Alnylam Initiates Phase I Clinical Study of ALN-VSP in Patients with Liver Cancer
News Apr 06, 2009
Alnylam Pharmaceuticals has announced that it has initiated a Phase I human clinical trial of ALN-VSP to evaluate its safety, tolerability, pharmacokinetics, and pharmacodynamics in patients with advanced liver cancers, including hepatocellular carcinoma and other solid tumors with liver involvement.
ALN-VSP is an RNAi therapeutic comprised of two small interfering RNAs formulated in a lipid nanoparticle developed by Tekmira Pharmaceuticals Corporation and designed to target two genes critical in the growth and development of cancer cells: kinesin spindle protein, or KSP, required for tumor proliferation; and vascular endothelial growth factor, or VEGF, required for tumor growth.
Pre-clinical data in mouse tumor model studies have demonstrated robust efficacy of ALN-VSP, including suppression of targeted genes, demonstration of an RNAi mechanism of action, tumor reduction, and extension of survival.
“We are excited to have initiated this Phase I trial as it represents an important milestone in Alnylam’s efforts to advance RNAi therapeutics for the treatment of cancer. ALN-VSP is also Alnylam’s first clinical program employing systemic delivery. Moreover, in this program we are targeting two well-validated genes critical for tumor proliferation and survival, an attractive strategy for the advancement of novel anti-cancer medicines,” said Akshay Vaishnaw, M.D., Ph.D., Senior Vice President, Clinical Research at Alnylam.
“More than one million liver cancer patients are diagnosed annually, and currently have limited therapeutic options and extremely poor survival rates. Over time and as we aim to demonstrate safety and efficacy for ALN-VSP, we hope that our efforts will provide patients a meaningful treatment option for their disease.”
The Phase I trial, conducted in the U.S., is a multi-center, open label, dose escalation study designed to enroll approximately 55 patients with advanced solid tumors with liver involvement, who have failed to respond to or have progressed after standard treatment.
The primary objective is to evaluate the safety, tolerability, and pharmacokinetics of intravenous ALN-VSP, including demonstration of the maximum tolerated dose. Other exploratory objectives include the assessment of tumor response through Response Evaluation Criteria for Solid Tumors (RECIST), a set of published guidelines that define when cancer patients’ disease improves, stabilizes or progresses during treatment; change in tumor blood flow or vascular permeability measured by DCE-MRI; and, change in plasma biomarkers of angiogenesis.
In addition, the analysis of pharmacodynamic effects of ALN-VSP on tumors will be measured in patients electing to proceed with voluntary pre- and post-treatment biopsies.