotal study of ALN-TTR02 by the end of 2013.