Alnylam announces results from ALN-VSP Phase I study on liver cancers

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Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced results today from its Phase I extension study with ALN-VSP, a systemically delivered RNAi therapeutic for the treatment of advanced solid tumors with liver involvement. The data are being presented in a poster titled "Open-Label Extension Study of the RNAi Therapeutic ALN-VSP02 in Cancer Patients Responding to Therapy," in the Development Therapeutics - Experimental Therapeutics poster session being held Monday, June 4, 2012 from 8:00 a.m. to 12:00 p.m. CDT. Overall, the results demonstrated disease control lasting more than six months in the majority of patients treated on the extension study, including a complete response (CR) in an endometrial cancer patient who had multiple liver metastases. In this study, chronic dosing of up to 23 months with ALN-VSP was found to be generally safe and well tolerated.    

"We are very encouraged with the continued positive data from our ALN-VSP Phase I clinical trial and extension study. These data include safety and tolerability of multiple doses of ALN-VSP, as well as evidence for anti-tumor activity in this very advanced, heavily pre-treated cancer patient population. We have seen multiple patients achieve stable disease or better, including a patient with endometrial cancer metastatic to the liver who has achieved a complete response," said Jared Gollob, M.D., Senior Director of Clinical Research at Alnylam. "Results from the extension study also give us increased confidence in long-term chronic dosing with RNAi therapeutics delivered via LNPs, as patients have received drug twice a month for up to nearly two years, and approximately 11 months on average. We look forward to partnering this program to further advance the clinical development of ALN-VSP as we believe the evidence of anti-tumor activity warrants Phase II testing."

The extension study included patients enrolled in the ALN-VSP Phase I trial who achieved stable disease (SD) or better after four months of treatment; patients were eligible to continue on the extension study until disease progression. Main objectives included continued evaluation of safety and tolerability and assessment of disease response. Seven of 37 patients (18.9%) evaluable for response went onto the extension study. These included 1 of 7 (14.2%) at 0.4 mg/kg, 2 of 5 (40%) at 0.7 mg/kg, and 4 of 11 (36.3%) at 1.0 mg/kg. At the time of enrollment, six patients had SD and one had an unconfirmed partial response. For these patients treated on both the Phase I trial and extension study, the average length of time on treatment was 10.5 months, with a range of five to 23 months. As of today, two patients remain on the extension study, including an endometrial cancer patient on study for 23 months who achieved a CR after 20 months of treatment at 0.7 mg/kg and one patient with pancreatic neuroendocrine tumor (PNET) with continued SD after 14.5 months of treatment at 1.0 mg/kg. A PNET patient and a renal cell carcinoma patient who achieved SD at 1.0 mg/kg came off the study after 5.5 and 8.5 months, respectively, for adverse events that included grade 3 elevated alkaline phosphatase or grade 2 fatigue deemed possibly related to study drug.

"Both primary liver cancer and metastatic disease of the liver are associated with poor prognosis for patients, and new therapies are clearly needed," said Josep Tabernero, M.D., Chairman of the Medical Oncology Department and Phase I Program at Vall d'Hebron University Hospital in Barcelona, Spain. "This Phase I trial and extension study with ALN-VSP currently represents, to our knowledge, one of the most comprehensive clinical trials of a systemically delivered RNAi therapeutic and also one of the most extensive experiences with RNAi therapeutics in cancer. The safety data and anti-tumor activity with ALN-VSP, including a complete response in a patient with multiple liver metastases who had failed multiple prior therapies, are very encouraging and I look forward to the further development of this promising agent."

Results from the extension study showed that chronic bi-weekly dosing with ALN-VSP up to 1.0 mg/kg was generally safe and well tolerated in this setting. No new toxicities were reported among the seven patients enrolled onto the extension study. A decrease in spleen volume, likely an on-target anti-kinesin spindle protein (KSP) effect based on pre-clinical findings and not associated with any adverse events, occurred to a greater degree on the extension study than in the Phase I trial and was most pronounced in patients receiving 12 or more doses.    


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