Porphyria

We reported positive initial results from Cohorts 1 and 2 in Part C of our Phase 1 study with givosiran (gi-VOH-si-ran), the International Nonproprietary Name for ALN-AS1, an investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) for the treatment of acute hepatic porphyrias.  These results were presented at the 58th Annual Meeting of the American Society of Hematology (ASH), held December 3 – 6, 2016 in San Diego, California. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=1002501" type=" "]Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ASH-2016_Givosiran_Ph-1-Part-C_03Dec2016_CAPELLA.pdf" type="(470 KB PDF)"]View the presentation[/spotlight-link]

We reported interim results from our ongoing EXPLORE study, a multinational, prospective, observational study aimed at characterizing the natural history and clinical management of patients with acute hepatic porphyrias (AHP) who experience recurrent attacks or receive prophylactic treatment to prevent attacks.  Results from 112 patients, of which 104 have acute intermittent porphyria (AIP), showed a mean of 9.5 acute attacks reported in the prior year with severe neuropathic pain as the cardinal feature in 100% of attacks, along with other symptoms including nausea or vomiting (>80%), fatigue (77%), and weakness (79%).  Approximately 64% of patients reported experiencing porphyria symptoms between attacks, with about 46% experiencing symptoms daily.  Patients also reported a diminished quality of life and significant healthcare utilization, with a mean of 4.6 overnight hospitalizations per year (range 0-70) and a mean hospital stay duration of 6.6 days (range 1-60).  Of the attacks reported on study, approximately 76% of them required treatment with heme or at a healthcare facility. [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/EXPLORE-AASLD-Slides_11Nov16.pdf" type="(540 KB PDF)"] View the EXPLORE natural history presentation [/spotlight-link]

We presented interim results from our ongoing Phase 1 clinical trial with ALN-AS1, an investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) for the treatment of acute hepatic porphyrias (AHP), at the 2016 Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Symposium, held from September 6 – 9, 2016 in Rome, Italy. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=988112" type=" "]Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/SSIEM-2016_AS1_Ph1_Capella_Deck_090716.pdf" type="(840 KB PDF)"]View the presentation[/spotlight-link]

We reported positive initial results from our ongoing Phase 1 clinical trial with ALN-AS1, an investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) for the treatment of acute hepatic porphyrias. Study results showed that single subcutaneous doses of ALN-AS1 resulted in an up to 82% lowering of ALA and an up to 93% lowering of PBG in asymptomatic “high excreter” (ASHE) patients, who carry the genetic mutation of acute intermittent porphyria (AIP) and have elevated levels of aminolevulinic acid (ALA) and porphobilinogen (PBG), the toxic heme intermediates that mediate porphyria attacks. Furthermore, analysis of exosomal mRNA preparations from serum and urine revealed that treatment resulted in potent, dose-dependent, and durable silencing of liver ALAS1 mRNA.  Importantly, ALN-AS1 was found to be generally well tolerated with no clinically significant drug-related adverse events to date. These data provide human proof-of-concept for ALN-AS1 as a potential therapy for AIP and other acute hepatic porphyrias. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=931607" type=" "]Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ALN-AS1_ICPP_Interim-Ph1_09152015.pdf" type="(420 KB PDF)"]View the ALN-AS1 Phase 1 clinical data presentation[/spotlight-link]

On December 12, we hosted an R&D Day in New York City. Alnylam management and key opinion leaders discussed the latest progress as well as plans for the future development of our RNAi therapeutics pipeline. At this event, we announced our pipeline growth strategy for development and commercialization of RNAi therapeutics across three Strategic Therapeutic Areas (STArs): Genetic Medicines, Cardio-metabolic Disease, and Hepatic Infectious Disease. [spotlight-link icon="podcast" href="http://edge.media-server.com/m/p/njherf95" type=" "] Listen to the webcast replay[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/MASTER-RD-DAY-DECK_Capella.pdf" type="(12.3 MB PDF)"] View the complete presentation[/spotlight-link]

We presented new pre-clinical data supporting the selection of the ALN-AS1 Development Candidate for the treatment of hepatic porphyrias, including acute intermittent porphyria (AIP). The new research, presented at the 9th Annual Meeting of the Oligonucleotide Therapeutics Society, held October 6 – 8, 2013 in Naples, Italy, showed that multi-dose administration of a GalNAc-siRNA targeting ALAS-1 led to rapid, dose-dependent, and long-lasting knockdown of the ALAS-1 mRNA in non-human primates, with an ED50 of approximately 1.25 mg/kg.  Further, in a rat model of AIP, ALN-AS1 administration at doses as low as 2.5 mg/kg resulted in a complete blunting of phenobarbital-induced over-production of PBG and ALA, the toxic heme intermediates in AIP. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=795424" type=" "] Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ALNY-ALN-AS1update-OTS2013.pdf" type="(1.1 MB PDF)"] View our ALN-AS1 presentation [/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ALNY-ConjugateUpdate-OTS2013.pdf" type="(1.3 MB PDF)"] View our GalNAc-siRNA conjugate presentation [/spotlight-link]

On July 11, we hosted an R&D Day in New York City. Alnylam scientists and management reviewed progress with our Alnylam 5x15 pipeline for the development and commercialization of RNAi therapeutics. The event featured presentations by experts in the following disease areas: TTR-Mediated Amyloidosis, Hemophilia and Rare Bleeding Disorders, and Acute Intermittent Porphyria. [spotlight-link icon="podcast" href="http://investors.alnylam.com/eventdetail.cfm?eventid=131417" type=" "] Listen to the webcast replay[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/Alnylam-RDDayPres-Capella-July2013.pdf" type="(3.4 MB PDF)"] View the complete presentation[/spotlight-link] TTR-Mediated Amyloidosis [spotlight-link icon="podcast" href="http://www.alnylam.com/web/assets/RDday-2013/alnylam_podcast_RDDay-ATTRAmyloidosisOverview-July2013.mp3" type="(24.7 MP3)"] Listen to Dr. Philip Hawkins discuss TTR-Mediated Amyloidosis[/spotlight-link][spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/RDday-2013/Alnylam-RDDay-ATTRAmyloidosisOverview-July2013.pdf" type="(1.8 MB PDF)"] View the presentation[/spotlight-link][spotlight-link icon="podcast" href="http://www.alnylam.com/web/assets/RDday-2013/alnylam_podcast_RDDay-ALN-TTR-ProgramOverview-July2013.mp3" type="(25.4 MP3)"] Listen to the ALN-TTR program overview[/spotlight-link][spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/RDday-2013/Alnylam-RDDay-ALN-TTR-ProgramOverview-July2013.pdf" type="(0.6 MB PDF)"] View the presentation[/spotlight-link] Hemophilia and Rare Bleeding Disorders (RBD) [spotlight-link icon="podcast" href="http://www.alnylam.com/web/assets/RDday-2013/alnylam_podcast_RDDay-HemophiliaAndRDBsOverview-July2013.mp3" type="(28.6 MP3)"] Listen to Dr. Craig Kessler discuss Hemophilia and RBDs[/spotlight-link][spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/RDday-2013/Alnylam-RDDay-HemophiliaAndRDBsOverview-July2013.pdf" type="(0.8 MB PDF)"] View the presentation[/spotlight-link]

We presented pre-clinical proof-of-concept data from our ALN-AS1 program for the treatment of acute intermittent porphyria (AIP) at the International Congress of Porphyrins and Porphyrias being held May 16 – 18, 2013. The research, presented by Alnylam scientists and collaborators at the Icahn School of Medicine at Mount Sinai in New York City, showed that administration of a GalNAc-conjugated siRNA targeting aminolevulinate synthase-1 (ALAS-1) blocked production of aminolevulinic acid (ALA) and porphobilinogen (PBG), the toxic precursors that cause disease symptoms and pathophysiology, in a mouse model of AIP. [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ALNY-Porphyria-AS1-Pres-May17-2013.pdf" type="(1.6 MB PDF)"] View our presentation [/spotlight-link] [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=765697" type=" "] Read our press release[/spotlight-link]

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