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Alnylam Reports Positive Interim Results from Ongoing Phase 1 Study of ALN-AS1, an Investigational RNAi Therapeutic for the Treatment of Acute Hepatic Porphyrias
Sept. 7, 2016 8:20 a.m. ET
-- In Asymptomatic High Excreter (ASHE) Porphyria Subjects, Single and Multiple Doses of ALN-AS1 Achieve Rapid, Dose-Dependent, and Durable Lowering of Toxic Heme Synthesis Intermediates, with Effects Sustained for Over Ten Months After a Single Dose --

-- ALN-AS1 Generally Well Tolerated Following Single and Multiple Doses --

-- ALN-AS1 Granted Orphan Drug Designation for the Treatment of Acute Hepatic Porphyrias by the United States Food and Drug Administration --

-- Company to Discuss New Clinical Data during ALN-AS1 RNAi Roundtable on Tuesday, September 13 at 11:30 a.m. ET --

CAMBRIDGE, Mass.--(BUSINESS WIRE)--September 07, 2016--
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today interim data from its ongoing Phase 1 study with ALN-AS1, an investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) for the treatment of acute hepatic porphyrias. These results were presented today during an oral presentation at the 2016 Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Symposium, being held from September 6 -- 9, 2016 in Rome, Italy. The new data were from Parts A and B of the ongoing Phase 1 study, which were conducted in asymptomatic "high excreter" (ASHE) subjects. ASHE subjects have a mutation in the porphobilinogen deaminase (PBGD) gene as found in acute intermittent porphyria (AIP) and have elevated levels of upstream toxic heme intermediates aminolevulinic acid (ALA) and porphobilinogen (PBG) that mediate porphyria attacks. Results demonstrated that single and once-monthly, subcutaneous administration of ALN-AS1 achieved rapid, dose-dependent, and durable lowering of ALA and PBG. Further, ALN-AS1 was found to be generally well tolerated. Alnylam is currently conducting Part C of the Phase 1 study in symptomatic AIP patients with recurrent porphyria attacks. Consistent with previous guidance, the Company plans to present initial porphyria biomarker data from Part C in late 2016, with potential clinical efficacy data on the frequency and severity of recurrent attacks expected in 2017.

"The acute hepatic porphyrias are a group of ultra-rare orphan diseases with enormous unmet medical need, where novel therapies are clearly warranted. Accordingly, we're very encouraged by these interim Phase 1 data in ASHE subjects, showing robust lowering of the toxic heme synthesis intermediates that mediate porphyria attacks," said Akshay Vaishnaw, M.D., Ph.D., Executive Vice President of Research and Chief Medical Officer at Alnylam. "We also continue to be impressed by the durability of effect on these disease biomarkers following a single subcutaneous injection, which we believe to be supportive of a monthly or potentially once quarterly low volume dosing regimen. Importantly, ALN-AS1 has been generally well tolerated through the data transfer date. We very much look forward to the continued advancement of this novel compound, including initial data in symptomatic AIP patients with recurring porphyria attacks expected later this year."

New results include all available data as of the data transfer date of June 28, 2016. In Part A (N=20), subjects were enrolled in five single ascending dose (SAD) cohorts (N=4 per group, randomized 3:1, drug:placebo), receiving ALN-AS1 at doses from 0.035 to 2.5 mg/kg. In Part B (N=8), subjects were enrolled in two multiple ascending dose (MAD) cohorts (N=4 per group, randomized 3:1, drug:placebo), receiving two monthly subcutaneous doses of ALN-AS1 at 0.35 or 1.0 mg/kg. In both Parts A and B, ALN-AS1 administration resulted in rapid, dose-dependent, and durable silencing of liver ALAS1 mRNA. In addition, ALN-AS1 resulted in rapid and dose-dependent lowering of ALA and PBG of up to 95%. Reductions in ALA and PBG were highly durable, with effects lasting for over ten months after a single dose.

As of the data transfer date, ALN-AS1 continued to be generally well tolerated in ASHE subjects following single and multiple doses. There were three serious adverse events (SAEs) that were all deemed to be unlikely related to study drug. A total of 78 adverse events (AEs) were reported in both the SAD and MAD cohorts, of which 62 were determined to be not related or unlikely related to ALN-AS1 administration. With the exception of one AE, not related to study drug, that was severe, all other AEs were mild or moderate in severity, and most commonly included abdominal pain, diarrhea, hypoesthesia, nasopharyngitis, pruritis, and rash. Two mild and transient injection site reactions (ISRs) were reported. There were no clinically significant changes in vital signs, electrocardiograms, clinical laboratory parameters, or physical examination.

To view the ALN-AS1 clinical data described in this press release, please visit

Alnylam also announced today that the United States Food and Drug Administration (FDA) has granted Orphan Drug Designation to ALN-AS1 for the treatment of acute hepatic porphyrias. The FDA Office of Orphan Products Development (OOPD) mission is to advance the evaluation and development of products that demonstrate promise for the diagnosis and/or treatment of rare diseases or conditions. The Orphan Drug Act provides incentives for sponsors to develop products for rare diseases. In July 2016, the European Medicines Agency (EMA) granted Orphan Drug Designation to ALN-AS1 for the treatment of acute hepatic porphyrias.
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