Key result
Single-dose VERVE-102 cuts LDL cholesterol by up to ~62% in a dose-dependent manner.
Why the study?
Does a single dose of VERVE-102 safely reduce blood PCSK9 protein and LDL cholesterol levels in participants with hypercholesterolemia?
Does a single dose of VERVE-102 safely reduce blood PCSK9 protein and LDL cholesterol levels in participants with hypercholesterolemia?
Answers are grounded in this paper and cite their sources.
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Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Results from two early studies published in NEJM could have important implications for patients with heart failure (HF) and reduced LVEF and for adults with heterozygous familial hypercholesterolemia (HFH) or premature coronary artery disease, respectively.”
A single dose of the in vivo base editor VERVE-102 safely produces substantial, dose-dependent, and durable reductions in PCSK9 and LDL cholesterol levels.
BACKGROUND: in the liver. The objectives were to assess safety and changes in blood PCSK9 protein and LDL cholesterol levels. RESULTS: A total of 35 participants across the six dose cohorts received VERVE-102 and had at least 28 days of follow-up. No dose-limiting toxic effects occurred. Mild-to-moderate infusion-related reactions and transient elevations in alanine aminotransferase levels were observed. Aspiration pneumonitis occurred in a participant with gastroesophageal reflux disease. Dose-dependent mean reductions in the PCSK9 level ranged from 51% at the 0.3-mg-per-kilogram dose to 88% at the 1.0-mg-per-kilogram dose. Corresponding reductions in the LDL cholesterol level ranged from 9% at the 0.3-mg-per-kilogram dose to 62% at the 1.0-mg-per-kilogram dose, with an absolute reduction of 78 mg per deciliter at the highest dose. Reductions appeared to be durable throughout follow-up, which was at least 1 year in 15 participants. CONCLUSIONS: One dose of VERVE-102 led to dose-dependent, substantial, and sustained reductions in PCSK9 and LDL cholesterol levels. (Funded by Verve Therapeutics; ClinicalTrials.gov number, NCT06164730.).
Journal, society, and media accounts. Useful signal, not independent expert judgment.
Vafai et al. (2026) studied Hypercholesterolemia (n=35). VERVE-102 was evaluated on safety and changes in blood PCSK9 protein and LDL cholesterol levels. One dose of VERVE-102 led to dose-dependent reductions in PCSK9 (up to 88%) and LDL cholesterol (up to 62%, absolute reduction 78 mg/dL) at the 1.0-mg/kg dose.
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