Alnylam presents interim data from ALN-VSP02 Phase I trial for liver cancer at ASCO 2010

March 02, 2016

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 as measured by Dynamic Contrast - Enhanced Magnetic Resonance Imaging (DCE-MRI); change in plasma biomarkers of angiogenesis; and, molecular and cellular analyses of tumor biopsy samples.

ALN-VSP was well-tolerated in most patients to date. A total of 62 doses have been administered to 19 patients receiving 0.1, 0.2, 0.4, or 0.7 mg/kg ALN-VSP. The majority of these patients had colorectal cancer, a primary tumor that often metastasizes to the liver. There were two mild acute infusion reactions at 0.4 and 0.7 mg/kg; both patients had no further reactions with slowing of the infusion and stayed on the trial. At 0.7 mg/kg, a patient with advanced pancreatic neuroendocrine cancer with extensive involvement of the liver developed hepatic failure five days following the second dose and subsequently died; this was deemed possibly related to study drug. Six additional patients treated at 0.7 mg/kg did not exhibit any evidence of hepatotoxicity. Maximum tolerated dose has not yet been reached and active enrollment is continuing.

Pharmacokinetic data showed that Cmax (peak serum concentration of drug) and area under the curve (AUC) were dose proportional with no evidence of drug accumulation. In addition, DCE-MRI results were suggestive of an anti-VEGF effect in the majority of treated patients. In 62% of evaluable liver tumors, there was a greater than 40% decline in Ktrans (measure of blood flow), an effect that is comparable to what has been observed with other anti-VEGF drugs in solid tumors (Cannistra et al., Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S, 2006; and Siegel et al., Journal of Clinical Oncology, Vol 26, No 18: pp. 2992-2998, 2008). Molecular and cellular analyses of biopsy samples are ongoing.

"We are encouraged by the results we have seen to date with ALN-VSP in this trial, which include tolerability data, as well as preliminary data on potential pharmacodynamic effects in this very advanced cancer patient population. The maximum tolerated dose has not yet been reached, and we continue to enroll patients in a dose-escalating manner," said Akshay Vaishnaw, M.D., Ph.D., Senior Vice President, Clinical Research at Alnylam. "We look forward to the further development of this promising agent and completion of this trial. Indeed, this is an important study that, to our knowledge, currently represents one of the most comprehensive clinical trials of systemically delivered RNAi therapeutics and also one of the most extensive experiences of RNAi therapeutics in cancer."

ALN-VSP is Alnylam's first systemic RNAi program and represents the company's first clinical program in oncology. The drug is formulated in a lipid nanoparticle developed by Tekmira Pharmaceuticals Corporation.

SOURCE Alnylam Pharmaceuticals