Alnylam and Medtronic Present New Late-Stage Pre-clinical Data on ALN-HTT, an RNAi Therapeutic for the Treatment of Huntington`s Disease
New Data Demonstrate Broad CNS Distribution and Robust Therapeutic Silencing of Gene Responsible for Huntington`s Disease
Continuous 28-Day CNS Infusion of ALN-HTT Found to be Safe and Well Tolerated
VANCOUVER, B.C.--(Business Wire)--
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."
This research was done with the laboratory of Don M. Gash, Ph.D. at the
University of Kentucky College of Medicine, whose team is internationally
recognized for developing new therapeutic approaches to treating
neurodegenerative diseases, and have unparalleled expertise in direct drug
delivery to the brain.
In February 2005, Alnylam formed a collaboration with Medtronic to pursue the
development of novel drug-device combinations incorporating RNAi therapeutics to
treat neurodegenerative disorders. In July 2007, the companies advanced their
collaboration on their Huntington`s disease program into development stages,
following positive pre-clinical data generated under the initial joint
technology development phase of the program. In addition, the agreement was
revised as a 50-50 partnership in the United States.
About Huntington`s Disease
Huntington`s disease is an autosomal dominant neurodegenerative genetic disease
that afflicts approximately 30,000 patients in the U.S., with an estimated
200,000 additional patients having a 50% risk of developing the disease. The
average lifespan for patients after onset is approximately 10 to 20 years. There
are currently no effective therapies available for the treatment of Huntington`s
disease.
About RNA Interference (RNAi)
RNAi (RNA interference) is a revolution in biology, representing a breakthrough
in understanding how genes are turned on and off in cells, and a completely new
approach to drug discovery and development. Its discovery has been heralded as
"a major scientific breakthrough that happens once every decade or so," and
represents one of the most promising and rapidly advancing frontiers in biology
and drug discovery today which was awarded the 2006 Nobel Prize for Physiology
or Medicine. 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. Small interfering RNAs
(siRNAs), the molecules that mediate RNAi and comprise Alnylam`s RNAi
therapeutic platform, target the cause of diseases by potently silencing
specific mRNAs, thereby preventing disease-causing proteins from being made.
RNAi therapeutics have the potential to treat disease and help patients in a
fundamentally new way.
About Medtronic
Medtronic, Inc. (www.medtronic.com), headquartered in Minneapolis, is the global
leader in medical technology - alleviating pain, restoring health and extending
life for millions of people around the world.
About Alnylam Pharmaceuticals
Alnylam is a biopharmaceutical company developing novel therapeutics based on
RNA interference, or RNAi. The company is applying its therapeutic expertise in
RNAi to address significant medical needs, many of which cannot effectively be
addressed with small molecules or antibodies, the current major classes of
drugs. Alnylam is leading the translation of RNAi as a new class of innovative
medicines with peer-reviewed research efforts published in the world`s top
scientific journals including Nature, Nature Medicine, and Cell. The company is
leveraging these capabilities to build a broad pipeline of RNAi therapeutics;
its most advanced program is in Phase II human clinical trials for the treatment
of respiratory syncytial virus (RSV) infection and is partnered with Cubist and
Kyowa Hakko. In addition, the company is developing RNAi therapeutics for the
treatment of a wide range of disease areas, including liver cancers,
hypercholesterolemia, Huntington`s disease, and TTR amyloidosis. The company`s
leadership position in fundamental patents, technology, and know-how relating to
RNAi has enabled it to form major alliances with leading companies including
Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko, and Cubist. To
reflect its outlook for key scientific, clinical, and business initiatives,
Alnylam established "RNAi 2010" in January 2008 which includes the company`s
plan to significantly expand the scope of delivery solutions for RNAi
therapeutics, have four or more programs in clinical development, and to form
four or more new major business collaborations, all by the end of 2010. Alnylam
is a joint owner of Regulus Therapeutics, a joint venture focused on the
discovery, development, and commercialization of microRNA therapeutics. Founded
in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more
information, please visit http://www.alnylam.com.
Medtronic Forward Looking Statement
Any forward-looking statements are subject to risks and uncertainties such as
those described in Medtronic`s Annual Report on Form 10-K for the year ended
April 24, 2009. Actual results may differ materially from anticipated results.
Alnylam Forward-Looking Statement
Various statements in this release concerning Alnylam`s future expectations,
plans and prospects, constitute forward-looking statements for the purposes of
the safe harbor provisions under The Private Securities Litigation Reform Act of
1995. Actual results may differ materially from those indicated by these
forward-looking statements as a result of various important factors, including
the company`s ability to successfully research and develop ALN-HTT, including
the ability to achieve acceptable safety and efficacy results in humans, as well
as those risks more fully discussed in the "Risk Factors" section of its most
recent quarterly report on Form 10-Q on file with the Securities and Exchange
Commission. In addition, any forward-looking statements represent Alnylam`s
views only as of today and should not be relied upon as representing its views
as of any subsequent date. Alnylam does not assume any obligation to update any
forward-looking statements.