A single infusion of a CRISPR-based gene editing therapy significantly reduced LDL-C and PCSK9 levels in patients with heterozygous familial hypercholesterolemia (HeFH), based on findings from the VERVE-101 trial presented Nov. 12 at AHA 2023. In presenting the findings, Andrew Bellinger, MD, PhD, said they provide the first proof-of-concept for in vivo DNA base editing in humans.

The ongoing, first-in-human study enrolled 10 patients (8 men/2 women, mean age 54 years) from the UK or New Zealand, all of whom had HeFH and an average LDL-C of 201 mg/dL. Most study participants had pre-existing severe coronary artery disease and had undergone prior coronary revascularization. Roughly half of participants had experienced at least one myocardial infarction. Nearly all were on statin therapy, and none were taking PCSK9 inhibitors while enrolled in the study.

All patients received a single intravenous infusion of VERVE-101, with the first cohort (n=3) receiving a low dose of 0.1 mg/kg and other cohorts receiving escalating doses, after consultation with an independent safety monitoring board. The highest dose received was 0.6 mg/kg.

Overall findings showed that three patients receiving the highest two VERVE-101 doses (0.45 mg/kg and 0.6 mg) saw the greatest reductions in LDL-C and PCSK9 protein levels. The two patients in the 0.45 mg/kg group saw reductions in LDL-C by 39% and 48%, respectively, and in PCSK9 by 47% and 59%. The one patient in the 0.6 group experienced a reduction in LDL-C of 55% and in PCSK9 of 84%. Bellinger noted that the LDL change has been durable up to six months so far, with follow-up ongoing.

“Instead of daily pills or intermittent injections over decades to lower bad cholesterol, this study reveals the potential for a new treatment option – a single-course therapy that may lead to deep LDL-C lowering for decades,” Bellinger said.