Verve’s 2nd swing at PCSK9 editing yields clean safety profile, teeing up Lilly opt-in decision

Title

"Verve Therapeutics Achieves Safety Breakthrough with VERVE-102, Setting Stage for Lilly's Opt-In Decision"

Keywords

• Verve Therapeutics
• PCSK9 gene editing
• VERVE-102
• LDL cholesterol reduction
• CRISPR base editing
• Eli Lilly
• Cardiovascular disease treatment
• Lipid nanoparticles
• Familial hypercholesterolemia
• Gene therapy

Key Facts

- VERVE-102 Overview:
VERVE-102 is an in vivo CRISPR base-editing therapy that targets and permanently inactivates the PCSK9 gene in liver cells, aiming to reduce LDL (low-density lipoprotein) cholesterol levels in patients with heterozygous familial hypercholesterolemia or premature coronary artery disease134.

- Improvement Over Predecessor (VERVE-101):
Verve pivoted from VERVE-101, which showed safety concerns due to its lipid nanoparticle (LNP) delivery system. VERVE-102 uses an improved GalNAc-LNP delivery platform, significantly enhancing its safety profile while maintaining efficacy134.

- Clinical Trial Results: In the phase 1b trial (Heart-2), VERVE-102 demonstrated:

• Dose-dependent reductions in LDL cholesterol (up to 69% in high-dose patients).
• No clinically significant changes in bilirubin, platelets, or two liver enzymes.
• No serious adverse events or dose-limiting toxicities147.

- Efficacy:
VERVE-102 achieved a mean LDL-C reduction of 53% across doses, with maximum reductions observed in the highest dose cohort4. Its one-time treatment design provides a durable cholesterol-lowering effect, potentially differentiating it from existing biannual siRNA treatments like Novartis’s Leqvio47.

- Lilly's Opt-In Decision:
Eli Lilly holds the option to co-develop and commercialize VERVE-102 as part of a collaboration signed in 2023. Lilly's decision, expected in late 2025, could lead to shared development costs and a 50/50 profit split for U.S. commercialization14.

- Competition Landscape:
VERVE-102 competes in the PCSK9 inhibitor market against established monoclonal antibodies (Amgen's Repatha, Sanofi/Regeneron's Praluent), siRNA treatments, and investigational oral PCSK9 inhibitors (AstraZeneca, Merck). Its potential for a long-lasting one-dose treatment could offer a paradigm shift in cardiovascular care17.

- Next Steps:
Verve plans to commence a phase 2 trial for VERVE-102 in the second half of 2025, expanding to U.S. sites after receiving FDA clearance14.

Conclusion

VERVE-102's promising safety and efficacy results position it as a groundbreaking solution in cardiovascular disease management. It not only strengthens Verve Therapeutics’ pipeline but also sets the stage for Eli Lilly’s pivotal opt-in decision, marking a potential turning point in the fight against hypercholesterolemia.

Sources:

1. https://www.fiercebiotech.com/biotech/verves-second-swing-pcsk9-editing-yields-clean-safety-profile-teeing-lilly-opt-decision

3. https://www.tctmd.com/news/topline-data-point-promise-verve-102-gene-editing-therapy

4. https://www.globenewswire.com/news-release/2025/04/14/3060774/0/en/Verve-Therapeutics-Announces-Positive-Initial-Data-from-the-Heart-2-Phase-1b-Clinical-Trial-of-VERVE-102-an-In-Vivo-Base-Editing-Medicine-Targeting-PCSK9.html

7. https://www.biospace.com/drug-development/verves-base-editor-numerically-beats-other-cholesterol-lowering-drugs