Alnylam begins dosing in Phase I clinical trial with ALN-TTRsc for treatment of ATTR

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it has initiated dosing in its Phase I clinical trial with ALN-TTRsc, an RNAi therapeutic targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR). ATTR is caused by mutations in the TTR gene which cause abnormal amyloid protein deposits to accumulate in various tissues including peripheral nerves and heart, resulting in 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. 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.

“ATTR is a genetic disease with significant unmet medical need and limited treatment options for patients. RNAi therapeutics are a novel and compelling approach for the treatment of ATTR, as this novel modality has been shown to achieve robust knockdown of serum levels of both wild-type and mutant TTR”

"RNAi therapeutics hold great promise for the treatment of ATTR since they have demonstrated rapid, potent, and durable knockdown of TTR, the disease-causing protein. We are advancing what we believe to be the industry leading effort in ATTR; this includes ALN-TTRsc for the treatment of FAC and ALN-TTR02 for the treatment of FAP which is currently enrolling patients in a Phase II trial," said Akshay Vaishnaw, M.D., Ph.D., Executive Vice President and Chief Medical Officer of Alnylam. "The start of this Phase I trial with ALN-TTRsc represents the first for an RNAi therapeutic that utilizes our proprietary GalNAc conjugate delivery platform. It also marks the first subcutaneously delivered, systemic RNAi therapeutic for the industry. We look forward to the continued advancement of ALN-TTRsc for the treatment of FAC."

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. Secondary objectives include assessment of clinical activity of the drug as measured by serum TTR levels. Alnylam expects to present data from this trial in mid-2013. Upon completion of the Phase I trial, the company plans to start a Phase II clinical study of ALN-TTRsc in FAC patients by the end of 2013 and, assuming positive results, expects to start a pivotal trial for ALN-TTRsc in FAC patients in 2014.

"ATTR is a genetic disease with significant unmet medical need and limited treatment options for patients. RNAi therapeutics are a novel and compelling approach for the treatment of ATTR, as this novel modality has been shown to achieve robust knockdown of serum levels of both wild-type and mutant TTR," said Philip Hawkins, FMedSci., Professor of Medicine, University College London Medical School. "I am encouraged by the clinical and pre-clinical data to date with Alnylam's ALN-TTR program and look forward to the continued advancement of this effort for patients suffering from either the cardiomyopathy or polyneuropathy manifestations of this devastating disease."

ATTR is an autosomal dominant inherited disease caused by mutations in the TTR gene, which is expressed predominantly in the liver. Pre-clinical studies have shown that subcutaneous administration of ALN-TTRsc resulted in potent and sustained suppression of TTR. In non-human primates, ALN-TTRsc administration resulted in an approximately 80% reduction of TTR at doses as low as 2.5 mg/kg. In single- and multi-dose pre-clinical safety studies in rodents and non-human primates, ALN-TTRsc was found to be generally safe and well tolerated. Specifically, at doses as high as 300 mg/kg in non-human primates, ALN-TTRsc was well tolerated with no clinical signs, no adverse laboratory or histopathologic findings, no elevations in cytokines or complement, and no significant injection site reactions.

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.

Source: Alnylam Pharmaceuticals