Lilly's VERVE-102 Base Editor Cuts LDL Cholesterol by 62% in Phase 1b Trial, Results Published in NEJM

Overview

Eli Lilly on May 25, 2026, announced Phase 1b results for VERVE-102, an investigational gene-editing therapy that silences a cholesterol-regulating gene in the liver with a single infusion. At the highest dose tested, the drug reduced levels of the PCSK9 protein by up to 88% and low-density lipoprotein cholesterol (LDL-C) by up to 62%, with effects held stable for up to 18 months, according to the Lilly press release. Results were presented as a late-breaking oral presentation at the 94th European Atherosclerosis Society (EAS) Congress in Athens, Greece and simultaneously published in The New England Journal of Medicine.

What We Know

The drug and its mechanism. VERVE-102 is described by Lilly as “an investigational in vivo base editing medicine designed to durably turn off the PCSK9 gene in the liver,” according to the Lilly press release. Rather than cutting DNA like conventional CRISPR-Cas9, base editing makes a single-letter change in the genetic code — in this case rewriting a nucleotide in the PCSK9 gene to permanently reduce production of the PCSK9 protein. PCSK9 regulates LDL clearance from the bloodstream, and its inhibition is already the target of injectable antibody drugs; VERVE-102 aims to achieve a similar effect with one treatment instead of recurring injections. The drug is delivered via a single intravenous infusion lasting approximately four hours using lipid nanoparticle (LNP) technology, as detailed by Lilly.

Trial design. The Heart-2 Phase 1b study enrolled 35 adults with heterozygous familial hypercholesterolemia (HeFH) or premature coronary artery disease (CAD), according to Lilly. Six ascending dose cohorts were tested: 0.3, 0.45, 0.6, 0.7, 0.8, and 1.0 milligrams per kilogram of body weight. The interim analysis covers all 35 participants, with a median follow-up of approximately nine months and 15 participants followed for at least one year, as reported by BioSpace.

Efficacy results. Reductions in PCSK9 ranged from 51% at the lowest dose (0.3 mg/kg) to 88% at the highest (1.0 mg/kg), with corresponding LDL-C reductions of 9% and 62%, respectively, per Lilly. Reductions were sustained over time, with durability observed for up to 18 months in the earliest-treated participants, according to Investing News Network. All 35 participants received their full planned dose and none withdrew from the study, as noted by Lilly.

Safety profile. The drug was well tolerated across all dose levels, with no treatment-related serious adverse events and no dose-limiting toxicities reported, according to BioSpace. Adverse events were limited to low-grade infusion-related reactions and fatigue. STAT News noted the safety results are “a notable finding, given that Verve had to shelve its first candidate due to safety concerns,” referring to VERVE-101, the predecessor compound that did not advance due to toxicity issues observed in earlier testing.

Regulatory status and next steps. The FDA has granted Fast Track designation to VERVE-102, according to Lilly. Lilly plans to initiate the Phase 2 clinical study of VERVE-102 by the end of 2026, as reported by BioPharma Dive.

Executive perspective. Sekar Kathiresan, Lilly’s senior vice president who previously founded Verve Therapeutics, stated: “The Heart-2 results provide early clinical evidence that a single dose of VERVE-102 may mimic the LDL-C lowering effects,” referencing naturally occurring protective gene variants that confer lifetime low cholesterol in some individuals, as quoted by BioSpace.

Acquisition background. VERVE-102 entered Lilly’s portfolio through its acquisition of Verve Therapeutics, a Boston-based clinical-stage company, announced on June 17, 2025, for an upfront payment of approximately $1.0 billion ($10.50 per share in cash), with contingent value rights worth up to an additional $3.00 per share — bringing the total potential consideration to approximately $1.3 billion — per the Lilly acquisition press release. At the time of the deal, Ruth Gimeno, Lilly’s group president for cardiometabolic health, said VERVE-102 “has the potential to be the first in vivo gene editing therapy for broad patient populations and could shift the treatment paradigm for cardiovascular disease from chronic care to one-and-done treatment,” according to the acquisition press release.

What We Don’t Know

The Heart-2 data are interim Phase 1b results from 35 patients — a small number insufficient to draw conclusions about long-term efficacy or safety. Whether the LDL reductions observed at one year will hold at two, five, or ten years remains unknown; Lilly has announced a long-term follow-up study but has not yet reported results beyond 18 months. The trial population had genetically elevated cholesterol or early-onset heart disease, so whether the drug will perform similarly in a broader population with standard risk profiles is not established.

The relationship between PCSK9 and LDL-C reduction was not linear across all dose cohorts in the Heart-2 data — the 0.7 mg/kg cohort showed 33% LDL-C reduction despite 60%+ PCSK9 reductions, per Lilly. The reasons for this non-monotonic LDL response have not been disclosed.

HeFH affects approximately 1 in 250 people, per the acquisition press release, and cardiovascular disease is described by executives as “the world’s leading killer,” according to STAT News. Whether VERVE-102 will eventually receive approval for a broad population — not just high-risk genetic cases — depends on yet-to-be-run Phase 2 and Phase 3 trials.

Analysis

The Heart-2 interim results push in vivo base editing meaningfully closer to cardiovascular clinical practice. Base editing’s appeal over conventional CRISPR lies in its precision: rather than introducing a double-strand DNA break that requires the cell’s repair machinery, a base editor chemically converts one DNA letter to another, reducing the risk of unintended insertions, deletions, or chromosomal rearrangements. For a drug targeting a gene that millions of people might one day take — if efficacy is confirmed in larger trials — that safety margin matters substantially.

The 18-month durability observation is encouraging for the one-shot hypothesis, but the duration required to claim durable benefit in a cardiovascular context is measured in decades. LDL-lowering drugs are assessed against outcomes like heart attack and stroke rates over years of treatment. VERVE-102 is still far from that bar: Phase 2 has not yet started, and Phase 3 would likely need to enroll thousands of patients and follow them for years.

The clean safety profile in 35 patients addresses one specific concern raised by VERVE-101, the predecessor compound that was discontinued. Whether the LNP delivery system and the base editing mechanism will remain well tolerated at Phase 2 and 3 scale — and in a broader patient population — is a question the coming trials will need to answer.