We have published complete study results from our Phase I trial with ALN-PCS in The Lancet. As reported in the paper, ALN-PCS administration resulted in a rapid, dose-dependent reduction in plasma PCSK9 of up to 84% relative to baseline and placebo, with a corresponding reduction in serum levels of low-density lipoprotein cholesterol (LDL-C) – or “bad” cholesterol – of up to 57% relative to baseline and placebo. The knockdown of PCSK9 and lowering of LDL-C were also found to be durable, with effects lasting for weeks after a single dose. In addition, ALN-PCS was shown to be generally safe and well tolerated in this Phase I study and there were no serious adverse events related to study drug administration. This new paper documents the first human proof of concept for an RNAi therapeutic impacting a clinically validated endpoint, namely LDL-C.
We believe that the unique mechanism of action for ALN-PCS, which inhibits the synthesis of PCSK9 inside liver cells – thereby reducing both its intracellular and extracellular functions – provides a differentiated strategy for PCSK9 antagonism. These Phase I data, as reported in The Lancet, demonstrate that inhibition of PCSK9 synthesis by an RNAi therapeutic may be a potentially safe and novel approach to reduce LDL-C.