- Phase 1b Heart‑2 (n=35) single IV VERVE‑102 doses 0.3–1.0 mg/kg yielded dose‑dependent PCSK9 reductions of 51–88% and LDL‑C reductions up to 62% (1.0 mg/kg), durable to 18 months.
- VERVE‑102 is an in vivo adenine base editor delivered as mRNA plus guide RNA in a GalNAc‑LNP to inactivate hepatic PCSK9.
- No treatment‑related serious adverse events or dose‑limiting toxicities were reported; adverse events were limited to low‑grade infusion reactions and fatigue.
- FDA granted Fast Track for LDL‑C reduction; Lilly plans to start Phase 2 enrollment by year‑end and participants are expected to enter up to 15 years of follow‑up.
Study results
In the Phase 1b Heart‑2 interim analysis (n=35), single IV VERVE‑102 doses (0.3–1.0 mg/kg) produced dose‑dependent PCSK9 reductions of 51–88% and corresponding LDL‑C reductions ranging from 9% to 62% (highest at 1.0 mg/kg), with durability observed up to 18 months in a subset of participants.
Safety
VERVE‑102 was well tolerated across dose cohorts with no treatment‑related serious adverse events or dose‑limiting toxicities; adverse events were limited to low‑grade infusion‑related reactions and fatigue, all participants received full planned doses and no one withdrew.
Drug and trial design
VERVE‑102 is an in vivo adenine base editor delivered as mRNA plus guide RNA in a GalNAc‑LNP, administered as a single ~4‑hour IV infusion to inactivate hepatic PCSK9; Heart‑2 is an open‑label, single‑ascending dose Phase 1b in adults with heterozygous familial hypercholesterolemia or premature coronary artery disease who need additional LDL‑C lowering despite maximally tolerated oral therapy; cohorts spanned 0.3–1.0 mg/kg, median follow‑up was ~9 months as of Feb 27, 2026, and 15 participants had ≥1 year follow‑up, with planned long‑term follow‑up up to 15 years.
Regulatory and next steps
The FDA has granted Fast Track designation for LDL‑C reduction in high lifetime cardiovascular risk; Lilly plans to initiate Phase 2 enrollment by year‑end, and a separate Pulse‑1 Phase 1b study of VERVE‑201 (ANGPTL3 target) is ongoing.
