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Alnylam Presents Preliminary Phase I Data at American Society of Clinical Oncology (ASCO) Meeting for ALN-VSP, an RNAi Therapeutic for the Treatment of Liver Cancers
- Study Results Demonstrate Tolerability, Pharmacokinetics, and Pharmacodynamic Effects, with Trial Continuing in Dose Escalation -

CHICAGO, Jun 07, 2010 (BUSINESS WIRE) --Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today preliminary clinical data from its ongoing Phase I trial with ALN-VSP, a systemically delivered RNAi therapeutic for the treatment of advanced solid tumors with liver involvement. The data are being presented at the ASCO meeting in a poster titled "Interim safety and pharmacodynamic results for ALN-VSP02, a novel RNAi therapeutic for solid tumors with liver involvement," in the Developmental Therapeutics - Experimental Therapeutics poster session being held from 8:00 a.m. to 12:00 p.m. CT in S Hall A2. The study results from the initial 19 patients in the first four dose cohorts demonstrate that ALN-VSP is well tolerated in most patients, and results from pharmacodynamic measurements provide preliminary evidence of clinical activity. The study has not yet reached a maximum tolerated dose and is continuing enrollment with dose escalation.

"Both primary liver cancer and metastatic disease of the liver are associated with poor prognosis for patients, and new therapies are clearly needed," said Josep Tabernero, M.D., Head of the Gastrointestinal Cancer and Phase I Program at Vall d'Hebron University Hospital in Barcelona, Spain. "The initial data with ALN-VSP are encouraging and we look forward to continued dose escalation to explore tolerability and potential for tumor response."

"The safety and tolerability of multiple doses of ALN-VSP demonstrated so far in these patients with advanced cancer and liver metastases are encouraging," said Charles Fuchs, M.D., M.P.H., Director for the Gastrointestinal Cancer Center at Dana-Farber Cancer Institute in Boston. "It is also notable that DCE-MRI results appear to show an anti-VEGF effect with ALN-VSP in the majority of these patients who have been previously exposed to multiple anti-VEGF and chemotherapy drugs. I look forward to seeing additional safety and pharmacodynamic data as dose escalation proceeds."

ALN-VSP is a systemically delivered RNAi therapeutic comprising two siRNAs designed to target two genes critical for the growth and survival of cancer cells: vascular endothelial growth factor (VEGF) and kinesin spindle protein (KSP), also known as eglin 5 (Eg5). The Phase I trial is a multi-center, open label, dose escalation study designed to enroll approximately 55 patients with advanced solid tumors with liver involvement who have failed to respond to or have progressed after standard treatment. The primary objective is to evaluate safety and tolerability of eight potential dose levels from 0.1 to 1.7 mg/kg. Secondary objectives include characterization of pharmacokinetics, and assessment of pharmacodynamic effects and tumor response through:

  • Response Evaluation Criteria for Solid Tumors (RECIST), a set of published guidelines that define when cancer patients' disease improves, stabilizes, or progresses during treatment;
  • change in tumor blood flow or vascular permeability as measured by Dynamic Contrast - Enhanced Magnetic Resonance Imaging (DCE-MRI);
  • change in plasma biomarkers of angiogenesis; and,
  • molecular and cellular analyses of tumor biopsy samples.

ALN-VSP was well-tolerated in most patients to date. A total of 62 doses have been administered to 19 patients receiving 0.1, 0.2, 0.4, or 0.7 mg/kg ALN-VSP. The majority of these patients had colorectal cancer, a primary tumor that often metastasizes to the liver. There were two mild acute infusion reactions at 0.4 and 0.7 mg/kg; both patients had no further reactions with slowing of the infusion and stayed on the trial. At 0.7 mg/kg, a patient with advanced pancreatic neuroendocrine cancer with extensive involvement of the liver developed hepatic failure five days following the second dose and subsequently died; this was deemed possibly related to study drug. Six additional patients treated at 0.7 mg/kg did not exhibit any evidence of hepatotoxicity. Maximum tolerated dose has not yet been reached and active enrollment is continuing.

Pharmacokinetic data showed that Cmax (peak serum concentration of drug) and area under the curve (AUC) were dose proportional with no evidence of drug accumulation. In addition, DCE-MRI results were suggestive of an anti-VEGF effect in the majority of treated patients. In 62% of evaluable liver tumors, there was a greater than 40% decline in Ktrans (measure of blood flow), an effect that is comparable to what has been observed with other anti-VEGF drugs in solid tumors (Cannistra et al., Journal of Clinical Oncology, 2006ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S, 2006; and Siegel et al., Journal of Clinical Oncology, Vol 26, No 18: pp. 2992-2998, 2008). Molecular and cellular analyses of biopsy samples are ongoing.

"We are encouraged by the results we have seen to date with ALN-VSP in this trial, which include tolerability data, as well as preliminary data on potential pharmacodynamic effects in this very advanced cancer patient population. The maximum tolerated dose has not yet been reached, and we continue to enroll patients in a dose-escalating manner," said Akshay Vaishnaw, M.D., Ph.D., Senior Vice President, Clinical Research at Alnylam. "We look forward to the further development of this promising agent and completion of this trial. Indeed, this is an important study that, to our knowledge, currently represents one of the most comprehensive clinical trials of systemically delivered RNAi therapeutics and also one of the most extensive experiences of RNAi therapeutics in cancer."

ALN-VSP is Alnylam's first systemic RNAi program and represents the company's first clinical program in oncology. The drug is formulated in a lipid nanoparticle developed by Tekmira Pharmaceuticals Corporation.

About Liver Cancers

Cancer affecting the liver, known as either primary or secondary liver cancer, is associated with one of the poorest survival rates in oncology and represents a major unmet medical need affecting a large number of patients worldwide. Primary liver cancer, or hepatocellular carcinoma (HCC), is one of the most common cancers worldwide, with more than 600,000 people diagnosed each year. 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 breast cancer. Worldwide, more than 500,000 people are diagnosed with secondary liver cancer each year.

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 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 for the treatment of a wide range of disease areas, including respiratory syncytial virus (RSV), liver cancers, TTR-mediated amyloidosis (ATTR), hypercholesterolemia, and Huntington's disease. In addition, Alnylam formed Alnylam Biotherapeutics, a division of the company focused on the development of RNAi technologies for application in manufacturing processes for biotherapeutic products, including recombinant proteins and monoclonal antibodies. 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 Kirin, and Cubist. Alnylam and Isis are joint owners of Regulus Therapeutics Inc., a company focused on the discovery, development, and commercialization of microRNA-based therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, please visit www.alnylam.com.

Alnylam Forward-Looking Statement

Various statements in this release concerning Alnylam's future expectations, plans and prospects, including without limitation, Alnylam's views with respect to the potential for RNAi therapeutics, including ALN-VSP, and its expectations with respect to the timing and success of its ongoing clinical trial of ALN-VSP, 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 Alnylam's ability to discover and develop novel drug candidates, such as ALN-VSP for the treatment of liver cancers, successfully demonstrate the efficacy and safety of ALN-VSP and other drug candidates in human clinical trials, 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.

SOURCE: Alnylam Pharmaceuticals, Inc.

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"Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: Statements in this press release regarding Alnylam Pharmaceuticals's business which are not historical facts are "forward-looking statements" that involve risks and uncertainties. For a discussion of such risks and uncertainties, which could cause actual results to differ from those contained in the forward-looking statements, see "Risk Factors" in the Company's Annual Report or Form 10-K for the most recently ended fiscal year.