Zeroing in on Huntington’s

Alnylam, Medtronic and CHDI Foundation form collaboration to advance RNAi therapeutic for Huntington’s disease

CAMBRIDGE, Mass.—In an effort to put Huntington's disease squarely in the crosshairs, Alnylam Pharmaceuticals Inc., Medtronic Inc. and CHDI Foundation Inc. have forged a collaboration to advance ALN-HTT, a novel drug-device combination for the treatment of the disease.

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference (RNAi). Medtronic is a global leader in medical technology, while CHDI is a privately funded, not-for-profit, virtual biotech company that is exclusively dedicated to rapidly discovering and developing therapies that slow the progression of Huntington's disease.

Under this new collaboration, CHDI has agreed to initially fund up to approximately 50 percent of the IND-enabling activities, representing more than $10 million in funding. The agreement between Alnylam and Medtronic will remain as a 50-50 partnership in the United States. Medtronic will commercialize the therapy consisting of the RNAi compound and delivery device.  

In the collaboration, Alnylam will focus on the RNAi therapeutic component of ALN-HTT, and Medtronic will focus on the implantable device used to deliver the RNAi therapeutic.

ALN-HTT consists of an RNAi therapeutic targeting huntingtin—the gene responsible for Huntington's disease—that is being developed for delivery to the central nervous system (CNS) using an implantable infusion system developed by Medtronic.

Huntington's disease is an autosomal dominant neurodegenerative genetic disorder that causes motor, cognitive and behavioral dysfunction. It is estimated that 120,000 people in the United States have the genetic mutation that causes Huntington's disease and will experience symptoms during a normal lifetime. The average lifespan for patients after onset of motor dysfunction is approximately 10 to 20 years. There are currently no disease-modifying therapies available to slow the progression of Huntington's disease.

Dinah Sah, vice president of research at Alnylam, says adding CHDI as a partner to the company's Huntington's disease program is a boon for the effort.

"They bring a tremendous amount of disease area expertise that will contribute to advancing ALN-HTT towards the clinic with Medtronic," Sah says. "Our preclinical data provide a strong rationale for this program, and we remain encouraged by the potential that ALN-HTT may offer to patients."

Moreover, Sah notes that CHDI brings a tremendous amount of expertise in Huntington's disease that will prove invaluable to the advancement of ALN-HTT as it gets even closer to the clinic.  

"In addition, CHDI also brings an important connection to physicians and patients, where we have a commitment to advance such an important disease-modifying therapy," she says.

According to Sah, Alnylam initiated its original collaboration with Medtronic in February 2005, when the companies began to pursue potential RNAi therapeutic-device combinations designed to treat neurodegenerative disorders such as Huntington's, Alzheimer's and Parkinson's diseases.   

"We decided to focus on Huntington's disease because of the definitive genetic evidence that mutant huntingtin is causal for the disease in all Huntington's patients," she says.
According to Robi Blumenstein, president of CHDI Management, Alnylam and Medtronic have shown leadership and encouraging progress in developing a novel drug-device combination for the treatment of Huntington's disease.

"Their collaborative approach demonstrates a combined commitment to tackle this devastating disease and this program is closely aligned with CHDI's mission," Blumenstein says. "We welcome the opportunity to accelerate this program and look forward to continued advancement toward clinical testing in patients."

And the backing of CHDI is just what the longtime collaborators wanted to hear.

"We kind of felt that we were on the right track, and we view this as a true third-party endorsement that we really are the leading contender right now to have a major impact on patients with Huntington's," says Lothar Krinke, vice present of research and business development for Medtronic. "They gave us a true, independent assessment of our program. They are a not-for-profit, entirely patient-oriented organization, and they've chosen to invest in us, so we see this as a validation of our work."

Krinke explains that Huntington's was also selected for the initial collaboration with Alnylam because the partners recognized an unmet medical need for patients suffering with the disease.

"Secondly, we chose this as a focus because Huntingston's is a genetic disorder," he explains. "We know what causes it and siRNA or RNAi would work anywhere. For neurodegenerative diseases, Huntington's was the one where it would be most likely to work because we know it is genetic and we could shut down the genes with RNAi."
It was less clear with Parkinson's and Alzheimer's' diseases. While they can be genetic, Krinke says there are other causes of the diseases that could potentially limit initial success of the research effort.

Sah points out that results generated from this study will provide an RNAi-device platform that is applicable to other diseases of the human nervous system, such as Parkinson's disease.

"We are interested in other areas, but we haven't ventured there yet in the clinic," Krinke adds. "We do see potential to expand this research there in the future."

Gregory Stewart, director of CNS Drug Therapy Research and Development in Medtronic's Neuromodulation business, says the ALN-HTT program represents an exciting opportunity to combine innovative medicines with drug delivery technology in an area of extreme unmet medical need.

"With no effective disease-modifying therapies available currently for patients afflicted with Huntington's disease, the collaboration between Alnylam and Medtronic, and now support from CHDI, will work to develop a novel treatment strategy for this devastating neurodegenerative disease," he notes.

Sah says the partnership has a clear yardstick with which to measure success of its efforts.

"With this collaboration, Alnylam, Medtronic, and CHDI hope to facilitate the advancement of this program towards the clinic and ultimately be able to provide a novel therapeutic option for patients suffering from this devastating disease," Sah concludes.

"Ultimately, the true measure of our success is to help patients and that is a couple of years away," Krinke adds. "In the short term, we need to complete our preclinical studies and enter Phase I. We will measure success on how fast we move through the clinic and to the next phases."



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