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Verve Therapeutics saw its stock surge by more than 26% when markets opened today (14 April) after the company announced early-stage clinical data for its Eli Lilly-partnered experimental gene editing therapy VERVE-102.
The company reported encouraging safety and efficacy from the Phase Ib Heart-2 trial (NCT06164730), which is testing the one-time treatment in patients with heterozygous familial hypercholesterolaemia (HeFH) and/or premature coronary artery disease (CAD).
Patients with these disorders are at high risk of cardiovascular events due to elevated low-density lipoprotein cholesterol (LDL-C) levels. VERVE-102 uses a CRISPR base-editing system to permanently deactivate the PCSK9 gene in liver cells. This increases the number of LDL receptors and lowers LDL-C levels.
In April 2024, Verve halted enrolment into its Heart-1 trial (NCT05398029) investigating VERVE-101 – another gene editing therapy targeting PCSK9 – after a patient experienced elevated liver enzyme levels and low platelet levels. The adverse effects were linked to the lipid nanoparticle delivery system used to deliver the genetic payload. Among the 13 patients enrolled, six were dosed at 0.45 mg/kg, with the sixth patient showing abnormal lab results within four days of treatment. Verve announced that it would prioritise the development of VERVE-102 following these safety issues.
Against this backdrop, the latest VERVE-102 data appears to signal progress. No treatment-related serious adverse events or clinically significant laboratory abnormalities were noted in the Heart-2 trial. Key safety markers, including liver enzymes and platelet counts, remained within normal limits across all dose levels.
In the highest dose group of 0.6 mg/kg, the therapy achieved a mean reduction in LDL-C of 53%, with one participant reaching a maximum reduction of 69%. The trial enrolled 14 participants who received a single infusion of VERVE-102 across three escalating dose cohorts.
Verve’s CEO Sekar Kathiresa said: “The initial efficacy data suggest that VERVE-102 has the potential to match or exceed the LDL-C reduction provided by currently available PCSK9-targeting therapies.”
Among these PCSK9-targeting therapies is Novartis’s Leqvio (inclisiran), Amgen’s Repatha (evolocumab), and Regeneron’s Praluent (alirocumab). However, none of these therapies offer the single-dose approach that Verve is putting forward.
“Verve was founded seven years ago with a vision of one treatment dose potentially leading to a lifetime of LDL-C lowering. The data presented today suggest that this game-changing, one dose future is possible,” added Kathiresa in the 14 April announcement.