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http://phx.corporate-ir.net/phoenix.zhtml?c=148005&p=irol-newsA 9293&highlight= 没那么夸张,只是phase I study 有效果而已。。。 Alnylam and Collaborators Publish Results from Phase I Clinical Trial and Ex tension Study with ALN-VSP, an RNAi Therapeutic for the Treatment of Liver C ancer - Results Published in Cancer Discovery Document Most Comprehensive Human Ex perience To Date for RNAi Therapeutics Delivered with Lipid Nanoparticles (L NPs) - CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jan. 30, 2013-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, and collaborators announced today the publication of complete study results from a Phase I tri al with ALN-VSP, a systemically delivered RNAi therapeutic for the treatment of advanced solid tumors with liver involvement. The paper, titled 揊irst-i n-Man Trial of an RNA Interference Therapeutic Targeting VEGF and KSP in Can cer Patients with Liver Involvementappears as an OnlineFirst publication i n the journal Cancer Discovery (Tabernero et al., Cancer Discovery CD-12-042 9; Published OnlineFirst January 2013). The study results document anti-tumo r activity for ALN-VSP in a heavily pre-treated and advanced patient populat ion, including a complete response in an endometrial cancer patient who had multiple hepatic metastases. In addition, this study provided proof of RNAi mechanism in man based on molecular analysis of biopsy samples from patients . Finally, in this study the most comprehensive study of a systemically ad ministered RNAi therapeutic to date chronic dosing of ALN-VSP for up to 26 months was found to be generally safe and well tolerated. 揙ur ALN-VSP Phase I clinical trial defines the most comprehensive human exp erience for RNAi therapeutics delivered with lipid nanoparticle formulations . Results from this study highlight safety and tolerability of multiple dose s of ALN-VSP, proof of RNAi activity in man, and evidence for anti-tumor act ivity in a very advanced, heavily pre-treated cancer patient population,sa id Jared Gollob, M.D., Vice President, Clinical Research at Alnylam. 揥e are encouraged by the anti-tumor activity observed in this study in multiple pa tients who achieved stable disease or better; this includes a patient with e ndometrial cancer metastatic to the liver who achieved a complete response. Results from the extension study also give us increased confidence in long-t erm chronic dosing for RNAi therapeutics delivered with lipid nanoparticle f ormulations, as patients received an average of over 11 months of treatment overall, including one patient who received treatment for over two full year s.br /> ALN-VSP is a systemically delivered RNAi therapeutic using first-generation lipid nanoparticle (LNP) or 揝NALPdelivery technology that comprises two s iRNAs targeting two genes critical for the growth and development of cancer cells: vascular endothelial growth factor (VEGF) and kinesin spindle protein (KSP). The ALN-VSP Phase I trial was designed as a multi-center, open-label , dose-escalation study in patients with advanced solid tumors with liver in volvement who failed to respond to or had progressed after standard treatmen t. A total of 41 patients were enrolled. The primary objective was to evalua te the safety, tolerability, and pharmacokinetics of intravenously administe red ALN-VSP given every two weeks. Other secondary and exploratory objective s included: assessment of tumor response using Response Evaluation Criteria for Solid Tumors (RECIST); quantitation of change in tumor blood flow and va scular permeability as measured by dynamic contrast-enhanced magnetic resona nce imaging (DCE-MRI); and, analysis of pharmacodynamic effects of ALN-VSP o n tumors as measured in patients electing to proceed with voluntary pre- and post-treatment biopsies. Results of the Phase I study in 41 patients were previously presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in 2011 and dem onstrated proof of RNAi mechanism based on liver biopsy samples and disease control (stable disease or better after first two months) in 13/31 (42%) pat ients treated at doses greater than or equal to 0.4 mg/kg. ALN-VSP was gener ally safe and well tolerated up to a dose of 1.0 mg/kg. The most common adve rse events were grade 1-2 fatigue (24% of patients), nausea (17% of patients ) and fever (17% of patients), with no clear dose relationship. There were a lso no dose-dependent changes in liver function tests. Grade 2 infusion-rela ted reactions were observed in 15% of patients, or 3% of total doses adminis tered; these reactions responded to slowing of the infusion of drug, and no patients discontinued therapy because of an infusion reaction. Dose-limiting toxicities included: liver failure and death in one patient with extensive hepatic metastases involving greater than 70% of liver mass and prior splene ctomy/partial hepatectomy at 0.7 mg/kg; transient grade 3 thrombocytopenia i n two patients at 1.25 mg/kg; and grade 3 hypokalemia in one patient at 1.5 mg/kg. The ALN-VSP extension study was designed to enable continued dosing with ALN -VSP in patients who had achieved stable disease or better after completing four months of treatment on the Phase I trial. Patients enrolled onto the ex tension study were permitted to receive bi-weekly ALN-VSP at the same dose l evel that they had been safely treated with in the Phase I study until disea se progression or unacceptable toxicity; a total of seven patients were enro lled. The primary objective was to collect long-term safety data. The second ary objective was to assess tumor response. Results from the extension study were previously presented at the American S ociety of Clinical Oncology (ASCO) Annual Meeting in 2012 and demonstrated t hat chronic dosing with ALN-VSP up to 1.0 mg/kg was generally safe and well tolerated in this setting. On average, patients received bi-weekly treatment s for 11.3 months. An endometrial cancer patient achieved a complete respons e (CR) after 20 months of treatment at 0.7 mg/kg and remained in remission u pon completion of 26 months of therapy. A patient with pancreatic neuroendoc rine tumor (PNET) treated at 1.0 mg/kg remained on study with stable disease (SD) for 18 months, and two patients with renal cell carcinoma (RCC) treate d at 1.0 mg/kg remained on study with SD for approximately 8-12 months. No n ew toxicities were reported among the patients enrolled onto the extension s tudy. A PNET patient and an RCC patient who achieved SD at 1.0 mg/kg came of f the study after 5.5 and 8.5 months, respectively, for adverse events that included grade 3 elevated alkaline phosphatase or grade 2 fatigue deemed pos sibly related to study drug. A decrease in spleen volume, likely an on-targe t anti-KSP effect and not associated with any adverse events, occurred to a greater degree on the extension study than in the Phase I trial and was most pronounced in patients receiving 12 or more doses. 揃oth primary liver cancer and metastatic disease of the liver are associate d with poor prognosis for patients, and new therapies are clearly needed,s aid Josep Tabernero, M.D., Chairman of the Medical Oncology Department and P hase I Program at Vall d扝ebron University Hospital in Barcelona, Spain. 揟h is Phase I trial and extension study with ALN-VSP represents, to our knowled ge, the most comprehensive clinical trial of a systemically delivered RNAi t herapeutic and also the most extensive experience with RNAi therapeutics in cancer. The safety data and anti-tumor activity with ALN-VSP, including a co mplete response in a patient with multiple liver metastases who had failed m ultiple prior therapies, are very encouraging and I look forward to the furt her development of this promising agent.br /> In 2012, Alnylam and Ascletis Pharmaceuticals (Hangzhou) Co., Ltd., a privat ely held U.S.-China joint venture pharmaceutical company, formed a strategic collaboration for the development of ALN-VSP in China. Alnylam will retain all rights in the rest of the world, and is eligible to receive milestones a nd royalties from Ascletis based on product sales. About Liver Cancers Cancer affecting the liver, known as either primary or secondary liver cance r, is associated with one of the poorest survival rates in oncology and repr esents a major unmet medical need affecting a large number of patients world wide. Primary liver cancer, or hepatocellular carcinoma (HCC), is one of the most common cancers worldwide, with more than 630,000 people diagnosed each year including approximately 350,000 in China. Secondary liver cancer, also known as metastatic liver cancer, is cancer that spreads to the liver from another part of the body due to other common cancers like colon, lung, or br east cancer. Worldwide, more than 500,000 people are diagnosed with secondar y liver cancer each year. About LNP Technology Alnylam has licenses to Tekmira LNP intellectual property for use in RNAi th erapeutic products using LNP technology. About RNA Interference (RNAi) RNAi (RNA interference) is a revolution in biology, representing a breakthro ugh in understanding how genes are turned on and off in cells, and a complet ely new approach to drug discovery and development. Its discovery has been h eralded as 揳 major scientific breakthrough that happens once every decade o r so,and represents one of the most promising and rapidly advancing fronti ers in biology and drug discovery today which was awarded the 2006 Nobel Pri ze for Physiology or Medicine. RNAi is a natural process of gene silencing t hat occurs in organisms ranging from plants to mammals. By harnessing the na tural biological process of RNAi occurring in our cells, the creation of a m ajor new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam抯 RNAi therapeutic platform, target the cause of diseases by potentl y 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 o n 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 therapeutic s for the treatment of genetically defined diseases, including ALN-TTR for t he treatment of transthyretin-mediated amyloidosis (ATTR), ALN-AT3 for the t reatment of hemophilia and rare bleeding disorders (RBD), ALN-AS1 for the tr eatment of acute intermittent porphyria, ALN-PCS for the treatment of hyperc holesterolemia, and ALN-TMP for the treatment of hemoglobinopathies. As part of its 揂lnylam 5x15TMstrategy, the company expects to have five RNAi the rapeutic products for genetically defined diseases in clinical development, including programs in advanced stages, on its own or with a partner by the e nd of 2015. Alnylam has additional partnered programs in clinical or develop ment stages, including ALN-RSV01 for the treatment of respiratory syncytial virus (RSV) infection and ALN-VSP for the treatment of liver cancers. The co mpany抯 leadership position on RNAi therapeutics and intellectual property h ave enabled it to form major alliances with leading companies including Merc k, Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko Kirin, Cubis t, Ascletis, Monsanto, and Genzyme. In addition, Alnylam holds a significant equity position in Regulus Therapeutics Inc., a company focused on discover y, development, and commercialization of microRNA therapeutics. Alnylam has also formed Alnylam Biotherapeutics, a division of the company focused on th e development of RNAi technologies for applications in biologics manufacturi ng, including recombinant proteins and monoclonal antibodies. Alnylam抯 Vaxi RNAplatform applies RNAi technology to improve the manufacturing processes for vaccines; GlaxoSmithKline is a collaborator in this effort. Alnylam sci entists and collaborators have published their research on RNAi therapeutics in over 100 peer-reviewed papers, including many in the world抯 top scienti fic journals such as Nature, Nature Medicine, Nature Biotechnology, and Cell . Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusett s. For more information, please visit www.alnylam.com. Alnylam Forward-Looking Statements Various statements in this release concerning Alnylam抯 future expectations, plans and prospects, including without limitation, statements regarding Aln ylam抯 views with respect to the potential for RNAi therapeutics, including the potential for ALN-VSP, and Alnylam抯 expectations regarding its 揂lnylam 5x15product strategy, constitute forward-looking statements for the purpo ses of the safe harbor provisions under The Private Securities Litigation Re form 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, Alnylam抯 ability to successfully demonstra te the efficacy and safety of its drug candidates and the pre-clinical and c linical results for these product candidates, including ALN-VSP, which may n ot support further development of such product candidates, both our and Ascl etisability to successfully advance ALN-VSP resulting in the potential pay ment of milestones and royalties to us, actions of regulatory agencies, whic h may affect the initiation, timing and progress of clinical trials for such product candidates, obtaining, maintaining and protecting intellectual prop erty, obtaining regulatory approval for products, competition from others us ing technology similar to Alnylam抯 and others developing products for simil ar uses, and Alnylam抯 ability to establish and maintain strategic business alliances, including its collaboration with Ascletis, and new business initi atives, as well as those risks more fully discussed in the 揜isk Factorsfi led with Alnylam抯 current report on Form 8-K filed with the Securities and Exchange Commission (SEC) on January 14, 2013 and in other filings that Alny lam makes with the SEC. In addition, any forward-looking statements represen t Alnylam抯 views only as of today and should not be relied upon as represen ting its views as of any subsequent date. Alnylam does not assume any obliga tion to update any forward-looking statements. Source: Alnylam Pharmaceuticals, Inc. Alnylam Pharmaceuticals, Inc. Cynthia Clayton, 617-551-8207 Vice President, Investor Relations and Corporate Communications or Spectrum Amanda Sellers, 202-955-6222 x2597 (Media) Home About Alnylam Leadership in RNAi Programs & Pipeline Intellectual Property Business Development News and Invest ors Capella Legal Site Map Copyright 2008 Alnylam Pharmaceuticals, Inc. All Rights Reserved
【在 t****r 的大作中提到】 : http://phx.corporate-ir.net/phoenix.zhtml?c=148005&p=irol-newsA : 9293&highlight= : 没那么夸张,只是phase I study 有效果而已。。。 : Alnylam and Collaborators Publish Results from Phase I Clinical Trial and Ex : tension Study with ALN-VSP, an RNAi Therapeutic for the Treatment of Liver C : ancer : - Results Published in Cancer Discovery Document Most Comprehensive Human Ex : perience To Date for RNAi Therapeutics Delivered with Lipid Nanoparticles (L : NPs) - : CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jan. 30, 2013-- Alnylam Pharmaceuticals,
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