Design and baseline data of AZURE-HeFH, a phase 3 study assessing the effect of the oral PCSK9 inhibitor laroprovstat on LDL cholesterol in patients with heterozygous familial hypercholesterolaemia
E S Stroes, R S Rosenson, R Santos, F Raal, L Tokgozoglu, U Mattsson, E Wijkmark, P Johanson, N Pagidipati, R Al-Lamee, E Cenko, J Nordanstig, M Szarek, M P Bonaca, G G SchwartzAbstract
Background/Introduction
Patients with heterozygous familial hypercholesterolaemia (HeFH), if untreated or undertreated, are characterised by lifelong exposure to elevated low density lipoprotein cholesterol (LDLc) levels, associated with a markedly increased risk of atherosclerotic cardiovascular disease (ASCVD). Recent surveys, however, show that less than one quarter of HeFH patients achieve guideline-directed LDLc goals with conventional oral lipid-lowering therapy (LLT). The use of injectable PCSK9 inhibitors has been limited due to access, cost and acceptability. Laroprovstat (LARO) is a novel, oral PCSK9 inhibitor that was well-tolerated and produced large LDLc reductions in a Phase 2 trial when added to a statin without food interactions.
Purpose
To present design and preliminary baseline data for the evaluation of efficacy and safety of LARO vs placebo added to background oral LLT for reducing LDLc in patients with HeFH.
Methods
AZURE-HeFH is a fully enrolled, Phase 3, randomised, double-blind, placebo-controlled trial in participants ≥18 years with HeFH confirmed by genetic testing or definite clinical diagnosis, with either a prior ASCVD event and LDLc ≥1.4 mmol/L or no prior ASCVD event and LDLc ≥1.8 mmol/L; all on maximally tolerated oral LLT (Figure). The primary outcome is the relative change from baseline in LDLc at 12 weeks. Participants are being followed for one year with secondary endpoints including relative change from baseline in LDLc at 52 weeks.
Results
Based on preliminary data, 472 participants were randomised and dosed between June and December 2025. Baseline characteristics are shown in the Table. Approximately 21% had a prior ASCVD event. More than 94% received background statin therapy with >80% using high-intensity statin therapy. Ezetimibe was used by 73.1% of participants. Mean baseline LDLc was 2.95 mmol/L. The trial is ongoing with final results anticipated in 2027.
Conclusion(s)
AZURE-HeFH has completed enrollment with 472 participants with HeFH randomised and received treatment with LARO or placebo, added to conventional oral LLT. Baseline characteristics demonstrate a multinational cohort of HeFH patients who did not achieve LDLc goals despite oral background therapies. The results of AZURE-HeFH will determine whether those goals may be achieved with oral medication including LARO as a safe, well-tolerated and highly effective PCSK9 inhibitor.