Key Takeaways
Eli Lilly’s investigational base editor, VERVE-102, reduced “bad” cholesterol by up to 62% with a single dose in a clinical trial, a result that could challenge the multi-billion dollar market for chronic cholesterol treatments.
"These early data give us encouraging evidence that in vivo base editing of PCSK9 may offer a novel approach to achieving substantial and durable LDL-C reduction with a one-time treatment," said Riyaz S. Patel, a cardiologist at Barts Health NHS Trust and professor at University College London.
The positive results come from the Phase 1b Heart-2 study of 35 participants with genetic high cholesterol or premature coronary artery disease. The highest dose of 1.0 mg/kg resulted in a mean LDL-C reduction of 62% and lowered the PCSK9 protein by 88%. These effects have been sustained for up to 18 months, and the treatment was well-tolerated with no serious adverse events.
The data positions Eli Lilly (NYSE: LLY) to compete with established PCSK9 inhibitors like Amgen’s Repatha, which require repeat injections. By offering a potential one-time fix for a lifelong condition, VERVE-102 could transform cardiovascular care from chronic management to a single-treatment event, with Lilly planning to begin a Phase 2 trial by the end of the year.
VERVE-102 is an in vivo base editing medicine, a type of gene editing that precisely changes a single letter in the DNA without making a double-strand break in the helix. The therapy, administered as a single intravenous infusion, is designed to permanently turn off the PCSK9 gene in the liver. People born with a natural loss-of-function variant of this gene have low LDL-C for life and a markedly lower risk of heart attacks.
The approach differs from existing treatments like statins or injectable PCSK9 inhibitors, which face challenges with patient adherence. "We know that up to half of patients are not taking these therapies after one year," Scott Vafai, chief medical officer at Verve Therapeutics, a wholly-owned subsidiary of Lilly, told Fierce Biotech. A one-time treatment would eliminate this issue, which is a significant factor in real-world efficacy.
The efficacy of VERVE-102 appears competitive with current market leaders. Amgen's Repatha showed cholesterol reductions between 50% and 60% in its pivotal trials. VERVE-102’s 62% reduction at its highest dose clears that bar, with the added benefit of durable, stable lowering without the cholesterol level fluctuations sometimes seen between doses of chronic therapies.
Lilly is advancing into a competitive field, with companies like CRISPR Therapeutics and Scribe Therapeutics also developing gene-editing solutions for cardiovascular disease. However, Verve executives believe their base editing approach, which avoids cutting the DNA’s double helix, minimizes the risk of unintended genetic changes. The U.S. Food and Drug Administration has granted Fast Track designation for VERVE-102.
This article is for informational purposes only and does not constitute investment advice.
