Clinical read Europe is about to approve a CETP inhibitor on the endpoint this class has always won, and before the endpoint it has always lost. Four serious attempts preceded obicetrapib. Pfizer’s torcetrapib was terminated in 2006 when ILLUMINATE showed excess mortality from off-target effects. Roche’s dalcetrapib stopped for futility in 2012. Lilly’s evacetrapib stopped for futility in 2015 despite substantial lipid changes. Merck’s anacetrapib produced a modest benefit in REVEAL and was never filed. Not one of those failures was a failure to move lipids. Every one of them moved lipids convincingly and then failed to convert that into fewer cardiovascular events, or actively harmed patients. So a positive opinion built on BROADWAY, BROOKLYN and TANDEM, all LDL-lowering studies, clears exactly the bar the class has cleared four times before. The bar it has never cleared is the one still open: PREVAIL, a cardiovascular outcomes trial that randomised more than 9,500 patients and completed enrolment in April 2024. Two things genuinely look different this time, a placebo-like tolerability profile suggesting the off-target problem that killed torcetrapib may be solved, and a low-dose oral design. Neither is evidence of outcome benefit. Read the royalty structure as the market’s own hedge: Menarini takes the commercial risk in Europe while NewAmsterdam keeps mid-twenties royalties at the top tier, which is an unusually strong split for an ex-US licence and suggests it was negotiated from a position of confidence. PREVAIL will decide whether that confidence was warranted.