Tekmira Pharmaceuticals Initiates ApoB SNALP Phase 1 Clinical Trial

Main Category: Cholesterol
Also Included In: Clinical Trials / Drug Trials
Article Date: 05 Jul 2009 - 0:00 PDT

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Tekmira Pharmaceuticals Corporation (TSX:TKM) announced that it has initiated a Phase 1 human clinical trial for ApoB SNALP. ApoB SNALP, Tekmira's lead RNAi therapeutic product candidate, is being developed as a treatment for patients with elevated low-density lipoprotein (LDL) cholesterol, or "bad" cholesterol, who are not well served by current therapy. ApoB SNALP is designed to reduce the production of apolipoprotein B (ApoB), a protein produced in the liver that plays a central role in cholesterol metabolism.

Dr. Mark J. Murray, Tekmira's President and CEO, said "We are very excited to initiate the ApoB SNALP Phase 1 clinical trial representing our first RNAi therapeutic clinical trial and an important milestone for Tekmira. Our preclinical data package supports ApoB as an excellent target for LDL cholesterol lowering and we believe ApoB SNALP is the most advanced RNAi therapeutic targeting a metabolic condition. We expect to complete the Phase 1 clinical trial in early 2010."

The Phase 1 clinical trial will evaluate the safety, tolerability and pharmacokinetics of escalating single doses of ApoB SNALP in approximately 30 patients with elevated LDL cholesterol. Each dosing cohort will include four patients; three patients will receive ApoB SNALP and one patient will receive a placebo. The trial is also designed to provide preliminary data on the ability of ApoB SNALP to lower serum LDL cholesterol levels. Patients whose LDL cholesterol is reduced by greater than 15% from baseline will be followed until their LDL cholesterol levels return to baseline.

Tekmira's therapeutic approach is to target ApoB, a protein synthesized in the liver that is essential to the assembly and secretion of very low density lipoprotein (VLDL), a precursor to LDL, both of which are required for the transport and metabolism of cholesterol. ApoB SNALP consists of small interfering RNA (siRNA), designed to silence ApoB, encapsulated in a SNALP formulation. ApoB SNALP is delivered with high efficiency into the liver hepatocytes, the cells which produce ApoB, where the siRNA acts to silence the mRNA coding for ApoB protein resulting in a decrease in circulating VLDL and LDL.

The therapeutic activity of ApoB SNALP has been demonstrated in preclinical models of high cholesterol. Rodents fed a high fat diet demonstrate a 50-100% increase in total cholesterol in the blood. A single ApoB SNALP treatment can overcome such diet-induced high cholesterol, returning blood cholesterol levels to normal. The suppressive effects of a single ApoB SNALP dose lasts for several weeks in preclinical models of high cholesterol.

About RNAi and SNALP

RNAi drugs have the potential to treat human diseases by "switching-off" disease causing genes. The technology, representing one of the most promising and rapidly advancing frontiers in biology and drug discovery, was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi drugs, such as siRNA, require delivery technology to be administered systemically. In preclinical studies, Tekmira's SNALP (stable nucleic acid-lipid particles) technology has been shown to be a safe and effective way to deliver RNAi drugs to disease sites. Tekmira believes it has a leading intellectual property position in the field of siRNA delivery.

Source
Tekmira Pharmaceuticals Corporation