Medical Device Daily
Medtronic (Minneapolis) and Alnylam Pharmaceuticals (Cambridge, Massachusetts), an RNAi therapeutics company, reported that they are advancing their collaboration initiated in February 2005 (Medical Device Daily , Feb. 10, 2005), following positive pre-clinical data generated under the initial joint technology development phase of the program.
The companies will focus on developing a drug device combination for the treatment of Huntington’s disease, an inherited neurological disorder characterized by abnormal body movements and a progressively worsening level of coordination. The product is expected to consist of an RNAi therapeutic targeting the Huntington’s disease gene that will be delivered by Medtronic’s implantable infusion pump. The companies said they might also decide to collaborate on the development of similar drug device combinations using Alnylam’s RNAi therapeutics platform and Medtronic’s implantable infusion pump for the treatment of other neurodegenerative diseases, such as Parkinson’s disease.
The agreement has also been revised as a 50/50 relationship in the U.S. Medtronic will commercialize the therapy consisting of the identified RNAi compound and advanced delivery devices. In the U.S., Alnylam has the opportunity to invest in clinical development of this therapy through product launch. In Europe, Medtronic is solely responsible for development and commercialization, the companies said.
Alnylam told Medical Device Daily in an email that the company believes there are several reasons why RNAi has potential for neurological diseases, including Huntington’s disease.
“Many of the key targets are ‘undruggable.’ Some companies are trying small molecule approaches to prevent aggregation of synuclein, huntingtin, amyloid, etc., but the results have not been very encouraging,” Alnylam said. “These approaches assume that aggregation is the cause of the pathology, and they may actually be the result. Antibodies may have promise in clearing amyloid for example, but only siRNAs have the potential of actually preventing the production of these disease-causing agents in the first place.”
Another reason, the company added, is the multiple proof-of-concept experiments in animal models of neurological disease.
“These experiments demonstrate that partial reduction of the disease-causing gene results in robust efficacy with regard to survival, behavior and pathology; full silencing is not needed,” Alnylam said.
“We have been very pleased with the progress made to date by the scientific teams at Alnylam and Medtronic. Pre-clinical data from our Huntington’s disease program provide a strong rationale to advance an RNAi therapeutic program forward for this important disease where there are simply no effective therapies for patients today,” said John Maraganore, president/CEO of Alnylam, in a joint statement with Medtronic.
Medtronic is being tight-lipped about the development of the drug device combination. Marybeth Thorsgaard, a spokesperson for Medtronic, told MDD that the company declined to comment about the technology beyond what it stated in the press release “for competitive reasons.”
“We have proven expertise in delivering targeted therapies throughout the body, while Alnylam brings leadership in the evolving science of RNAi technology,” said Stephen Oesterle, MD, Medtronic’s senior VP of medicine and technology, in the joint release. “Together, we are well positioned to explore drug-device combinations with a goal of discovering better ways to treat serious neurodegenerative diseases.”
Alnylam said it has reported on data in its Huntington’s disease program in a number of scientific meetings. Most recently, at the Keystone Symposium “RNAi for Target Validation and as a Therapeutic” in January, Alnylam collaborators presented in vivo data demonstrating that an siRNA targeting the Huntington gene inhibited the progression of Huntington’s disease in a mouse model.
These results showed both a reduction of neuronal pathology and an improvement in abnormal behavior, where pathological protein aggregates were decreased by about 70% and two types of abnormal behavior — clasping and footslips — were ameliorated by about 50% and 70%, respectively. In addition, levels of the Huntington protein that mediates Huntington’s disease were reduced by about 70%.
RNAi is a revolution in biology, according to Alnylam, representing a breakthrough in understanding how genes are turned on and off in cells, and a new approach to drug discovery and development. It represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today and was awarded the 2006 Nobel Prize for Physiology or Medicine, the company said.
RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. RNAi therapeutics target the cause of diseases by potently silencing specific messenger RNAs (mRNAs), thereby preventing disease-causing proteins from being made.