NEJM publishes Heart-2 Phase 1 results: VERVE-102 lowered LDL by 62% on average at the top dose, lasting at least a year

Eli Lilly/VERVE-102 (PCSK9 base editor)

NEJM published the Heart-2 Phase 1 trial of VERVE-102, a one-time intravenous infusion that base-edits the PCSK9 gene in the liver to lower cholesterol, in 35 adults with inherited high cholesterol or early heart disease. At the 1.0 mg/kg top dose, PCSK9 protein fell 88 percent and LDL cholesterol 62 percent, with reductions sustained for up to 18 months; side effects were mostly mild infusion reactions and fatigue with no serious adverse events.

• Phase 1b Heart-2 trial in 35 adults with inherited high cholesterol or early heart disease
• Top dose (1.0 mg/kg): PCSK9 reduced 88%, LDL-C reduced 62%; effects sustained up to 18 months
• Dose-dependent results: PCSK9 reductions ranged 51–88%, LDL-C reductions 9–62% across doses
• No treatment-related serious adverse events, no dose-limiting toxicities; side effects mostly mild infusion reactions