Topcoin,

The issue of biomarkers in clinical trials affecting the blinding is not new. For example, CETP inhibitors elicit a huge increase in HDL-C. PCSK9 drugs (Repatha, Praluent, Inclisiran) dramatically lower LDL-C. Bempedoic acid lowers LDL-C and hsCRP. Canakinumab lowers hsCRP. Vascepa lowers plasma triglycerides. SGLT2 inhibitors, GLP-1R agonists, and DPP4 inhibitors lower glucose. All of these completed or ongoing cardiovascular outcomes trials for the aforementioned drugs are subject to the same concern of biomarker modulation affecting true blinding when they are tested in clinical trials. The most common path to drug approval is first clinical validation for modulation of biomarker (HDL-C, LDL-C, triglycerides, glucose, hsCRP) and then after that has been firmly established to do a cardiovascular outcomes trial. So it is almost unavoidable to have this issue of biomarker potentially confounding the blinding. How do regulators deal with this now and in the future? Great question. But I don't know the answer!

BearDownAZ