Verve Therapeutics Reports Positive Data from Heart-2 Phase 1b Trial of VERVE-102

Verve Therapeutics, a clinical-stage company focused on genetic medicines for cardiovascular disease, has released promising initial results from its Heart-2 Phase 1b clinical trial of VERVE-102. The trial targets patients with heterozygous familial hypercholesterolemia (HeFH) or premature coronary artery disease (CAD), populations that require significant and lasting reductions in low-density lipoprotein cholesterol (LDL-C). The study, conducted across various dose levels, showed that VERVE-102 is well-tolerated and effective in lowering LDL-C.

A total of 14 participants were enrolled in the Heart-2 study, which is an open-label, single-ascending dose trial. The objective was to assess the safety and tolerability of VERVE-102 in patients who need further LDL-C reduction. VERVE-102 uses a unique GalNAc-LNP delivery system and is designed as a one-time treatment that deactivates the PCSK9 gene in the liver, thus reducing LDL-C. The results demonstrated a clear dose-dependent reduction in both LDL-C and PCSK9 protein levels.

In the trial, participants received single infusions of VERVE-102 at different dose levels: 0.3 mg/kg, 0.45 mg/kg, and 0.6 mg/kg. The participants showed a mean reduction in LDL-C of 53%, with a maximum reduction of 69% observed in the 0.6 mg/kg dose group. Importantly, VERVE-102 was well-tolerated, with no treatment-related serious adverse events and no significant changes in laboratory markers such as ALT or platelets.

Dr. Eugene Braunwald, a distinguished professor of medicine, expressed optimism about the findings, citing the potential for VERVE-102 to transform cardiovascular disease treatment by offering a single-dose solution for cholesterol management. This could significantly improve patient adherence, as many currently discontinue conventional therapies within a year.

VERVE-102 is a novel investigational medicine that utilizes base editing technology to permanently turn off the PCSK9 gene, crucial for lowering LDL-C levels. The drug consists of an adenine base editor and a guide RNA encapsulated in lipid nanoparticles, administered via a single intravenous infusion. The Heart-2 trial is designed to evaluate both the safety and various pharmacokinetic parameters of this innovative treatment.

The trial includes four dose cohorts, each with three to nine participants diagnosed with HeFH or premature CAD. As of the latest update, data are available from 14 participants in the first three cohorts. The treatment has shown no dose-limiting toxicities or cardiovascular events, reinforcing its potential as a safe therapeutic option.

VERVE-102's efficacy was analyzed by measuring changes in LDL-C and PCSK9 levels from baseline. In the first cohort (0.3 mg/kg), LDL-C was reduced by 21%, while the second cohort (0.45 mg/kg) saw a reduction of 41%. The third cohort (0.6 mg/kg) achieved a 53% reduction, highlighting the dose-dependent nature of the response.

Verve Therapeutics is currently enrolling participants in the fourth dose cohort of 0.7 mg/kg in several countries, including the UK, Canada, and Australia. The company is on track to release final data from the dose escalation phase in the second half of 2025. Plans are also underway to initiate a Phase 2 clinical trial, pending regulatory approval.

With the advancements in VERVE-102, Verve Therapeutics aims to address the unmet need for effective and lasting cholesterol reduction. The company has partnered with Eli Lilly and Company, which may opt to collaborate further on the PCSK9 program. Verve's innovative approach holds promise for revolutionizing treatment for patients with hypercholesterolemia and atherosclerotic cardiovascular disease, potentially eliminating the need for chronic medication regimens.