Alnylam and Medtronic announce pre-clinical research findings from their Huntington’s disease program

Sep 15 2009

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, and Medtronic, Inc. (NYSE: MDT), the world’s leading developer of medical devices, announced today the presentation of new pre-clinical research findings from their Huntington’s disease program at the 2009 World Congress on Huntington’s Disease held September 12-15, 2009 in Vancouver, British Columbia. Together, the two companies are developing a drug-device combination for the treatment of Huntington’s disease. The drug, ALN-HTT, consists of an RNAi therapeutic targeting huntingtin, the gene responsible for Huntington’s disease, and is delivered to the central nervous system (CNS) using an implantable pump infusion system developed by Medtronic.

The newly presented pre-clinical research, performed in collaboration with Professor Don M. Gash’s laboratory at the University of Kentucky College of Medicine, demonstrate that a small interfering RNA (siRNA) targeting the huntingtin gene achieves broad distribution in the CNS following continuous direct CNS administration. Further, direct delivery to the CNS resulted in robust silencing of the huntingtin gene mRNA, extending previously presented pre-clinical data. This silencing effect was achieved at substantial distances from the infusion site, an important step towards translating this delivery approach from animal models to the larger human brain. Additional pre-clinical studies showed ALN-HTT to be well tolerated following continuous direct CNS administration over a period of approximately one month.

“We are very pleased with these promising results in our Huntington’s disease program, as it continues to represent an exciting opportunity to combine innovative medicines with our state-of-the-art drug device delivery technology in an area of extreme unmet medical need,” said Gregory Stewart Ph.D., Director of CNS Drug Therapy R&D at Medtronic. “With no currently effective disease-modifying therapies for patients afflicted with Huntington’s, the convergence of Alnylam and Medtronic technologies could provide a novel treatment strategy for this devastating neurodegenerative disease.”

The new pre-clinical studies presented at this meeting employed direct delivery of ALN-HTT to the striatum using implantable infusion pumps and convection-enhanced delivery (CED), or continuous infusion under positive pressure. Specifically, the new data showed that direct CNS administration of ALN-HTT resulted in:

• broad distribution of the siRNA across the CNS, including the striatum and surrounding brain regions;
• silencing of the huntingtin gene mRNA by an average of approximately 45% in the putamen following continuous infusion over seven days, as well as reductions in the levels of huntingtin protein as demonstrated by immunohistochemistry;
• silencing of the huntingtin gene messenger RNA (mRNA) in the CNS at significant distances from the infusion site; and,
• a safe and well tolerated profile following continuous infusion over 28 consecutive days, with no clinical abnormalities, neurological behavioral signs, and no clinically significant findings in histopathological examination of the brain.

“We are very excited by our new findings as they represent a major leap forward in our Huntington’s disease program across multiple dimensions,” said Dinah Sah, Ph.D., Vice President, Research, CNS, and Oncology of Alnylam. “Indeed, in our new ALN-HTT research findings, we have extended our earlier data in more advanced pre-clinical studies including key findings on siRNA biodistribution in the CNS, therapeutic silencing of the disease-causing huntingtin gene in a manner supportive of scaled effects for the human brain, and safety assessment following continuous infusion in the CNS over approximately one month. In aggregate, these new studies – which were performed in collaboration with the University of Kentucky, one of the leading academic institutions for research on direct CNS delivery for neurodegenerative diseases – support our continued and combined efforts with Medtronic to advance this important innovation to patients.”