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Alnylam Submits CTA for Lipid Nanoparticle-Based RNAi TTR, ALN-TTR02

Alnylam Pharmaceuticals, a company specializing in RNAi therapeutics, has announced the submission of a clinical trial application (CTA) with the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) to start a Phase I clinical study of its RNAi therapeutic targeting transthyretin (TTR) called ALN-TTR02 for treating TTR-mediated amyloidosis (ATTR).

ALN-TTR02 is a systemically transported RNAi therapeutic comprising a siRNA formulation using a second-generation lipid nanoparticle technology. Alnylam Pharmaceuticals anticipates starting the ALN-TTR02 Phase I study during the first half of the fiscal year 2012 after obtaining the CTA clearance. The data is intended to be reported during the third quarter of this year.

TTR gene mutations are the cause of the autosomal-dominant inherited disease ATTR. Pre-clinical studies have demonstrated that TTR silencing by ALN-TTR02 was 10 times better than that of ALN-TTR01 comprising a siRNA formulated using a first-generation lipid nanoparticle technology.

According to the CTA filing, ALN-TTR02’s Phase I clinical study is indented to be carried out with 32 healthy volunteers in the United Kingdom as a single-ascending, single-blend and randomized dose study. To assess the tolerability and safety of ALN-TTR02’s single dose is the main objective of the trial. Evaluation of clinical activity of ALN-TTR02 in terms of TTR levels and pharmacokinetic characterization of the drug are the secondary objectives of the study.

Alnylam Pharmaceuticals’ Senior Vice President and Chief Medical Officer, Akshay Vaishnaw stated that the company also plans to start a Phase II clinical trial of ALN-TTR02 in patients suffering from familial amyloidotic polyneuropathy during the second half of 2012, with pivotal trials of ALN-TTR02 scheduled to be started in 2013.

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