Alnylam and The Medicines Company reported positive initial results from the ongoing Phase 1 clinical trial with ALN-PCSsc, an investigational RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia.  Subcutaneous administration of ALN-PCSsc resulted in an up to 83% lowering of LDL-C, with an up to 64 ± 5% mean maximum reduction, comparable to published results for anti-PCSK9 monoclonal antibodies (Zhang XL., et al., BMC Med, 2015).  Similar reductions in LDL-C were seen in patients on and off concomitant statin therapy.  The effects of ALN-PCSsc were highly durable, with clinically significant and clamped reductions in LDL-C maintained for over 140 days, supportive of a once-quarterly and possibly bi-annual subcutaneous dose regimen. Maximal lowering effects on LDL-C were consistently achieved at a dose of 300 mg associated with a low injection volume of 1.5 mL. Importantly, ALN-PCSsc was generally well tolerated with no clinically significant adverse events to date. [spotlight-link icon="release" href="" type=" "]Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="" type="(0.4 MB PDF)"]View the poster[/spotlight-link] [spotlight-link icon="presentation" href="" type="(1.7 MB PDF)"]View the presentation[/spotlight-link]

We presented positive interim clinical data from our ongoing Phase 1 study for ALN-AT3, a subcutaneously administered, investigational RNAi therapeutic targeting antithrombin (AT) for the treatment of hemophilia and rare bleeding disorders. Data were presented at the International Society on Thrombosis and Haemostasis (ISTH) 2015 Congress held June 20 – 25, 2015. New clinical results from 12 subjects with severe hemophilia show that subcutaneous administration of ALN-AT3 achieved potent and dose-dependent knockdown of AT of up to 86%. AT knockdown was highly durable, with effects lasting over two months after the last dose, supporting further evaluation of a once-monthly subcutaneous dose regimen. In addition, AT knockdown was associated with statistically significant increases in thrombin generation with a mean increase of up to 350% and marked improvements in whole blood clotting; these results demonstrate a re-balancing of hemostasis in severe hemophilia subjects. Furthermore, in an exploratory post-hoc analysis, a reduced frequency of bleeding was observed at higher AT knockdown levels with a maximum bleed-free interval of 114 days. Very importantly, ALN-AT3 continues to be generally well tolerated. [spotlight-link icon="release" href="" type=" "]Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="" type="(614 KB PDF)"]View our Phase 1 data presentation[/spotlight-link]

We reported positive initial clinical results from our Phase 1/2 trial of ALN-CC5, an investigational RNAi therapeutic targeting complement component C5 for the treatment of complement-mediated diseases. The new clinical data are being presented at the 20th Congress of the European Hematology Association (EHA) held June 11 – 14, 2015. Initial study results from 12 healthy volunteer subjects showed that subcutaneous administration of a single dose of ALN-CC5 resulted in potent, dose-dependent, durable, and statistically significant knockdown of serum C5 of up to 96%. In addition, single dose administration of ALN-CC5 achieved inhibition of serum complement activity of up to 92%, including an up to 61% inhibition of serum hemolytic activity. Further, ALN-CC5 has been found to be generally well tolerated to date. [spotlight-link icon="release" href="" type=" "] Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="" type="(677 KB PDF)"] View our presentation[/spotlight-link]

We presented pre-clinical data on ALN-AAT, an investigational RNAi therapeutic targeting alpha-1 antitrypsin (AAT) for the treatment of AAT deficiency-associated liver disease. New data, presented at the Digestive Disease Week (DDW) meeting, held May 16 – 19, 2015, showed a robust knockdown of serum AAT of up to 93% in non-human primates (NHPs) with monthly subcutaneous dosing. This level of knockdown was highly durable, lasting for greater than 30 days following the final dose. Further, ALN-AAT was found to have a wide therapeutic index based on results from GLP toxicology studies. In addition, study results were reported from a transgenic mouse model of alpha-1 liver disease, where mice overexpress the human Z-AAT protein. [spotlight-link icon="release" href="" type=" "] Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="" type="(7 MB PDF)"] View the presentation [/spotlight-link]

We presented initial 12-month clinical data from our ongoing Phase 2 open-label extension (OLE) study with patisiran, an investigational RNAi therapeutic in development for the treatment of transthyretin (TTR)-mediated amyloidosis in patients with familial amyloidotic polyneuropathy (FAP). Study results, presented at the 67th Annual Meeting of the American Academy of Neurology (AAN) being held April 18 – 25, showed a mean 2.5 point decrease in modified Neuropathy Impairment Score (mNIS+7) at 12 months in patients who had reached the 12-month endpoint (N=20) 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. [spotlight-link icon="release" href="" type=" "] Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="" type="(497 KB PDF)"] View our presentation[/spotlight-link]


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