ALN-TTR02: Interim Phase II data

Interim data from 19 evaluable patients with TTR-mediated amyloidosis in an open-label, dose-escalation, international Phase II trial showed that multiple doses of IV ALN-TTR02 led to rapid, dose-dependent and significant knockdown of serum TTR protein levels of up to 92.8%. Specifically, maximum percent reductions in TTR were 37.8% following the first dose of 0.01 mg/kg ALN-TTR02 every 4 weeks and 34.4% following the second dose; 58% following the first dose of 0.05 mg/kg ALN-TTR02 every 4 weeks and 58.5% following the second dose; 81.7% following the first dose of 0.15 mg/kg ALN-TTR02 every 4 weeks and 86% following the second dose; 87.5% following the first dose of 0.3 mg/kg ALN-TTR02 every 4 weeks and 90.8% following the second dose; and 83.8% following the first dose of 0.3 mg/kg ALN-TTR02 every 3 weeks and 92.8% following the second dose.

Additionally, mean percent reductions in TTR at nadir - the point at which serum TTR levels were the lowest for each dosing period - were 20.1% following the first dose of 0.01 mg/kg ALN-TTR02 every 4 weeks and 32.9% following the second dose; 48.4% following the first dose of 0.05 mg/kg ALN-TTR02 every 4 weeks and 46.9% following the second dose; 74.5% following the first dose of 0.15 mg/kg ALN-TTR02 every 4 weeks (p<0.001 compared to the 0.01 mg/kg dose) and 77% following the second dose (p<0.01 compared to the 0.01 mg/kg dose); 82.6% following the first dose of 0.3 mg/kg ALN-TTR02 every 4 weeks (p<0.001 compared to the 0.01 mg/kg dose) and 84.8% following the second dose (p<0.001 compared to the 0.01 mg/kg dose); and 83.1% following the first dose of 0.3 mg/kg ALN-TTR02 every 3 weeks (p<0.001 compared to the 0.01 mg/kg dose) and 87.4% following the second dose (p<0.001 compared to the 0.01 mg/kg dose). Similar knockdown was observed in patients with both wild-type and mutant TTR protein levels. ...