Verve Therapeutics Reports Promising Safety Profile for PCSK9 Gene Editing Candidate

Verve Therapeutics has unveiled encouraging safety data for its second-generation PCSK9 gene editing candidate, VERVE-102, potentially paving the way for a significant breakthrough in cholesterol management. The Boston-based biotech company's latest results suggest that its strategic pivot following earlier setbacks may yield substantial dividends in the competitive landscape of cardiovascular therapeutics.

VERVE-102 Demonstrates Clean Safety Profile

In a phase 1b trial involving 14 patients with heterozygous familial hypercholesterolemia and/or premature coronary artery disease, VERVE-102 showed no clinically significant changes in key safety markers. The trial, which tested three different doses of the gene editing candidate, reported no dose-dependent trends in laboratory measurements, addressing previous concerns that led to the discontinuation of its predecessor, VERVE-101.

The most notable adverse event was a grade 2 infusion-related reaction in one patient, which resolved with acetaminophen treatment. Importantly, there were no treatment-related serious adverse events, dose-limiting toxicities, or cardiovascular events reported across the cohorts.

Efficacy Data Signals Potential for Durable Cholesterol Reduction

While safety was the primary focus, VERVE-102 also demonstrated promising efficacy. At the 0.45 mg/kg dose, patients experienced a 41% reduction in LDL cholesterol and a 53% reduction in PCSK9 levels, averaged from Day 28 through the last follow-up. These results are comparable to those seen with VERVE-101, suggesting that the new lipid nanoparticle (LNP) formulation has not compromised the treatment's effectiveness.

Even more encouraging, the 0.60 mg/kg dose group showed time-averaged reductions of 53% in LDL-C and 60% in PCSK9. This dose-dependent response has prompted Verve to initiate enrollment for a higher 0.7 mg/kg dose cohort, with early data from two patients aligning with the safety profile observed in lower dose groups.

Next Steps and Potential Industry Impact

Verve Therapeutics is now poised to advance VERVE-102 into phase 2 trials, with the first patient expected to be dosed in the second half of 2025. The company plans to expand its trial sites to include the United States, following recent FDA clearance.

The success of VERVE-102 could have significant implications for Eli Lilly, which acquired an opt-in right for the program from Beam Therapeutics in 2023. Verve plans to present Lilly with the opt-in package in the latter half of 2025, potentially leading to a collaborative development and commercialization effort in the U.S. market.

As the pharmaceutical industry continues to seek innovative approaches to managing cholesterol levels, VERVE-102's potential for providing durable LDL-C reductions after a single dose sets it apart from current market offerings like Amgen's Repatha and Sanofi/Regeneron's Praluent. With AstraZeneca and Merck & Co. also developing oral PCSK9 inhibitors, the race to dominate this therapeutic space is intensifying, making Verve's progress a critical development to watch in the coming years.