Alnylam files CTA with the U.K. MHRA to initiate ALN-TTR02 Phase I trial in ATTR

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it has filed a Clinical Trial Application (CTA) with the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) to initiate a Phase I clinical trial with ALN-TTR02, an RNAi therapeutic targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR). ALN-TTR02 is a systemically delivered RNAi therapeutic, targeting the TTR gene, that comprises an siRNA formulated in a second-generation lipid nanoparticle (LNP). Following clearance of the CTA, Alnylam expects to initiate the ALN-TTR02 Phase I study in the first half of 2012 with data expected to be reported in the third quarter of 2012.

"We are very committed to the continued advancement of our ALN-TTR program, which we believe has the potential to emerge as the leading innovative medicine for the treatment of ATTR. Indeed, our preliminary ALN-TTR01 trial results showed rapid and durable lowering of TTR serum levels in ATTR patients with just a single dose; we can confidently expect even more robust results with ALN-TTR02 which utilizes our second-generation lipid nanoparticle delivery platform," said Akshay Vaishnaw, M.D., Ph.D., Senior Vice President and Chief Medical Officer of Alnylam. "To put this new program into context, pre-clinical studies have shown that administration of ALN-TTR02 results in a greater than 10-fold improvement in TTR silencing as compared with ALN-TTR01. Moreover, our recent preliminary clinical results with ALN-PCS, utilizing the same second-generation LNP formulation as ALN-TTR02, demonstrated initial safety and robust potency with greater than 65% silencing of the protein target, PCSK9, at the current dose level. Accordingly, we very much look forward to the continued advancement of ALN-TTR02, including the start of this Phase I clinical trial in healthy volunteers in the first half of this year and data in the third quarter. We also expect to initiate a Phase II study with ALN-TTR02 in familial amyloidotic polyneuropathy, or FAP, patients in the second half of this year with the start of pivotal trials with ALN-TTR02 in 2013."

ATTR is an autosomal dominant inherited disease 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, gastrointestinal tract, and heart. Alnylam recently presented preliminary results from its Phase I study of ALN-TTR01, which utilizes the identical siRNA as in ALN-TTR02 but formulated in a first-generation LNP. Preliminary data from this study showed that administration of ALN-TTR01 resulted in statistically significant reductions in serum TTR protein levels in ATTR patients with a mean reduction of 41% relative to placebo.

"RNAi therapeutics represent a novel and compelling approach for the treatment of ATTR. Based on our understanding of the pathogenesis of this disease, TTR lowering defines an encouraging therapeutic strategy," said Philip Hawkins, FMedSci., Professor of Medicine, University College London Medical School. "The recent preliminary clinical data for ALN-TTR01 in patients are very promising and I am excited about the translation of this second-generation agent in clinical trials, as there are currently few options for patients suffering from this disease."


Alnylam Pharmaceuticals, Inc.


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