Tekmira Pharmaceuticals Corporation (TSX: TKM) announced today that its Investigational New Drug (IND) application for ApoB SNALP has been cleared by the United States Food and Drug Administration (FDA) allowing Tekmira to begin enrolling patients in a Phase 1 human clinical trial. 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. 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 "The successful FDA review of our ApoB SNALP IND is a testament to the scientific quality of our IND submission. We remain on track to achieve our milestone of initiating a Phase 1 clinical trial before mid-year in patients with high cholesterol."
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. The trial is also designed to provide preliminary data on the ability of ApoB SNALP to lower serum LDL cholesterol levels. Phase 1 data is expected to be available late 2009 or early 2010.
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.