Alnylam Initiates Phase 3 Open Label Extension Study ("APOLLO-OLE") with Patisiran, an Investigational RNAi Therapeutic Targeting Transthyretin (TTR) for the Treatment of TTR-Mediated Amyloidosis (ATTR Amyloidosis)

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

Alnylam Pharmaceuticals, Inc. ALNY, a leading RNAi therapeutics company, announced today that it has initiated its Phase 3 open-label extension study (abbreviated "APOLLO-OLE") with patisiran, an investigational RNAi therapeutic targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR amyloidosis) in patients with Familial Amyloidotic Polyneuropthy (FAP). All patients who complete the APOLLO Phase 3 trial with patisiran are eligible to enroll in APOLLO-OLE. The study will evaluate the long-term safety and efficacy of patisiran and will also measure effects of treatment toward a number of clinical endpoints, including the modified Neuropathy Impairment Score, or "mNIS+7," which is an evaluation of muscle weakness, sensory and autonomic function, and nerve conductance. The company is also reiterating its previous guidance that – assuming positive study results in the APOLLO Phase 3 study – it expects to be in a position to file a New Drug Application (NDA) for patisiran in the 2017 timeframe.

"Patisiran is the leading investigational candidate in our pipeline of RNAi therapeutics. We are very encouraged with the clinical activity and tolerability seen to date with patisiran, including in our Phase 2 OLE study where we have recently reported what we believe to be continued evidence for a possible halting of neuropathy progression after the first 12 months of treatment," said Akshay Vaishnaw, M.D., Ph.D., Executive Vice President of R&D and Chief Medical Officer of Alnylam. "The initiation of APOLLO-OLE marks our continued progress with patisiran, and we are pleased to provide patients previously treated in APOLLO with the opportunity to receive patisiran on an ongoing basis. The APOLLO trial continues enrolling patients with FAP, and, assuming positive results, we expect to be in a position to file an NDA in the 2017 timeframe. Accordingly, we believe successful execution of the APOLLO Phase 3 trial is a critical step toward achieving our ‘Alnylam 2020' goals where, by the end of 2020, we expect to have 3 marketed products, as well as 10 programs in clinical development, including 4 in late stages of development, across our 3 Strategic Therapeutic Areas, or ‘STArs.'"

"Therapeutic options for ATTR amyloidosis patients with FAP are limited, and there is a significant need for novel therapies to treat this debilitating disease. I am pleased with Alnylam's progress to date with patisiran, and find the recent Phase 2 OLE data to be very encouraging. In particular, the possibility of halting neuropathic progression over 12 months of treatment is promising in light of the rapid increase in neuropathy impairment scores observed in analysis of other historical data sets," said Juan Buades, M.D., Ph.D., Internal Medicine Specialist, and Head of the TTR-FAP Clinic, Hospital Son Llatzer, Palma de Mallorca, Spain. "I very much look forward to continuing to participate in the clinical advancement of this investigational medicine."

APOLLO-OLE is an open-label, multi-center study designed to evaluate the long-term safety and tolerability of patisiran in ATTR amyloidosis patients with FAP who were previously enrolled in the APOLLO Phase 3 study. Eligible patients treated in APOLLO can enroll in the study, where they will receive patisiran at a dose of 0.3 mg/kg every three weeks for up to the earlier of two years or until the drug is commercially available in their market. The primary objective of APOLLO-OLE is to evaluate the long-term safety and efficacy of patisiran administration. The study will measure a number of clinical endpoints, including Neuropathy Impairment Score at baseline and every 12 months thereafter. A number of additional clinical endpoints will be assessed, including: quality of life; timed 10-meter walk test to evaluate mobility; modified body mass index as a measure of nutritional status; level of disability; and nerve fiber density in skin biopsies.

In addition to the APOLLO and APOLLO-OLE trials, Alnylam is also currently conducting a Phase 2 OLE study, where patients previously treated in a Phase 2 study are receiving open-label patisiran at a dose of 0.3 mg/kg every 3 weeks. Initial 12-month clinical data from this study were presented recently at the 67th Annual Meeting of the American Academy of Neurology (AAN) held April 18 – 25, 2015. Patisiran was found to be generally well tolerated out to 17 months of drug administration, with no drug-related serious adverse events to date. In addition, patisiran treatment achieved a sustained mean serum TTR knockdown at the 80% target level for approximately 16 months, with an up to 88% mean knockdown achieved between doses. Results of neuropathy assessments showed a mean 2.5 point decrease in mNIS+7 at 12 months in patients (N=20) who had reached the 12-month endpoint at the time of data cutoff. This decrease in neuropathy progression compares favorably to the 13 to 18 point increase in mNIS+7 at 12 months that can be estimated from the literature in untreated FAP patients with similar baseline characteristics. In aggregate, these results are consistent with the therapeutic hypothesis that TTR knockdown has the potential to halt neuropathy progression in patients with FAP. Alnylam plans to report complete 12-month data (N=27) and preliminary 18-month data from the patisiran Phase 2 OLE study in late 2015.

Genzyme Alliance

In January 2014, Alnylam and Genzyme, a Sanofi company, formed an alliance to accelerate and expand the development and commercialization of RNAi therapeutics across the world. The alliance is structured as a multi-product geographic alliance in the field of rare diseases. Alnylam retains product rights in North America and Western Europe, while Genzyme obtained the right to access certain programs in Alnylam's current and future Genetic Medicines pipeline in the rest of the world (ROW), including co-development/co-commercialization and/or global product rights in certain defined instances. In the case of patisiran, Alnylam will advance the product in North America and Western Europe, while Genzyme will advance the product in the ROW.

About Transthyretin-Mediated Amyloidosis

Transthyretin (TTR)-mediated amyloidosis (ATTR) is an inherited, progressively debilitating, and often fatal disease caused by mutations in the TTR gene. TTR protein is produced primarily in the liver and is normally a carrier of vitamin A. Mutations in TTR cause abnormal amyloid proteins to accumulate and damage body organs and tissue, such as the peripheral nerves and heart, resulting in intractable peripheral sensory neuropathy, autonomic neuropathy, and/or cardiomyopathy. ATTR represents a major unmet medical need with significant morbidity and mortality; familial amyloidotic polyneuropathy (FAP) affects approximately 10,000 people worldwide and familial amyloidotic cardiomyopathy (FAC) is estimated to affect at least 40,000 people worldwide. FAP patients have a life expectancy of 5 to 15 years from symptom onset, and the only approved treatment options for early stage disease are liver transplantation, and tafamidis (approved in Europe). FAC is fatal within 2.5 to 5 years of diagnosis and treatment is currently limited to supportive care. Senile systemic amyloidosis (SSA) is a non-hereditary form of TTR cardiac amyloidosis caused by idiopathic deposition of wild-type TTR; its prevalence is generally unknown, but is associated with advanced age. There is a significant need for novel therapeutics to treat patients with TTR amyloid polyneuropathy and/or cardiomyopathy.

About LNP Technology

Alnylam has licenses to Tekmira LNP intellectual property for use in RNAi therapeutic products using LNP technology.

About 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 RNA (siRNA), 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. Alnylam's pipeline of investigational RNAi therapeutics is focused in 3 Strategic Therapeutic Areas (STArs): Genetic Medicines, with a broad pipeline of RNAi therapeutics for the treatment of rare diseases; Cardio-Metabolic Disease, with a pipeline of RNAi therapeutics toward genetically validated, liver-expressed disease targets for unmet needs in cardiovascular and metabolic diseases; and Hepatic Infectious Disease, with a pipeline of RNAi therapeutics that address the major global health challenges of hepatic infectious diseases. In early 2015, Alnylam launched its "Alnylam 2020" guidance for the advancement and commercialization of RNAi therapeutics as a whole new class of innovative medicines. Specifically, by the end of 2020, Alnylam expects to achieve a company profile with 3 marketed products, 10 RNAi therapeutic clinical programs – including 4 in late stages of development – across its 3 STArs. The company's demonstrated commitment to RNAi therapeutics has enabled it to form major alliances with leading companies including Merck, Medtronic, Novartis, Biogen, Roche, Takeda, Kyowa Hakko Kirin, Cubist, GlaxoSmithKline, Ascletis, Monsanto, The Medicines Company, and Genzyme, a Sanofi company. In addition, Alnylam holds an equity position in Regulus Therapeutics Inc., a company focused on discovery, development, and commercialization of microRNA therapeutics. Alnylam scientists and collaborators have published their research on RNAi therapeutics in over 200 peer-reviewed papers, including many in the world's top scientific journals such as Nature, Nature Medicine, Nature Biotechnology, Cell, New England Journal of Medicine, and The Lancet. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information about Alnylam's pipeline of investigational RNAi therapeutics, 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, Alnylam's views with respect to the potential for RNAi therapeutics, including patisiran for the treatment of ATTR amyloidosis in patients with FAP, expectations regarding the reporting of data from clinical studies, in particular the ongoing Phase 2 OLE study with patisiran, expectations regarding the filing of a New Drug Application and/or foreign equivalent for patisiran, expectations regarding its STAr pipeline growth strategy, and its plans regarding commercialization of RNAi therapeutics, including patisiran, 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 drug candidates and delivery approaches, successfully demonstrate the efficacy and safety of its drug candidates, the pre-clinical and clinical results for its product candidates, which may not be replicated or continue to occur in other subjects or in additional studies or otherwise support further development of product candidates, actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials, obtaining, maintaining and protecting intellectual property, Alnylam's ability to enforce its patents against infringers and defend its patent portfolio against challenges from third parties, obtaining regulatory approval for products, competition from others using technology similar to Alnylam's and others developing products for similar uses, Alnylam's ability to manage operating expenses, Alnylam's ability to obtain additional funding to support its business activities and establish and maintain strategic business alliances and new business initiatives, Alnylam's dependence on third parties for development, manufacture, marketing, sales and distribution of products, the outcome of litigation, and unexpected expenditures, as well as those risks more fully discussed in the "Risk Factors" filed with Alnylam's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in other filings that Alnylam makes with the SEC. 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 explicitly disclaims any obligation to update any forward-looking statements.

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