Alnylam Completes ALN-VSP Phase I Trial in Patients with Liver Cancer

CAMBRIDGE, Mass.--(BUSINESS WIRE)--

Alnylam Pharmaceuticals, Inc. ALNY, a leading RNAi therapeutics company, announced today that it has completed its Phase I study with ALN-VSP, a systemically delivered RNAi therapeutic for the treatment of advanced solid tumors with liver involvement.

“We are very pleased with the results of our ALN-VSP Phase I trial that demonstrate safety and tolerability of multiple doses of ALN-VSP in addition to evidence for anti-tumor activity and proof of RNAi mechanism from tissue biopsy samples. Indeed, in this very advanced, heavily pre-treated cancer patient population, we have seen multiple patients achieve stable disease and one patient who has achieved a partial response with 70% tumor regression to date and who continues to receive drug after over one full year of treatment,” said Jared Gollob, M.D., Senior Director of Clinical Research at Alnylam. “These data are not only important for the continued clinical advancement of our ALN-VSP program, but they also significantly increase our confidence in our broader pipeline of systemically delivered RNAi therapeutics.”

In the Phase I study with ALN-VSP, 41 patients were enrolled and treated at doses ranging from 0.1 to 1.5 mg/kg. A total of 209 doses were administered, with a range of 1 to 28 doses per patient. Disease control (stable disease or better) was observed in 13 of 31 evaluable patients (42%) treated at doses of 0.4 to 1.5 mg/kg. The average duration of disease control is approximately five months, with a range of two to 14 months. Currently, five patients with disease control continue to receive ALN-VSP under an extension protocol; these include an endometrial cancer patient treated at 0.7 mg/kg with an ongoing partial response, as well as two renal cell cancer and two pancreatic neuroendocrine tumor patients treated at 1.0 mg/kg who have had stable disease for over four months.

“This Phase I study with ALN-VSP currently represents one of the most comprehensive clinical trials of a systemically delivered RNAi therapeutic, as well as one of the most extensive experiences with RNAi therapeutics in cancer,” said Geoffrey Shapiro, M.D., Ph.D., Associate Professor, Department of Medicine at Harvard Medical School; Director, Early Drug Development Center, and Associate Professor, Medical Oncology at Dana-Farber Cancer Institute. “Both primary liver cancer and metastatic disease of the liver are associated with poor prognosis for patients, and new therapies are clearly needed. Results from this study represent an important step in the development of a novel therapeutic strategy to treat this devastating disease.”

At the American Society of Clinical Oncology (ASCO) Annual Meeting in June 2011, Alnylam reported results from this trial which demonstrated that ALN-VSP was generally well tolerated, had single-agent anti-tumor activity, and showed RNAi-mediated target mRNA cleavage in both hepatic and extra-hepatic tumors. Disease control was achieved in one of 13 patients (8%) treated at doses less than or equal to 0.4 mg/kg versus 12 of 24 (50%) treated at doses greater than or equal to 0.7 mg/kg, including seven of 11 (64%) treated at the proposed Phase II dose of 1.0 mg/kg. A dose of 1.0 mg/kg administered every two weeks was identified as the regimen for further Phase II studies.

About ALN-VSP

ALN-VSP is a systemically delivered RNAi therapeutic comprising two siRNAs designed to target two genes critical for the growth and development of cancer cells: vascular endothelial growth factor (VEGF) and kinesin spindle protein (KSP), also known as eglin 5 (Eg5). ALN-VSP is Alnylam's first systemic RNAi program and represents the company's first clinical program in oncology. The company expects to partner its ALN-VSP program prior to initiating a Phase II clinical study.

About ALN-VSP Phase I Study Design

The Phase I trial was designed as a multi-center, open label, dose escalation study in patients with advanced solid tumors with liver involvement who have failed to respond to or have progressed after standard treatment. The primary objective was to evaluate the safety, tolerability, and pharmacokinetics of intravenous ALN-VSP. Other secondary and exploratory objectives included:

• assessment of tumor response using Response Evaluation Criteria for Solid Tumors (RECIST), a set of published guidelines that define when cancer patients' disease improves, stabilizes or progresses during treatment;
• quantitation of change in tumor blood flow and vascular permeability as measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI); and,
• analysis of pharmacodynamic effects of ALN-VSP on tumors as measured in patients electing to proceed with voluntary pre- and post-treatment biopsies.

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 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 “Alnylam 5x15^TM” 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 Huntington's disease. The company'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. 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 world'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 Alnylam's future expectations, plans and prospects, including without limitation, statements regarding Alnylam's views with respect to the potential for RNAi therapeutics, including ALN-VSP, its plan to partner its ALN-VSP program prior to initiating a Phase II clinical study, its views regarding the potential of other systemically delivered RNAi therapeutics, and Alnylam's expectations regarding its “Alnylam 5x15” product strategy, 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, Alnylam's ability to discover and develop novel delivery approaches and novel drug candidates, successfully demonstrate the efficacy and safety of its drug candidates, including ALN-VSP, in human clinical trials, and establish and maintain strategic business alliances, including a partnership for the continued development of ALN-VSP, and new business initiatives, as well as those risks more fully discussed in the “Risk Factors” section of its most recent annual 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.