Positive Top-Line Data from Phase 1 Clinical Trial with ALN-AT3 for Treatment of Hemophilia and Rare Bleeding Disorders

We presented positive top-line data from our Phase 1 clinical trial with ALN-AT3, an RNAi therapeutic targeting antithrombin (AT) in development for the treatment of hemophilia and rare bleeding disorders (RBD). In “Part A” of the Phase 1 study, we gave a single dose of drug to healthy volunteers to evaluate the drug’s safety and tolerability. Importantly, we had a dose escalation stopping rule at a maximum of 40% AT knockdown. Initial results, presented at the World Federation of Hemophilia (WFH) 2014 World Congress held May 11 – 15, 2014 in Melbourne, Australia, show that a single, low subcutaneous dose of ALN-AT3 at 0.03 mg/kg resulted in an up to 28-32% knockdown of AT at nadir relative to placebo (p <0.01 by ANOVA) and a temporally associated increase in peak thrombin generation (p <0.01). ALN-AT3 was found to be well tolerated with no significant adverse events reported.  With these results in hand, we have now proceeded to “Part B” of the Phase 1 study.

These human study results are the first to be reported for Alnylam’s Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate technology, which enables subcutaneous dosing with increased potency and durability, and a wide therapeutic index.  Further, the achievement of target knockdown at such a low dose of 0.03 mg/kg is unprecedented. These initial clinical results demonstrate a greater than 50-fold potency improvement with ESC-GalNAc conjugates relative to standard template chemistry conjugates.

These clinical findings, combined with our earlier pre-clinical results, support our belief that ALN-AT3 could be an attractive new prophylactic option for people with hemophilia, including those with inhibitors.