Alnylam Pharmaceuticals presents data on RNAi therapeutic targeting PCSK9 for hypercholesterolemia

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today the presentation of new pre-clinical data from its hypercholesterolemia program, performed in collaboration with scientists at the University of Texas Southwestern Medical Center at Dallas. The data were presented at the PCSK9 Conference: From Gene to Therapeutics held in Nantes, France from March 11-13, 2010. Alnylam has an ongoing development program focused on using RNAi therapeutics targeting proprotein convertase subtilisin/kexin type 9, or PCSK9, as a novel strategy for reducing LDL (or “bad”) cholesterol. The new data demonstrated durable reductions of cholesterol levels in both rodents and non-human primates with an RNAi therapeutic targeting PCSK9 using second generation lipid nanoparticle (LNP) formulations. Further, data also showed the ability to utilize siRNA combination approaches to achieve efficient silencing of separate and distinct genes to achieve cholesterol lowering.

“We are very encouraged by the progress we have made in our development efforts for an RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia. With an RNAi approach, both intracellular and extracellular PCSK9 levels can be reduced, thereby replicating the human genetics”

“We are very encouraged by the progress we have made in our development efforts for an RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia. With an RNAi approach, both intracellular and extracellular PCSK9 levels can be reduced, thereby replicating the human genetics,” said Kevin Fitzgerald, Ph.D., Director of Research at Alnylam. “In addition to the markedly improved potency we demonstrated last year with second generation LNPs, we are now able to show that PCSK9 silencing effects are durable over a remarkably extended period of time. Further, these new data highlight our ability to investigate liver-specific silencing of target combinations in order to develop novel RNAi therapeutics for the treatment of hypercholesterolemia, as well as potentially other metabolic disorders.”

The new in vivo research findings presented at this meeting were performed using a systemically delivered RNAi therapeutic targeting PCSK9 and formulated in a second generation LNP, developed in collaboration with Tekmira Pharmaceuticals Corporation, The University of British Columbia, and AlCana Technologies, Inc. Data from these studies include:

• in vivo non-human primate data showing durable silencing of PCSK9 for more than 30 days following a single dose administration, with reduction in LDL cholesterol levels of approximately 50%;
• unlike results reported with monoclonal antibody strategies targeting extracellular PCSK9 (Chan et al., Proc. Natl. Acad. Sci. USA, 106(24): 9820-5, 2009), RNAi-mediated silencing of both intracellular and extracellular PCSK9 resulting in no lowering of HDL (or “healthy”) cholesterol;
• in vivo rodent data demonstrating the ability to utilize a novel dual-targeting approach to silence PCSK9 and a second undisclosed gene involved in lipid metabolism with a single RNAi therapeutic, resulting in a reduction in total cholesterol of greater than 40%; and,
• in vivo rodent data showing that injection of multiple siRNAs packaged in a single LNP formulation results in silencing of as many as 10 distinct target genes simultaneously.

“These new data continue to support the development of an RNAi therapeutic strategy of targeting PCSK9 for disease intervention in hypercholesterolemia,” said Jay Horton, M.D., Professor of Internal Medicine and Molecular Genetics, University of Texas Southwestern Medical Center. “Based on its novel mechanism and promising pre-clinical data observed to date, an RNAi therapeutic targeting PCSK9 has the potential to lower LDL cholesterol while preserving HDL cholesterol, and possibly function synergistically with statins for the treatment of hypercholesterolemia.”

Alnylam is developing ALN-PCS, an RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia; ALN-PCS is a systemically delivered RNAi therapeutic comprised of an optimized siRNA encapsulated in a second generation LNP formulation. Alnylam expects to advance its ALN-PCS program toward the clinic with a goal of initiating a Phase I clinical trial in 2011.