02 Jul, 2013 New Pre-Clinical Data with ALN-AT3
We presented new pre-clinical with ALN-AT3, an RNAi therapeutic targeting antithrombin (AT) for the treatment of hemophilia and rare bleeding disorders (RBD) at the XXIV Congress of the International Society of Thrombosis and Haemostasis (ISTH) being held June 29 – July 4. These data demonstrate that ALN-AT3 can normalize thrombin generation and improve hemostasis in hemophilia mice and fully correct thrombin generation in a non-human primate (NHP) hemophilia “inhibitor” model.
In a microvessel laser injury model, hemophilia mice treated with a single subcutaneous dose of ALN-AT3 showed improvements in hemostatic plug formation compared to untreated hemophilia mice. In wild type NHPs, repeat dosing with ALN-AT3 resulted in potent, titratable, and reversible silencing of plasma AT3. In an NHP hemophilia “inhibitor” model, in which a Hemophilia A phenotype was induced via administration of a polyclonal anti-factor VIII antibody, ALN-AT3-treated animals showed dose-dependent increases in thrombin generation, fully restoring this hemostatic parameter back to normal levels. Lastly, highly exaggerated doses of ALN-AT3 that result in essentially complete ablation of AT were very well tolerated in hemophilia mice. These results support a greater than 100-fold therapeutic index for ALN-AT3 in the hemophilia setting.
We plan to review these data, as well as progress from other Alnylam 5×15 programs, at our upcoming R&D Day on July 11, 2013 in New York City.