PCSK9 base editing (VERVE-102)
Metabolic Health · In-vivo base editing
Tier C-
High-risk evidence profile
Bottom line
Read Off Label grades PCSK9 base editing (VERVE-102) as C- (4.0/10) based on weak evidence, high benefit magnitude, and a med-high-risk safety profile.
Its high-risk evidence profile reflects a Safety score of 3.5/10; reported benefits and harms can differ by indication, dose, route, duration, and population.
Verve Therapeutics (Lilly).
Studied, labeled, or reported-use context: Single IV infusion (0. — Investigational; not individualized guidance.
What the evidence says
Verve Therapeutics (Lilly). Heart-2 Phase 1b (NEJM 2026, n=35): a single infusion reduced PCSK9 up to 88% and LDL-C up to 62% (max -69%), durable to 18 months, no serious adverse events. First-in-human in-vivo base editing for hypercholesterolemia; Phase 2 planned late 2026. Frontier modality, durability/safety still early. Industry-sponsored.
Mechanism
One-time in-vivo CRISPR base edit of the PCSK9 gene in hepatocytes (lipid-nanoparticle delivered), permanently lowering PCSK9 and LDL-C, a single-dose alternative to chronic PCSK9 therapy.
Studied, labeled, or reported dose & route
Single IV infusion (0.3-1.0 mg/kg in Phase 1b)
This records doses and routes described in studies, approved labeling, clinical practice, or documented use. It is not individualized guidance and does not establish safety; context changes with indication, formulation, health history, monitoring, and other medicines.
Citations
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Common questions
- What does the evidence show about PCSK9 base editing (VERVE-102)'s effects?
- Read Off Label rates the evidence for PCSK9 base editing (VERVE-102) as Weak and the benefit magnitude as high, producing an overall grade of C- (4.0/10). Verve Therapeutics (Lilly).
- What safety findings are reported for PCSK9 base editing (VERVE-102)?
- PCSK9 base editing (VERVE-102) has a med-high risk profile in the database. Med-High (first-in-human gene editing; long-term off-target and durability unknown) Legal status: Investigational (Phase 1b/2; not approved).
- What does the low Safety score for PCSK9 base editing (VERVE-102) represent?
- The Safety score is 3.5/10. It records the substantial harms described for one or more use contexts; the Benefit score, indication, dose, route, duration, population, and legal status remain separate parts of the evidence profile.
- What doses or routes are reported for PCSK9 base editing (VERVE-102)?
- Single IV infusion (0.3-1.0 mg/kg in Phase 1b) This is context from studies, approved labeling, clinical practice, or documented use; it is not individualized guidance and does not establish safety.
- How does PCSK9 base editing (VERVE-102) work?
- One-time in-vivo CRISPR base edit of the PCSK9 gene in hepatocytes (lipid-nanoparticle delivered), permanently lowering PCSK9 and LDL-C, a single-dose alternative to chronic PCSK9 therapy.
This is an independent synthesis of published research by a non-clinician. Scores are opinions supported by citations, not prescriptions. See the full disclaimer and methodology for how this score was produced and what it does and doesn't mean.