Verve Therapeutics has received clearance from the U.S. Food and Drug Administration (FDA) to expand its gene editing trial for a novel cholesterol treatment into the United States, the company announced Monday. The experimental therapy, VERVE-102, employs a cutting-edge base editing technique to permanently modify the PCSK9 gene, potentially offering a one-time treatment for patients with persistently high cholesterol levels.
VERVE-102 works by changing a single nucleotide in the PCSK9 gene, which produces a protein that regulates how liver cells absorb cholesterol from the bloodstream. By deactivating this gene in liver cells, the treatment aims to provide lifelong cholesterol reduction after a single administration.
Target Population and Clinical Need
The therapy is being tested in patients with heterozygous familial hypercholesterolemia (HeFH), an inherited condition causing persistently elevated cholesterol levels, or those with premature coronary artery disease. These patients often struggle to achieve target cholesterol levels despite available treatments.
"There are multiple cholesterol lowering medicines currently available that can lower LDL-C at a single time point; however, time on treatment for these medicines remains low," said Sekar Kathiresan, CEO of Verve Therapeutics, in a statement. "To address this unmet need, Verve's medicines are designed to deliver lifelong cholesterol lowering after a single course of treatment and, consequently, drive more meaningful efficacy."
Current Trial Status and Timeline
Verve has been conducting a Phase 1b trial called Heart-2 in Australia, New Zealand, Canada, and the United Kingdom. With FDA clearance, this trial will now expand to include U.S. sites. The company expects to announce initial safety and efficacy data before the end of June 2024, with dose escalation data and the initiation of a Phase 2 clinical trial planned for later this year.
Competitive Landscape in PCSK9 Inhibition
The PCSK9 pathway is already targeted by several approved therapies, including antibody drugs and RNA medicines. Amgen's Repatha (evolocumab), the market leader in this category, generated over $2.2 billion in revenue in 2024. Other competitors include Sanofi/Regeneron's Praluent (alirocumab) and Novartis's Leqvio (inclisiran).
However, these existing treatments require regular administration—ranging from injections every two weeks to every six months. VERVE-102, by contrast, aims to provide a permanent solution with a single treatment course by directly editing the gene responsible for cholesterol regulation.
Evolution from Earlier Therapy
VERVE-102 represents an evolution from the company's earlier treatment, VERVE-101, which was the first base editing therapy to be tested in humans. Verve paused the VERVE-101 trial last year after a participant developed elevated liver enzymes and reduced platelet counts (thrombocytopenia).
While both treatments use similar mechanisms to target the PCSK9 gene, VERVE-102 employs a different lipid nanoparticle for delivery into the body. The company had previously suggested that the lipid nanoparticle used in VERVE-101 may have contributed to the adverse events observed.
Base Editing Technology
Base editing represents a refinement of CRISPR gene editing technology. Unlike traditional CRISPR approaches that create double-strand breaks in DNA, base editing replaces single nucleotides without breaking both DNA strands. This precision potentially reduces the risk of unwanted insertions, deletions, or DNA rearrangements that can occur with conventional gene editing methods.
Future Prospects and Pipeline
Beyond VERVE-102, the company has disclosed two additional base editing therapies, with one already in Phase 1 testing. Verve has also established a partnership with pharmaceutical giant Eli Lilly, which has the option to share development costs and profits for VERVE-102 after reviewing data from the Heart-2 trial.
If successful, Verve's approach could fundamentally change cardiovascular disease management by offering a one-time treatment that provides lifelong cholesterol control, addressing the persistent challenges of medication adherence and chronic therapy management that limit the effectiveness of current treatments.
The expansion of the VERVE-102 trial into the U.S. marks a significant milestone for both the company and the broader field of in vivo gene editing, potentially bringing this innovative therapeutic approach closer to patients with difficult-to-treat cholesterol disorders.
