Tekmira Pharmaceuticals Corporation, a leading developer of RNA interference (RNAi) therapeutics, along with its collaborators at the United States National Cancer Institute (NCI), announced that they have received approval from the United States Food and Drug Administration (US FDA) to proceed with a new phase I clinical trial for Tekmira's lead oncology product, TKM-PLK1. This trial, run in parallel with the ongoing phase I trial of TKM-PLK1, provides Tekmira with an early opportunity to validate the drug's mechanism of action.

“Patients in this new study, who will have either primary liver cancer or liver metastases, will receive TKM-PLK1 delivered directly into the liver via Hepatic Artery Infusion (HAI). The trial design will allow us to measure tumour delivery, polo-like kinase 1 (PLK1) messenger RNA knockdown, and RNA interference (RNAi) activity in tumor biopsies from all of the patients treated,” said Dr Mark J Murray, Tekmira's president and CEO.

“This NCI clinical trial will run in parallel with our multi-centre TKM-PLK1 solid tumour phase I trial, currently underway at three centres in the United States. Working together on this clinical trial with our collaborators at the NCI will allow us to develop an even more robust data package to inform subsequent TKM-PLK1 development. We expect to have interim TKM-PLK1 clinical data before the end of 2011,” added Dr Murray.

The NCI trial is a phase I multiple-dose, dose escalation study testing TKM-PLK1 in patients with unresectable colorectal, pancreatic, gastric, breast, ovarian and esophageal cancers with liver metastases, or primary liver cancers. These patients represent a significant unmet medical need as they are not well served by currently approved treatments. The primary objectives of the trial include evaluation of the feasibility of administering TKM-PLK1 via HAI and to characterize the pharmacokinetics and pharmacodynamics of TKM-PLK1. Pharmacodynamic measurements will examine the effect of the drug on the patient's tumours, specifically aiming to confirm PLK1 knockdown and RNAi activity. Typically reserved for later stage trials, pharmacodynamic measurements are facilitated in this Phase 1 trial in part through the unique capabilities of the NCI Surgery Branch. Secondary objectives of the trial include establishing maximum tolerated dose and to evaluate response rate.

The NCI is one of the United States National Institutes of Health, the primary medical research agency in the US. The TKM-PLK1 trial will involve investigators at the NCI's Centre for Cancer Research (CCR) on the main NIH campus in Bethesda, Maryland.

TKM-PLK1 targets polo-like kinase 1, or PLK1, a cell cycle protein involved in tumour cell proliferation and a validated oncology target. Cancer patients whose tumours express high levels of PLK1 have a relatively poor prognosis. Inhibition of PLK1 prevents tumour cells from completing cell division, resulting in cell cycle arrest and cancer cell death.

RNAi therapeutics have the potential to treat a broad number of human diseases by "silencing" disease causing genes. The discoverers of RNAi, a gene silencing mechanism used by all cells, were awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi therapeutics, such as "siRNAs," require delivery technology to be effective systemically. LNP technology is one of the most widely used siRNA delivery approaches for systemic administration.

Tekmira's LNP technology (formerly referred to as stable nucleic acid-lipid particles or SNALP) encapsulates siRNAs with high efficiency in uniform lipid nanoparticles which are effective in delivering RNAi therapeutics to disease sites in numerous preclinical models. Tekmira's LNP formulations are manufactured by a proprietary method which is robust, scalable and highly reproducible and LNP-based products have been reviewed by multiple FDA divisions for use in clinical trials. LNP formulations comprise several lipid components that can be adjusted to suit the specific application.