Alnylam Reports Positive Initial Results from Ongoing Phase 1/2 Study of ALN-GO1, an Investigational RNAi Therapeutic for the Treatment of Primary Hyperoxaluria Type 1

Sep 24,2016

- ALN-GO1 Achieves Human Proof of Concept with Statistically Significant Increases in Glycolate, a Biomarker of Effective Glycolate Oxidase Knockdown, in Healthy Adult Volunteers -

- Single Doses of ALN-GO1 Found to be Generally Well Tolerated -

- Company to Discuss Clinical Data during ALN-GO1 RNAi Roundtable on Tuesday, September 27 at 10:00 a.m. ET -

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today initial data from its ongoing Phase 1/2 study with ALN-GO1, an investigational RNAi therapeutic targeting glycolate oxidase (GO) for the treatment of Primary Hyperoxaluria Type 1 (PH1). Initial clinical results were presented today during an oral presentation at the 17th Congress of the International Pediatric Nephrology Association (IPNA), being held September 20 - 24, 2016 in Iguaçu, Brazil. These data were from Part A of the ongoing Phase 1/2 study, which is being conducted in healthy adult volunteers. Results showed that single, subcutaneous doses of ALN-GO1 achieved dose-dependent increases in plasma and urine glycolate. Glycolate is the substrate used by the GO enzyme to produce excessive oxalate in patients with PH1; thus, increases in plasma and urine glycolate in normal volunteers confirm effective GO knockdown and provide preliminary human proof of concept for ALN-GO1. Further, ALN-GO1 was found to be generally well tolerated, with no serious adverse events (SAEs) reported through the safety data transfer date. The Company plans to soon transition to Part B of the Phase 1/2 study, which will evaluate multiple doses of ALN-GO1 in patients with PH1.

"We believe ALN-GO1 has the potential to be a transformative therapy for patients with PH1, a potentially fatal and ultra-rare orphan disease that primarily afflicts children. The current treatment approach for patients suffering from this condition is routine dialysis and, ultimately, a dual liver and kidney transplant, as no approved pharmaceutical options currently exist," said Akshay Vaishnaw, M.D., Ph.D., Executive Vice President of R&D and Chief Medical Officer at Alnylam. "We believe these initial results are encouraging, as they demonstrate preliminary human proof of concept for this novel investigational RNAi therapeutic. We now look forward to advancing this program into patients in Part B of the ongoing Phase 1/2 study, where we aim to achieve lowering of urinary oxalate, which is known to deposit in kidneys and cause extensive renal and broader tissue damage in patients with PH1."

Initial results include all available data as of the data transfer dates on August 17, 2016 (for safety) and September 2, 2016 (for pharmacodynamic activity). Subjects in Part A (N=32) were enrolled in four single ascending dose cohorts (N=8 per group, randomized 3:1 drug:placebo), with subjects receiving ALN-GO1 at doses ranging from 0.3 to 6.0 mg/kg. ALN-GO1 administration resulted in dose-dependent and statistically significant (nominal two-sided p values less than 0.05) increases from baseline in plasma and urinary glycolate as compared to placebo, with up to an 8-fold increase in plasma glycolate in the highest dose cohort. Based on extrapolation from pre-clinical studies, the observed level of glycolate increase would correlate with an estimated greater than 80% silencing of the HAO1 mRNA, the transcript of the GO enzyme. The effects of ALN-GO1 were highly durable, with levels sustained through 85 days at the highest dose, supportive of a once-monthly and possibly once-quarterly subcutaneous dose regimen.

Single doses of ALN-GO1 were shown to be generally well tolerated in healthy adult volunteers. There were no SAEs reported. Adverse events (AEs) were reported in 88% (N=21) of ALN-GO1 treated subjects and 63% (N=5) of placebo treated subjects. Common AEs occurring in greater than 10% of ALN-GO1 treated subjects included nasopharyngitis (N=6), headache (N=5), and transient injection site pain (N=4). All AEs were mild to moderate with the exception of one subject in the lowest dose cohort who had transient, asymptomatic CPK elevation which was unrelated to study drug.

To view the ALN-GO1 clinical data described in this press release, please visit

ALN-GO1 RNAi Roundtable Webinar Information
Alnylam will review these initial clinical data and discuss PH1 and plans for the further development of ALN-GO1 in an RNAi Roundtable webinar this Tuesday, September 27, 2016 at 10:00 a.m. ET. Speakers include:

  • Barry Greene, President
  • David Erbe, Ph.D., Director, Research
  • Guest Speaker: Sally-Anne Hulton, M.D., FRCPCH, MRCP, FCP, MBBCh, Consultant Paediatric Nephrologist and Clinical Lead, Birmingham Children's Hospital NHS Trust
  • Guest Speaker: Jennifer Lawrence, M.D. (mother of a PH1 patient)

To register for the webinar, please visit A replay of the webinar and downloadable PDF of the presentation will be available on that website shortly after the Roundtable.

About the ALN-GO1 Phase 1/2 Study
The Phase 1/2 trial of ALN-GO1 is a randomized, single-blind, placebo-controlled study being conducted in two parts. Part A is a single-dose study that enrolled 32 healthy adult volunteers. Part B will be a multi-dose study designed to enroll up to a total of 20 patients with PH1. The primary objective of the study is to evaluate safety and tolerability of single and multiple subcutaneous doses of ALN-GO1. Secondary objectives include evaluation of pharmacokinetics and clinical activity for ALN-GO1 as measured by its effects on plasma glycolate and urinary oxalate levels in normal healthy volunteers and PH1 patients, respectively.

About Primary Hyperoxaluria Type 1 (PH1) and ALN-GO1
PH1 is an inborn error of metabolism. Specifically, PH1 is an autosomal recessive disorder of glyoxylate metabolism, where hepatic detoxification of glyoxylate is impaired due to mutation of the AGXT gene - which encodes the liver peroxisomal alanine-glyoxylate aminotransferase (AGT) enzyme - resulting in excessive oxalate production. Excess oxalate in PH1 patients results in the deposition of calcium oxalate crystals in the kidneys and urinary tract and can lead to the formation of recurrent kidney stones or nephrocalcinosis. Renal damage is caused by a combination of tubular toxicity from oxalate, calcium oxalate deposition in the kidneys, and urinary obstruction by calcium oxalate stones. Compromised kidney function exacerbates the disease as the excess oxalate can no longer be excreted, potentially resulting in subsequent accumulation and crystallization in bones, eyes, skin, and heart, leading to severe illness and death. About 50 percent of patients will have kidney failure by age 15, and about 80 percent will have end stage renal disease by age 30. Current treatment options are very limited, and include frequent renal dialysis or combined organ transplantation of liver and kidneys, a procedure with high morbidity that is limited due to organ availability. Although a small minority of patients respond to Vitamin B6 supplementation, there are no approved pharmaceutical therapies for PH1.

ALN-GO1 is an investigational RNAi therapeutic, currently in early stage clinical development. The safety and efficacy of ALN-GO1 have not been evaluated by the U.S. Food and Drug Administration or any other health authority.

Sanofi Genzyme Alliance
In January 2014, Alnylam and Sanofi Genzyme, the specialty care global business unit of Sanofi, 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 Sanofi Genzyme obtained the right to access certain programs in Alnylam's current and future Genetic Medicines pipeline, including ALN-GO1, in the rest of the world (ROW) through the end of 2019, together with certain broader co-development/co-commercialization rights and global product rights for certain products, including ALN-GO1.

About GalNAc Conjugates and Enhanced Stabilization Chemistry (ESC)-GalNAc Conjugates
GalNAc-siRNA conjugates are a proprietary Alnylam delivery platform and are designed to achieve targeted delivery of RNAi therapeutics to hepatocytes through uptake by the asialoglycoprotein receptor. Alnylam's Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate technology enables subcutaneous dosing with increased potency and durability, and a wide therapeutic index. This delivery platform is being employed in nearly all of Alnylam's pipeline programs, including programs in clinical development.

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 Ionis, Novartis, Roche, Takeda, Merck, Monsanto, The Medicines Company, and Sanofi Genzyme. 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

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 investigational RNAi therapeutics, including ALN-GO1, its expectations regarding the timing of clinical studies and the expected timing for the presentation of clinical data from these studies, including from Part B of the ongoing Phase 1/2 study of ALN-GO1, its expectations regarding its STAr pipeline growth strategy, and its plans regarding commercialization of RNAi therapeutics, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other 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 product 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 for a specified indication or at all, actions or advice of regulatory agencies, which may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional pre-clinical and/or clinical testing, delays, interruptions or failures in the manufacture and supply of our product candidates, obtaining, maintaining and protecting intellectual property, Alnylam's ability to enforce its intellectual property rights against third parties and defend its patent portfolio against challenges from third parties, obtaining and maintaining regulatory approval, pricing and reimbursement for products, progress in establishing a commercial and ex-United States infrastructure, competition from others using technology similar to Alnylam's and others developing products for similar uses, Alnylam's ability to manage its growth and operating expenses, 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 and distribution of products, the outcome of litigation, the risk of government investigations, 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, except to the extent required by law, to update any forward-looking statements.

The scientific information discussed in this news release relating to Alnylam's investigational therapeutic, ALN-GO1, is preliminary and investigative. ALN-GO1 has not been approved by the U.S. Food and Drug Administration, European Medicines Agency, or any other regulatory authority and no conclusions can or should be drawn regarding the safety or effectiveness of ALN-GO1.

Alnylam Pharmaceuticals, Inc.
(Investors and Media)
Christine Regan Lindenboom, 617-682-4340
Josh Brodsky, 617-551-8276

Source: Alnylam Pharmaceuticals, Inc.

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