Inclisiran for high cholesterol
The results of a phase 2 dose-finding study (ORION-1) were recently published in the NEJM by Kausik et al.
About ten years ago it was discovered that the protein PCSK9 regulates liver receptors that clear LDL cholesterol by causing them to be destroyed and recycled. Therefore, binding or reducing PCKS9 allows liver LDL receptors to persist for longer and clear more cholesterol.
The new monoclonal antibodies evolocumab and alirocumab act by binding to PCSK9. Inclisiran targets production of the protein PCSK9 via a mechanism called RNA interference and silencing, resulting in decreased PCKS9.
A single subcutaneous dose appears to reduce cholesterol by around 35-40% which persists for at least 8 months. Further long term studies are still needed on bigger patient groups to determine the effect on cardiovascular outcomes, but inclisiran looks to be an interesting proposition with the convenience of annual or bi-annual dosing.