Dive Brief:

• Verve Therapeutics has treated the first participant in a recently begun clinical trial of the company’s backup gene editing therapy for heart disease, about one month after a safety setback derailed what had been its lead candidate.
• The Phase 1b study, dubbed Heart-2, is testing Verve’s therapy in people with a hereditary form of high cholesterol known as HeFH for short, or who have premature coronary artery disease. The company is currently cleared to enroll patients in the U.K. and Canada, although it eventually plans to expand the study to the U.S.
• Verve’s therapy uses a technique called base editing to change a single nucleotide, or base, in a liver gene called PCSK9. The effect is inactivation of the gene and, in theory, permanent lowering in LDL cholesterol, high levels of which are closely linked to heart disease.

Dive Insight:

Verve had been steadily progressing its lead base editing therapy Verve-101, enrolling patients with HeFH across three countries and, last November, revealing data that offered “proof of principle” for its treatment approach.

But early last month, the company disclosed concerning laboratory test results for one participant, which showed elevated liver enzyme counts and lower levels of a clot-forming blood cell. The participant was observed in a hospital and released after the abnormalities resolved.

Since the irregularities occurred shortly after treatment with Verve-101, however, investigators judged the side effect as likely to be treatment induced. High counts in certain liver enzymes can be a warning sign of organ damage.

In response, Verve paused study enrollment while it investigates the side effect and pivoted its efforts to Verve-102 instead.

The two treatments are designed to shut off the PCSK9 gene in the same way, but Verve-102 uses a different lipid nanoparticle “shell” to deliver the gene editing components into the body and to the right cells. The company says the lipid nanoparticle used in Verve-101 may be the cause of the side effect it observed.

The shell for Verve-102 also enables the therapy to enter cells by two different receptors, potentially allowing Verve to test lower doses and avoid other side effects.

According to Verve, the Heart-2 trial will study Verve-102’s safety as well as its effects on blood PCSK9 protein and LDL cholesterol levels. The study will involve four dose cohorts, each enrolling three to nine patients with HeFH, heterozygous familial hypercholesterolemia, or premature coronary artery disease.

Verve expects to report results from the trial in 2025.