Lilly’s VERVE-102 Single Dose Cuts PCSK9 Up to 88% and LDL-C 62%
LLY•Eli Lilly’s investigational base editor VERVE-102 achieved dose-dependent reductions in PCSK9 of 51–88% and LDL-C of 9–62% across six dose cohorts in 35 high-risk adults, with effects sustained up to 18 months. Lilly plans to begin a Phase 2 study by year-end after observing no serious adverse events.
1. Phase 1b Heart-2 Trial Results
In the open-label, single-ascending dose Heart-2 study involving 35 participants with heterozygous familial hypercholesterolemia or premature CAD, a single intravenous infusion of VERVE-102 produced mean PCSK9 reductions ranging from 51% at 0.3 mg/kg to 88% at 1.0 mg/kg, alongside LDL-C decreases of 9% to 62% across six dose cohorts.
2. Durability of Lipid Lowering
Participants exhibited sustained PCSK9 and LDL-C reductions for up to 18 months post-infusion, with a median follow-up of nine months and 15 subjects followed for at least one year, indicating durable gene editing effects from a single administration.
3. Safety and Tolerability
VERVE-102 was well tolerated at all dose levels with no treatment-related serious adverse events or dose-limiting toxicities; reported adverse events were low-grade infusion reactions and transient fatigue, and no participants withdrew from the study.
4. Planned Phase 2 Study
Building on the favorable safety and durable efficacy data, Lilly intends to initiate a Phase 2 clinical trial of VERVE-102 for hypercholesterolemia by the end of this year, leveraging its GalNAc-LNP delivery platform to further evaluate dosing, efficacy and long-term outcomes.
