A one-time treatment for patients at risk of heart disease is one step closer to the clinic as Verve Therapeutics announced positive initial data from the Heart-2 Phase Ib clinical trial of VERVE-102 this week. A single infusion of VERVE-102 produced dose-dependent decreases in blood PCSK9 protein levels and LDL-C, with a mean reduction in blood LDL-C of 53% and a maximum LDL-C reduction of 69% observed among four participants in the 0.6 mg/kg dose cohort.
VERVE-102 is a novel, in vivo, investigational base editing medicine designed to be a single-course treatment that permanently turns off the PCSK9 gene in the liver and durably reduces disease-driving LDL-C.
The current trial is evaluating patients with heterozygous familial hypercholesterolemia (HeFH) and/or premature coronary artery disease (CAD), two sets of patients that require deep and durable reduction of blood low-density lipoprotein cholesterol (LDL-C) levels. It was a small trial, but among 14 participants across three dose levels, VERVE-102 was well-tolerated and no clinically significant laboratory abnormalities were observed.
“These initial Heart-2 data are promising with respect to both safety and efficacy and suggest the potential for a new era of cardiovascular disease treatment where a single dose might lead to lifelong control of LDL-C,” said Eugene Braunwald, MD, Distinguished Hersey Professor of Medicine at Harvard Medical School and founding chairman, TIMI Study Group, Brigham and Women’s Hospital.
He added, “Despite existing treatments to lower LDL-C, atherosclerotic cardiovascular disease (ASCVD) remains the most frequent cause of death worldwide. The reduction of ASCVD risk depends on both the magnitude of LDL-C reduction as well as the duration. With existing treatments, approximately half of patients discontinue their prescribed lipid lowering therapy within one year, resulting in poor real-world control of LDL-C. VERVE-102 holds great promise to transform the care of ASCVD and move that care from daily pills or intermittent injections over decades to a one dose future for sustained LDL-C lowering.”
VERVE-102 is designed to be a single-course treatment that permanently turns off the PCSK9 gene in the liver and durably reduces disease-driving LDL-C. The treatment consists of an adenine base editor and a guide RNA (gRNA) targeting the PCSK9 gene. Both are encapsulated in a lipid nanoparticle (LNP) and administered as a single intravenous infusion over two to four hours. Across all 14 participants, the drug demonstrated a strong dose-dependent response between the amount of total RNA administered and LDL-C reductions.
“Verve was founded seven years ago with a vision of one treatment dose potentially leading to a lifetime of LDL-C lowering. The data presented today suggest that this game-changing, one dose future is possible,” said Sekar Kathiresan, MD, co-founder and CEO of Verve Therapeutics.
As a next step, the Heart-2 clinical trial of VERVE-102 is enrolling participants, who will receive a slightly higher dose, in the United Kingdom, Canada, Israel, Australia, and New Zealand. Verve plans to dose the first patient in the Phase II trial in the second half of 2025.
