In a Phase Ib trial, VERVE-102 showed it could lower bad cholesterol across doses, setting up an opt-in decision for Eli Lilly and a showdown with Novartis.
Verve Therapeutics’ in vivo base editing therapy, VERVE-102, lowered bad cholesterol in Phase Ib, the company announced Monday morning, leaving the company’s partner, Eli Lilly, with a decision to make.
Analysts from both William Blair and BMO Capital Markets pointed to the asset’s “clean” safety profile in notes to investors Monday morning. Safety was the trial’s primary outcome.
VERVE-102 targets and permanently shuts off the PCSK9 gene specifically in the liver, with the aim of reducing low-density lipoprotein cholesterol (LDL-C, so-called “bad” cholesterol) to treat heterozygous familial hypercholesterolemia (HeFH), where high cholesterol can lead to strokes and heart attacks.
The therapy is part of a $60 million deal with Eli Lilly signed in 2023, where the larger pharma can opt-in to take over development of the therapy after Phase I trials are completed.
VERVE-102 showed dose-dependent reductions in LDL-C, with the lowest dose eliciting a 21% average reduction while the highest led to a 53% reduction, with one patient in the highest dose cohort seeing a 69% reduction.
These data from the highest-dose cohort “numerically [beat] the LDL-C lowering bar for a long-acting PCSK9 inhibitor set by [Novartis’] Leqvio,” which elicited a 39.7% LDL-C lowering for HeFH patients, William Blair analysts said Monday. Verve could also differentiate itself from Leqvio in another way: VERVE-102 is a one-time therapy, while Leqvio is given twice per year.
Verve reported “no treatment-related [serious adverse effects], no dose-limiting toxicities, and no cardiovascular events observed,” according to its press release.
“We believe the absence of dose-dependent changes in [adverse effects] points to a wide VERVE-102 therapeutic index,” BMO wrote.
VERVE-102’s continuing development sets it up for a showdown with Leqvio, an siRNA treatment that also targets PCSK9. Novartis licensed the drug from Alnylam in 2020, winning FDA approval in 2021. The William Blair analysts also compared VERVE-102 to Merck’s investigational PCSK9 drug MK-0616, which has achieved similar LDL-C-lowering numbers, while noting that food consumption lowers its bioavailability. AstraZeneca also has a drug candidate in the running, AZD0780, though William Blair noted that daily dosing might be a disadvantage.
Monday’s results may come as a relief to Verve. A year ago, the company halted development of a similar PCSK9 gene editor, VERVE-101, due to Grade 3 drug-induced thrombocytopenia. The company at the time attributed those abnormalities to the lipid nanoparticle delivery system used by VERVE-101. Verve then pivoted to VERVE-102, which uses a different nanoparticle. Two months ago, Vertex severed a $400 million agreement signed with Verve in 2022 to co-develop gene therapies together.
