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Alnylam welcomes you to Capella, the destination for updates on our progress in translating the science of RNAi toward innovative medicines.

Initial Data in Paroxysmal Nocturnal Hemoglobinuria Patients from Ongoing Phase 1/2 Clinical Study with ALN-CC5 Support Potential for Eculizumab Sparing and Improved Disease Control for Eculizumab Inadequate Responders

June 11, 2016

Initial Data in Paroxysmal Nocturnal Hemoglobinuria Patients from Ongoing Phase 1/2 Clinical Study with ALN-CC5 Support Potential for Eculizumab Sparing and Improved Disease Control for Eculizumab Inadequate Responders

We reported data from 6 patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) enrolled in Part C of our ongoing Phase 1/2 clinical study with ALN-CC5, an investigational RNAi therapeutic targeting complement component 5 (C5) for the treatment of complement-mediated diseases. These data were presented at the 21st Congress of the European Hematology Association (EHA) Meeting in Copenhagen, Denmark, held June 9-12, 2016.  In this part of the study, ALN-CC5 was evaluated as a monotherapy or as an adjunct to eculizumab, an approved anti-C5 monoclonal antibody indicated for the treatment of PNH.



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Updated Healthy Volunteer Data from Phase 1/2 Clinical Study with ALN-CC5 for the Treatment of Complement-Mediated Diseases

May 22, 2016

Updated Healthy Volunteer Data from Phase 1/2 Clinical Study with ALN-CC5 for the Treatment of Complement-Mediated Diseases

We reported updated data from our ongoing Phase 1/2 clinical study with ALN-CC5, an investigational RNAi therapeutic targeting complement component C5 for the treatment of complement-mediated diseases. Data were presented at the 53rd Congress of the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) in Vienna, Austria, held May 21-24, 2016.  Results showed that administration of ALN-CC5 in healthy volunteers (N=44) achieved up to 99% knockdown of serum C5 and a mean maximum of 86% serum hemolysis inhibition in the highest dose group, with mean levels consistently greater than 80% inhibition through the 13 weeks of treatment. Results also showed a mean maximum CH50 inhibition of 99.6% and maximum inhibition up to 100% relative to baseline.

The effects of ALN-CC5 were found to be highly durable, with C5 knockdown clamped at over 90% for more than six months following a single dose. C5 knockdown and complement inhibition results support the potential for a once-quarterly dosing regimen when used in combination with the monoclonal antibody, eculizumab. Importantly, ALN-CC5 was shown to be generally well tolerated, with no serious adverse events and no drug-related discontinuations to date. All adverse events were mild or moderate in severity.


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Complete 18-Month Data from Ongoing Phase 2 OLE Study with Patisiran in Development for the Treatment of Hereditary TTR-Mediated Amyloidosis with Polyneuropathy (hATTR-PN)

April 20, 2016

Complete 18-Month Data from Ongoing Phase 2 OLE Study with Patisiran in Development for the Treatment of Hereditary TTR-Mediated Amyloidosis with Polyneuropathy (hATTR-PN)

We reported results from our ongoing Phase 2 open-label extension (OLE) study with patisiran at the 68th Annual Meeting of the American Academy of Neurology (AAN), held April 15 – 21, 2016 in Vancouver, British Columbia, Canada.  Complete 18-month data (N=27) from the study provided continued evidence that patisiran has the potential to halt neuropathy progression in patients with hATTR-PN (also known as familial amyloidotic polyneuropathy, or FAP), showing a mean 0.8-point decrease in mNIS+7, which compares favorably to an estimated increase in mNIS+7 of 22 to 26 points at 18 months based upon analysis of historical data sets in untreated hATTR-PN patients with similar baseline neurologic impairment. Patisiran administration was also associated with a statistically significant, approximately 77% median improvement in nerve fiber density as read histologically in a blinded manner from distal thigh sweat gland biopsy samples.

Further, in the first reported exploratory analysis of its kind, the degree of TTR knockdown observed in patients was shown to correlate with improvement in mNIS+7 scores, supporting the therapeutic hypothesis that reduction of mutant and wild-type TTR may be associated with potential halting of neuropathy progression in patients with hATTR-PN.

Importantly, patisiran was found to be generally well tolerated out to 25 months of treatment.  There were no drug-related severe adverse events (SAEs), and the majority of reported adverse events (AEs) were mild to moderate.  The most common drug-related or possibly drug-related AEs were flushing (22.2%) and infusion-related reactions, or “IRRs” (18.5%). All IRRs and drug-related flushing AEs were mild in severity and did not result in any discontinuations.  In addition, there were no clinically significant changes in liver function tests, renal function tests, or other laboratory or hematologic parameters, including platelets.



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New Program Added to Genetic Medicines Pipeline: ALN-F12

March 7, 2016

New Program Added to Genetic Medicines Pipeline: ALN-F12

We’re announcing the addition of a new program to our genetic medicines pipeline, ALN-F12, an investigational RNAi therapeutic targeting F12 for the treatment of Hereditary Angioedema (HAE). Pre-clinical data for ALN-F12 were presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual meeting, held March 4-7, 2016.

HAE is a genetic disorder characterized by episodes of severe swelling in various parts of the body, including the face, hands, feet, gastrointestinal tract, and airways. It is caused by a defect in the C1-inhibitor gene that results in poor control of contact pathway activation and excessive bradykinin generation. Elevated levels of bradykinin increase vascular permeability, ultimately causing the episodic swelling attacks that are characteristic of HAE. The F12 gene encodes Factor XII (FXII), which is at the top of the contact pathway cascade. Pre-clinical data showed that administration of ALN-F12 resulted in dose-dependent reduction of vascular permeability in two different mouse models of bradykinin-driven vascular leakage, demonstrating that suppression of F12 mRNA has the potential to mitigate excess bradykinin stimulation. Further, in non-human primates, a single subcutaneous dose of ALN-F12 at 3 mg/kg resulted in potent and durable knockdown of serum FXII of greater than 85 percent, with knockdown of over 50 percent sustained out to three months following administration.


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Alnylam Supports Bleeding Disorders Month and World Hemophilia Day

February 28, 2016

Alnylam Supports Bleeding Disorders Month and World Hemophilia Day

“Bleeding Disorders Awareness Month,” was recently approved by the U.S. Department of Health and Human Services (HHS) as a National Health Observance in March. In previous years, March was dedicated to Hemophilia Awareness but through this new initiative, it has been expanded to unite the community and raise awareness of all inherited bleeding disorders and their potential health problems.

Alnylam Presentation at 34th Annual J.P. Morgan Healthcare Conference

January 11, 2016

Alnylam Presentation at 34th Annual J.P. Morgan Healthcare Conference

On Monday, January 11, 2016, John Maraganore presented an updated company overview at the 34th Annual J.P. Morgan Healthcare Conference in San Francisco. You may access the presentation below.


Path to “Alnylam 2020” Presented at R&D Day 2015

December 10, 2015

Path to “Alnylam 2020” Presented at R&D Day 2015

On December 10, 2015, we hosted our third consecutive R&D Day in New York City. Alnylam management and key opinion leaders discussed our most advanced clinical programs, reviewing all the latest data and providing guidance on development plans for the ATTR amyloidosis programs, fitusiran (ALN-AT3), ALN-CC5, ALN-AS1, and ALN-PCSsc.




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Positive Data with Monthly Dosing Cohorts from Ongoing Phase 1 Trial with Fitusiran (ALN-AT3) for the Treatment of Hemophilia and Rare Bleeding Disorders

December 7, 2015

Positive Data with Monthly Dosing Cohorts from Ongoing Phase 1 Trial with Fitusiran (ALN-AT3) for the Treatment of Hemophilia and Rare Bleeding Disorders

We reported new data from our Phase 1 study with the newly named fitusiran (ALN-AT3), an investigational RNAi therapeutic targeting antithrombin (AT) for the treatment of hemophilia and rare bleeding disorders. Interim results – presented at the American Society of Hematology (ASH) 2015 Annual Meeting, held December 5 – 8, 2015 – showed that monthly, subcutaneous administration of fitusiran achieved potent and dose-dependent lowering of AT of up to 88% in patients with hemophilia. This AT lowering was associated with statistically significant increases in thrombin generation and an 85% reduction in estimated median annualized bleeding rates (ABR) in all evaluable cohorts. The observed bleeding rates are comparable to those reported for prophylactic intravenous infusions of replacement factors in patients with hemophilia. Fitusiran was found to be generally well tolerated to date, including no thromboembolic events or clinically significant increases in D-dimer, a biomarker of excessive clot formation.



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Positive Interim Results from Phase 1/2 Clinical Study with ALN-CC5 for the Treatment of Complement-Mediated Diseases

December 6, 2015

Positive Interim Results from Phase 1/2 Clinical Study with ALN-CC5 for the Treatment of Complement-Mediated Diseases

We reported new data from our ongoing Phase 1/2 clinical study with ALN-CC5, an investigational RNAi therapeutic targeting complement component C5 for the treatment of complement-mediated diseases. Data were presented at the American Society of Hematology (ASH) 2015 Annual Meeting, held December 5 – 8, 2015.  Results showed that administration of ALN-CC5 achieved up to 99% knockdown of serum C5 and up to 98% inhibition of serum hemolytic activity, an assay for complement activity.  Further, ALN-CC5 administration resulted in low levels of residual C5, which – based on comparisons from separate studies – were at or below the estimated levels of free C5 observed at therapeutic doses of eculizumab, an approved anti-C5 monoclonal antibody. The effects were also found to be highly durable, with C5 knockdown and complement inhibition results supporting a once monthly and possibly a once quarterly subcutaneous dose regimen.  Importantly, ALN-CC5 was shown to be generally well tolerated, with no clinically significant, drug-related adverse events to date.




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Pre-Clinical Results from ALN-HBV for the Treatment of Hepatitis B Virus Infection

November 15, 2015

Pre-Clinical Results from ALN-HBV for the Treatment of Hepatitis B Virus Infection

We presented new pre-clinical data with ALN-HBV, an investigational RNAi therapeutic targeting the Hepatitis B Virus (HBV) genome for the treatment of HBV infection. The ALN-HBV siRNA targets a highly conserved site across genotypes A-J, mapping to the X open reading frame, which is downstream from the most prevalent integration hotspot targeted by siRNAs from other developers. ALN-HBV is thus expected to achieve potent knockdown of HBV surface antigen (HBsAg) expressed by both covalently closed circular DNA (cccDNA) and integrated HBV DNA. Pre-clinical study results in rodent HBV models showed that subcutaneous administration of ALN-HBV led to potent and durable knockdown of HBsAg. Single doses of ALN-HBV in mice resulted in an up to 3.6 log10 and a mean of 1.6 log10 reduction of HBsAg 15 days after a single dose. Further, multiple doses of ALN-HBV in rats showed highly durable knockdown, with effects lasting up to 4 months following three weekly doses of ALN-HBV at 3 mg/kg. In addition, ALN-HBV was generally well tolerated in all rodent models.


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