Alnylam Pharmaceuticals, Inc., a leading RNAi therapeutics company, has initiated a pilot phase II study with ALN-TTRsc, a subcutaneously delivered RNAi therapeutic targeting the transthyretin (TTR) gene in development for the treatment of TTR-mediated amyloidosis (ATTR). The phase II trial, which is now open for enrollment, is aimed at evaluating the tolerability and preliminary clinical activity of ALN-TTRsc in TTR cardiac amyloidosis patients with familial amyloidotic cardiomyopathy (FAC) – which is caused by autosomal dominant mutations in the TTR gene, or senile systemic amyloidosis (SSA) – which is caused by idiopathic accumulation of wild-type TTR in the heart.

The company expects to present data from the phase II trial in late 2014, and assuming positive results, begin a phase III trial in TTR cardiac amyloidosis patients by the end of 2014.

“Our recently presented phase I study results of ALN-TTRsc demonstrated robust, up to 94 per cent knockdown of serum TTR, which we believe provide an encouraging profile of clinical activity that warrants further advancement of this drug candidate for the treatment of TTR cardiac amyloidosis. We are pleased to announce that we have initiated our pilot phase II trial with ALN-TTRsc, with the study now open for enrollment. Initiation of this phase II trial highlights continued execution on our ‘Alnylam 5x15’ product development and commercialization strategy, which is focused on advancing RNAi therapeutics toward genetically defined targets for the treatment of diseases with high unmet medical need,” said Akshay Vaishnaw, MD, Ph.D., executive vice president and chief medical officer of Alnylam. “This new study aims to evaluate the tolerability and preliminary clinical activity of ALN-TTRsc in patients with TTR cardiac amyloidosis. Since ALN-TTRsc achieves robust knockdown of serum TTR, the disease-causing protein in ATTR, we believe that this investigational agent has encouraging potential as a new therapeutic option for patients. Further, it is notable that ALN-TTRsc is the most advanced program in our pipeline that utilizes our GalNAc-conjugate approach for subcutaneous delivery of RNAi therapeutics, and the first to enter phase II trials; as such, we are pleased with this important industry milestone with the continued development of RNAi therapeutics that utilize this delivery approach in clinical studies.”

ATTR is caused by mutations in the TTR gene which cause abnormal TTR amyloid protein deposits to accumulate in various tissues including peripheral nerves and heart, resulting in neuropathy and/or cardiomyopathy.

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.