Positive results from Alnylam's ALN-VSP Phase I trial for liver cancer

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it has completed its Phase I study with ALN-VSP, a systemically delivered RNAi therapeutic for the treatment of advanced solid tumors with liver involvement.

“Both primary liver cancer and metastatic disease of the liver are associated with poor prognosis for patients, and new therapies are clearly needed. Results from this study represent an important step in the development of a novel therapeutic strategy to treat this devastating disease.”

"We are very pleased with the results of our ALN-VSP Phase I trial that demonstrate safety and tolerability of multiple doses of ALN-VSP in addition to evidence for anti-tumor activity and proof of RNAi mechanism from tissue biopsy samples. Indeed, in this very advanced, heavily pre-treated cancer patient population, we have seen multiple patients achieve stable disease and one patient who has achieved a partial response with 70% tumor regression to date and who continues to receive drug after over one full year of treatment," said Jared Gollob, M.D., Senior Director of Clinical Research at Alnylam. "These data are not only important for the continued clinical advancement of our ALN-VSP program, but they also significantly increase our confidence in our broader pipeline of systemically delivered RNAi therapeutics."

In the Phase I study with ALN-VSP, 41 patients were enrolled and treated at doses ranging from 0.1 to 1.5 mg/kg. A total of 209 doses were administered, with a range of 1 to 28 doses per patient. Disease control (stable disease or better) was observed in 13 of 31 evaluable patients (42%) treated at doses of 0.4 to 1.5 mg/kg. The average duration of disease control is approximately five months, with a range of two to 14 months. Currently, five patients with disease control continue to receive ALN-VSP under an extension protocol; these include an endometrial cancer patient treated at 0.7 mg/kg with an ongoing partial response, as well as two renal cell cancer and two pancreatic neuroendocrine tumor patients treated at 1.0 mg/kg who have had stable disease for over four months.

"This Phase I study with ALN-VSP currently represents one of the most comprehensive clinical trials of a systemically delivered RNAi therapeutic, as well as one of the most extensive experiences with RNAi therapeutics in cancer," said Geoffrey Shapiro, M.D., Ph.D., Associate Professor, Department of Medicine at Harvard Medical School; Director, Early Drug Development Center, and Associate Professor, Medical Oncology at Dana-Farber Cancer Institute. "Both primary liver cancer and metastatic disease of the liver are associated with poor prognosis for patients, and new therapies are clearly needed. Results from this study represent an important step in the development of a novel therapeutic strategy to treat this devastating disease."

At the American Society of Clinical Oncology (ASCO) Annual Meeting in June 2011, Alnylam reported results from this trial which demonstrated that ALN-VSP was generally well tolerated, had single-agent anti-tumor activity, and showed RNAi-mediated target mRNA cleavage in both hepatic and extra-hepatic tumors. Disease control was achieved in one of 13 patients (8%) treated at doses less than or equal to 0.4 mg/kg versus 12 of 24 (50%) treated at doses greater than or equal to 0.7 mg/kg, including seven of 11 (64%) treated at the proposed Phase II dose of 1.0 mg/kg. A dose of 1.0 mg/kg administered every two weeks was identified as the regimen for further Phase II studies.