VERVE-102 is an investigational in vivo base-editing gene therapy developed by Verve Therapeutics (with Eli Lilly involved via acquisition/collaboration) that aims to provide a one-time treatment for high cholesterol by permanently inactivating the PCSK9 gene in the liver.

Key Mechanism

• It delivers an adenine base editor (ABE) mRNA and a guide RNA (gRNA) targeting PCSK9 via a GalNAc-conjugated lipid nanoparticle (LNP).
• The base editor makes a precise A-to-G change, introducing a premature stop codon that turns off PCSK9 production without double-strand DNA breaks (unlike traditional CRISPR-Cas9).
• This reduces circulating PCSK9 protein, which normally degrades LDL receptors, leading to increased LDL clearance from the blood.
• Administered as a single intravenous infusion over ~2–4 hours.37

Latest Clinical Data (Heart-2 Phase 1b Trial)

• Presented: May 25, 2026, as a late-breaking oral at the European Atherosclerosis Society (EAS) Congress; simultaneously published in The New England Journal of Medicine.
• Patients: Interim analysis of 35 adults with heterozygous familial hypercholesterolemia (HeFH) or premature coronary artery disease (CAD) — high-risk group needing additional LDL-C lowering despite standard therapies.
• Dosing: Single-ascending doses from 0.3 mg/kg to 1.0 mg/kg total RNA.
• Efficacy (dose-dependent, time-averaged from Day 28 onward):
  • PCSK9 reductions: 51% (lowest dose) to 88% (highest 1.0 mg/kg dose).
  • LDL-C reductions: 9% (0.3 mg/kg) up to 62% (1.0 mg/kg), with an absolute drop of ~78 mg/dL at the highest dose.
  • Effects were sustained up to 18 months (longest follow-up in the data cut).
• Earlier interim data (April 2025, first 14 patients) showed up to 69% max LDL-C reduction at 0.6 mg/kg.26

Safety

• Generally well-tolerated with no treatment-related serious adverse events in the reported data.
• No clinically significant laboratory abnormalities (e.g., no major liver toxicity signals like those seen in the earlier VERVE-101 program).
• Mild infusion-related reactions possible (one Grade 2 case resolved with acetaminophen).
• One unrelated aspiration pneumonitis noted.28

Development Status and Next Steps

• Lilly plans to begin Phase 2 enrollment by the end of 2026.
• Targets initially HeFH, with potential expansion to broader atherosclerotic cardiovascular disease (ASCVD) populations.
• This follows Lilly’s involvement with Verve (acquisition/rights expansion), positioning it as a potential “one-and-done” alternative to daily statins, monthly PCSK9 injections (e.g., evolocumab), or twice-yearly inclisiran.0

Context and Caveats

This represents exciting early proof-of-concept for in vivo base editing in humans for cardiovascular disease. The durable effect could transform adherence issues in chronic lipid management. However:

• Phase 1b is small and open-label (no placebo control yet).
• Longer-term safety (e.g., off-target editing, immune responses, durability beyond 18 months) needs confirmation in larger trials.
• Accessibility, cost, and eligibility (e.g., liver function requirements) will be key future questions.

The NEJM publication or Lilly/Verve press releases from May 25, 2026. This could indeed mark a shift toward one-time genetic interventions for common conditions like hypercholesterolemia.