Alnylam Pharmaceuticals initiates dosing in Phase I human clinical study with ALN-TTR01

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today it has initiated dosing in a Phase I human clinical study with ALN-TTR01. The study is aimed at evaluating the safety and tolerability of ALN-TTR01 in patients with transthyretin (TTR)-mediated amyloidosis (ATTR), and is also designed to provide preliminary data on human proof of concept based on measurements of TTR serum levels. ALN-TTR01 is a systemically delivered RNAi therapeutic being developed for the treatment of ATTR, including familial amyloidotic polyneuropathy (FAP) and familial amyloidotic cardiomyopathy (FAC).

“RNAi therapeutics represent a novel and exciting approach for the treatment of ATTR. Indeed, based on our understanding of the human genetics of this disease, this novel modality provides an encouraging therapeutic strategy”

"We are very excited about the potential for our ALN-TTR program to make a significant impact in the treatment of this disease," said Akshay Vaishnaw, M.D., Ph.D., Senior Vice President, Clinical Research at Alnylam. "Our pre-clinical data in this program are very encouraging and point to the potential for significant clinical impact. As reported earlier, the primary objective of this current Phase I study is to demonstrate safety and tolerability of ALN-TTR01 in ATTR patients. In addition, we also believe we have an opportunity to assess preliminary human proof of concept based on measurements of serum TTR levels in patient samples."

ATTR is caused by mutations in the TTR gene, which is expressed predominantly in the liver, and results in the accumulation of pathogenic deposits of mutant and wild-type TTR protein in multiple extra-hepatic tissues, including the peripheral nervous system, heart, and the gastrointestinal tract. Pre-clinical studies in a mouse transgenic model have shown that treatment with ALN-TTR01 results in both prevention and regression of pathogenic TTR deposits in peripheral tissues including dorsal root ganglia, sciatic nerve, stomach, and intestines. Further, ALN-TTR01 administration in non-human primates was found to result in dose-dependent and durable, yet reversible silencing of the TTR gene and serum levels of TTR.

The Phase I trial is being conducted in Portugal, Sweden, and the U.K., and is a randomized, blinded, placebo-controlled dose escalation study designed to enroll approximately 28 ATTR patients. The primary objective is to evaluate the safety and tolerability of a single dose of intravenous ALN-TTR01, with patients being enrolled into five sequential cohorts of increasing doses ranging from 0.01 to 0.4 mg/kg. Secondary objectives include characterization of plasma and urine pharmacokinetics of ALN-TTR01 and assessment of pharmacodynamic activity based on measurements of circulating TTR serum levels.

"RNAi therapeutics represent a novel and exciting approach for the treatment of ATTR. Indeed, based on our understanding of the human genetics of this disease, this novel modality provides an encouraging therapeutic strategy," said Teresa Coelho, M.D., Director, Unidade Clinica de Paramiloidose. Based in Porto, Portugal where she treats several hundred patients with the disease, Dr. Coelho is an internationally renowned expert in ATTR. She added, "The pre-clinical data with ALN-TTR01 obtained to date are promising, especially recent results showing regression of pathogenic TTR tissue deposition in the mouse transgenic model. By all accounts, I am excited about the translation of this new agent into clinical trials as there are currently few options for patients suffering from this disease."

ALN-TTR01 is in clinical development using stable nucleic acid-lipid particles (SNALP) delivery technology developed in collaboration with Tekmira Pharmaceuticals Corporation.