In this article, the authors report interim results of Heart 2, a phase 1, open label, single ascending dose study of VERVE 102, a GalNAc lipid nanoparticle delivering mRNA for an adenine base editor and guide RNA targeting a proprotein convertase subtilisin–kexin type 9 (PCSK9) intron 1 splice site. Thirty-five adults with heterozygous familial hypercholesterolemia or premature coronary artery disease received 0.3 to 1.0 mg/kg intravenously. The median follow–up was approximately nine months, with 15 patients followed for at least one year. No dose–limiting toxicity, deaths, or withdrawals occurred. Infusion reactions were grade 1 to 2, and alanine aminotransferase (ALT) elevations were transient. At 1.0 mg/kg, PCSK9 and low-density lipoprotein (LDL) cholesterol fell by 88 percent and 62 percent, respectively, corresponding to a 78 mg/dL LDL reduction.
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In Vivo Base Editing of PCSK9 With VERVE-102 for Hypercholesterolemia
Submitted by: Vincent Sier
Source: The New England Journal of Medicine
Author(s): Scott B. Vafai, Jörg Täubel, Thomas Ashdown, Riyaz S. Patel, Sadaf Diamondali, Jaimini Cegla, Handrean Soran, Bilal Bashir, Alexander Abitbol, Daniel Gaudet, Alex Lauzière, Liam R. Brunham, David E. Newby, Stephen J. Nicholls, Russell S. Scott, Jane Kerr, Jean-Claude Tardif, Catherine Lunken, Steve E. Humphries, Verena Karsten, Patrick D. Tyler, Xinyan Zhang, Nidal Huniti, Patrick A. Flight, Chelsey L. Jensen, Rick Falzone, Joseph C. Biedenkapp, Troy Lister, Leslie E. Stolz, Amit V. Khera, Sekar Kathiresan
