Verve's VERVE-102 Shows Promise in Cholesterol-Lowering Trial, Surpassing Competitors

Verve Therapeutics has announced promising results from its Phase Ib trial of VERVE-102, an in vivo base editing therapy designed to lower low-density lipoprotein cholesterol (LDL-C) levels. The therapy, which targets the PCSK9 gene in the liver, has demonstrated significant efficacy and a favorable safety profile, potentially positioning it as a strong competitor in the cholesterol-lowering drug market.

Trial Results and Efficacy

VERVE-102 showed dose-dependent reductions in LDL-C across all cohorts in the Phase Ib trial. The lowest dose achieved an average reduction of 21% in LDL-C levels, while the highest dose led to an impressive 53% reduction. One patient in the highest dose cohort experienced a remarkable 69% reduction in LDL-C.

These results are particularly noteworthy when compared to existing treatments. The highest-dose cohort of VERVE-102 numerically outperformed Novartis' Leqvio, which demonstrated a 39.7% LDL-C reduction in patients with heterozygous familial hypercholesterolemia (HeFH). VERVE-102's performance also appears competitive with Merck's investigational PCSK9 drug MK-0616, which has shown similar LDL-C-lowering capabilities.

Safety Profile and Therapeutic Potential

The trial's primary outcome focused on safety, and VERVE-102 delivered encouraging results. Verve reported no treatment-related serious adverse effects, no dose-limiting toxicities, and no cardiovascular events. Analysts from BMO Capital Markets noted that the absence of dose-dependent changes in adverse effects suggests a wide therapeutic index for VERVE-102.

This clean safety profile is particularly significant given Verve's previous setback with VERVE-101, a similar gene editor that was halted due to Grade 3 drug-induced thrombocytopenia. The company attributed those issues to the lipid nanoparticle delivery system used in VERVE-101 and subsequently pivoted to VERVE-102, which employs a different nanoparticle.

Market Implications and Industry Positioning

The success of VERVE-102 in this trial sets the stage for potential market disruption in the cholesterol-lowering drug sector. Unlike Leqvio, which requires twice-yearly administration, VERVE-102 is designed as a one-time therapy, offering a significant advantage in terms of patient convenience and potentially long-term efficacy.

These results also have immediate implications for Verve's partnership with Eli Lilly. The two companies entered into a $60 million deal in 2023, giving Eli Lilly the option to take over development of the therapy after the completion of Phase I trials. The positive outcomes from this Phase Ib study may influence Eli Lilly's decision to exercise this option.

The cholesterol-lowering drug market remains highly competitive, with other major players like AstraZeneca also developing candidates. AstraZeneca's AZD0780 is in the running, though analysts note that its daily dosing requirement might be a disadvantage compared to VERVE-102's one-time administration.

As Verve Therapeutics advances VERVE-102 through clinical development, the pharmaceutical industry will be watching closely to see if this innovative base editing approach can transform the treatment landscape for patients with high cholesterol and related cardiovascular risks.