08 Dec, 2014 Positive Initial Phase 1 Clinical Results for ALN-AT3, in Development for the Treatment of Hemophilia and Rare Bleeding Disorders
We presented positive initial Phase 1 data for ALN-AT3, an investigational RNAi therapeutic targeting antithrombin (AT) for the treatment of hemophilia and rare bleeding disorders. Preliminary results, presented at the 56th Annual Meeting of the American Society of Hematology (ASH), showed that subcutaneous administration of ALN-AT3 given once weekly for three weeks at low doses of 15 (N=3) or 45 (N=1) micrograms/kg (mcg/kg) resulted in an up to 57% knockdown of AT in hemophilia subjects. The effects of ALN-AT3 lasted for about 60 days after a single dose. ALN-AT3 was found to be well tolerated in both healthy volunteers and hemophilia subjects enrolled in the study. These initial results show preliminary evidence for potency and durability of RNAi therapeutics at mcg/kg subcutaneous doses in human studies, and are the first clinical data to be reported for Alnylam’s Enhanced Stabilization Chemistry (ESC)-GalNAc conjugate technology.
The unmet need for new therapeutic options to treat hemophilia patients remains very high. We believe these current data are very encouraging and point to the significant potential for ALN-AT3 as an innovative approach for the treatment of hemophilia and rare bleeding disorders.
In addition to the Phase 1 clinical data, we presented new pre-clinical data with ALN-AT3 in a symposium at ASH. In a study conducted in non-human primates, monthly subcutaneous dosing of ALN-AT3 was found to result in robust, durable, and dose-dependent knockdown of AT. These data, combined with the emerging human durability data, may support monthly dosing of ALN-AT3 in hemophilia subjects. In addition, new results from a chronic toxicity study performed in hemophilia A mice showed that weekly dosing of ALN-AT3 confers a statistically significant survival benefit as compared with animals receiving placebo. Hemophilia A mice are prone to premature death due to their bleeding diathesis, and these results suggest that ALN-AT3 may be able to achieve a disease modifying effect by rebalancing the coagulation cascade through AT knockdown.