Health & Fitness
Health and Fitness
Health and Fitness
Wed, June 29, 2011
Tue, June 28, 2011 Alnylam Presents New Data from ALN-TTR Program at Peripheral Nerve Society Meeting
CAMBRIDGE, Mass.--([ BUSINESS WIRE ])--[ Alnylam Pharmaceuticals ], Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it is presenting new data from its ALN-TTR program at the 2011 Peripheral Nerve Society Meeting being held in Potomac, Maryland. The company is reporting results from a natural history study which was designed to measure blood levels of wild-type and mutant transthyretin (TTR) over time in both transthyretin-mediated amyloidosis (ATTR) patients and gene carriers. The study was performed at Boston Medical Center under the direction of John Berk, M.D., who leads the Amyloid Clinical Program at Boston University School of Medicine. ALN-TTR01 is currently in a Phase I clinical trial for the treatment of ATTR.
"a major scientific breakthrough that happens once every decade or so"
aWe are pleased with the progress we are making in our ALN-TTR program and remain on track to report data from our Phase I trial in the third quarter of this year. The new data presented at the Peripheral Nerve Society Meeting define blood levels of circulating transthyretin in ATTR patients and gene carriers, and are informative in our efforts to develop our RNAi therapeutic for this devastating disease,a said Akshay K. Vaishnaw, M.D., Ph.D., Senior Vice President and Chief Medical Officer of Alnylam. aIn addition to progress in our ALN-TTR program, we remain on track in our other aAlnylam 5x15a"a™ programs. Specifically, we expect to file our regulatory documents in the coming weeks to begin a Phase I trial with ALN-PCS for the treatment of severe hypercholesterolemia, and we remain on track to report human proof-of-concept data from the ALN-PCS program by year end.a
ATTR is caused by mutations in the TTR gene, which is expressed predominantly in the liver, and is characterized by the abnormal accumulation of mutant and wild-type TTR protein deposits in multiple extra-hepatic tissues, including the peripheral nervous system, heart, and gastrointestinal tract. Although it is known that serum TTR concentrations in ATTR patients and gene carriers are below the normal range, little is known about temporal changes in TTR levels in either patients or carriers. Accordingly, Alnylam conducted a natural history study to measure serial TTR levels over a four week period in ATTR patients and gene carriers, and to determine the intra- and inter-patient variability in serum TTR. The study enrolled 26 patients and gene carriers with seven different amyloidogenic TTR mutations, the most common being the Val30Met mutation that is the primary cause of familial amyloidotic polyneuropathy (FAP). The data from this study showed that TTR levels were stable over time in patients and carriers. The average serum TTR concentration was approximately 200 micrograms/mL with 10 to 20% intra-subject variability over the 28-day observation period. Results showed that inter-subject TTR variability was approximately 25%.
Alnylam scientists and collaborators also presented pre-clinical data from its ALN-TTR program, including new data demonstrating improved potency with ALN-TTR01 using a loading dose/maintenance dose regimen.
About ALN-TTR Phase I Study
ALN-TTR01 is currently in a blinded, randomized, placebo-controlled, single dose escalation Phase I clinical trial in patients with ATTR. The primary objective of this trial is to evaluate the safety and tolerability of a single dose of ALN-TTR01, with patients being enrolled into sequential cohorts of increasing doses. Secondary objectives include characterization of plasma and urine pharmacokinetics of ALN-TTR01 and assessment of pharmacodynamic activity based on serial measurements of circulating TTR serum levels. The European Commission has designated ALN-TTR01 as an orphan medicinal product for the treatment of familial amyloidotic polyneuropathy (FAP). In parallel, Alnylam is also advancing ALN-TTR02, which utilizes proprietary second-generation delivery technology, and is on track to file an investigational new drug (IND) or IND equivalent application in the second half of 2011.
About TTR-Mediated Amyloidosis
TTR-mediated amyloidosis (ATTR) is a hereditary, systemic disease caused by a mutation in the transthyretin (TTR) gene. TTR protein is produced primarily in the liver and is normally a carrier for thyroid hormones and retinol binding proteins. The mutation causes abnormal amyloid proteins to accumulate in and damage body organs and tissue such as the peripheral nerves and heart, resulting in intractable peripheral sensory neuropathy, autonomic neuropathy, and cardiomyopathy. In its severest form, ATTR represents a tremendous unmet medical need with significant morbidity and mortality as an orphan disease; combined, FAP (familial amyloidotic polyneuropathy) and FAC (familial amyloidotic cardiomyopathy) affect approximately 50,000 people worldwide. ATTR patients with FAP have a mean life expectancy of five to 15 years from symptom onset and the only treatment option is liver transplantation; as a result there is a significant need for novel therapeutics to treat patients who have a mutation in the TTR gene.
About aAlnylam 5x15a"a
The aAlnylam 5x15a strategy, launched in January 2011, establishes a path for development and commercialization of novel RNAi therapeutics to address genetically defined diseases with high unmet medical need. Products arising from this initiative share several key characteristics including: a genetically defined target and disease; the potential to have a major impact in a high unmet need population; the ability to leverage the existing Alnylam RNAi delivery platform; the opportunity to monitor an early biomarker in Phase I clinical trials for human proof of concept; and the existence of clinically relevant endpoints for the filing of a new drug application (NDA) with a focused patient database and possible accelerated paths for commercialization. This strategy leverages Alnylama™s clinical progress on siRNA delivery, including definitive human proof-of-concept data for systemic delivery. By the end of 2015, the company expects to have five such RNAi therapeutic programs in advanced clinical development. These include ALN-TTR for the treatment of transthyretin-mediated amyloidosis (ATTR), ALN-PCS for the treatment of severe hypercholesterolemia, ALN-HPN for the treatment of refractory anemia, and two additional programs from the companya™s ongoing discovery efforts that will be designated and advanced into development later in 2011. Alnylam intends to commercialize the products arising under the aAlnylam 5x15a strategy itself in the United States and potentially certain other countries; the company will seek development and commercial partners in other global territories.
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 aa major scientific breakthrough that happens once every decade or so,a 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 Alnylama™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 Alnylam Pharmaceuticals
Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is leading the translation of RNAi as a new class of innovative medicines with a core focus on RNAi therapeutics for the treatment of genetically defined diseases, including ALN-TTR for the treatment of transthyretin-mediated amyloidosis (ATTR), ALN-PCS for the treatment of severe hypercholesterolemia, and ALN-HPN for the treatment of refractory anemia. As part of its aAlnylam 5x15TMa strategy, the company expects to have five RNAi therapeutic products for genetically defined diseases in advanced stages of clinical development by the end of 2015. Alnylam has additional partner-based programs in clinical or development stages, including ALN-RSV01 for the treatment of respiratory syncytial virus (RSV) infection, ALN-VSP for the treatment of liver cancers, and ALN-HTT for the treatment of Huntingtona™s disease. The companya™s leadership position on RNAi therapeutics and intellectual property have enabled it to form major alliances with leading companies including Merck, Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko Kirin, and Cubist. In addition, Alnylam and Isis co-founded Regulus Therapeutics Inc., a company focused on discovery, development, and commercialization of microRNA therapeutics; Regulus has formed partnerships with GlaxoSmithKline and sanofi-aventis. Alnylam has also formed Alnylam Biotherapeutics, a division of the company focused on the development of RNAi technologies for application in biologics manufacturing, including recombinant proteins and monoclonal antibodies. Alnylam scientists and collaborators have published their research on RNAi therapeutics in over 100 peer-reviewed papers, including many in the worlda™s top scientific journals such as Nature, Nature Medicine, Nature Biotechnology, and Cell. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, please visit [ www.alnylam.com ].
Alnylam Forward-Looking Statements
Various statements in this release concerning Alnylama™s future expectations, plans and prospects, including without limitation, statements regarding Alnylama™s expectations with respect to its aAlnylam 5x15a product strategy, Alnylama™s views with respect to the potential for RNAi therapeutics, including ALN-TTR01 and ALN-TTR02, ALN-PCS, and ALN-HPN, its expectations with respect to the timing and success of its clinical and pre-clinical trials, including its plan to file INDs or IND equivalent applications and initiate clinical trials for ALN-TTR02, ALN-PCS, and ALN-HPN, the expected timing of regulatory filings, and its expectations regarding human proof of concept data, 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, without limitation, Alnylama™s ability to discover and develop novel drug candidates, the pre-clinical and clinical results for its product candidates, which may not support further development of such product candidates, Alnylama™s ability to successfully demonstrate the efficacy and safety of its drug candidates in human clinical trials and establish and maintain strategic business alliances and new business initiatives, as well as those risks more fully discussed in the aRisk Factorsa 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 Alnylama™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.
