NEW YORK – Promising data on Verve Therapeutics' base-editing heart disease treatment within a Phase I study has bolstered its plans for a Phase II clinical trial later this year.
The Boston-based company announced Monday that it hopes to start dosing patients with the PCSK9-targeted treatment, VERVE-102, in a planned Phase II study at US trial sites in the second half of 2025 if the US Food and Drug Administration clears its investigational new drug (IND) application.
These plans follow emerging data on VERVE-102 from the Heart-2 Phase Ib trial underway outside the US, in which the company has tested the ability of the drug to lower low-density lipoprotein cholesterol (LDL-C) and PCSK9 in 14 patients with heterozygous familial hypercholesterolemia or premature coronary disease across three dose levels.
Patients in the Heart-2 trial tolerated VERVE-102 well and experienced no treatment-related serious adverse events (SAEs) and had no clinically significant laboratory abnormalities. Treatment with VERVE-102 at the highest dose reduced LDL-C levels by 53 percent and PCSK9 by 60 percent. One patient saw their LDL-C level go down by 69 percent on the highest dose, according to Verve.
"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," Verve CEO and Cofounder Sekar Kathiresan said in a statement.
Verve is now enrolling patients in a fourth dosing cohort in the Phase Ib Heart-2 trial at sites in the UK, Canada, Israel, Australia, and New Zealand. It has enrolled two patients in this cohort as of April 7, and the early lab data and safety profile appear in line with what researchers have seen in the other dosing cohorts. The company recently garnered IND clearance from the FDA, allowing it to start enrolling patients into Heart-2 in the US. Verve will release final data from the dose-escalation portion of this study and durability data in the second half of the year.
VERVE-102 is an in vivo base-editing medicine designed to permanently turn off the PCSK9 gene in the liver and reduce LDL-C. VERVE-102 comprises an adenine base editor and a PCSK9-targeting guide RNA, which are encapsulated in a lipid nanoparticle and administered as a single intravenous infusion over several hours.
Verve is developing the PCSK9 program with Eli Lilly, which holds opt-in rights to share 33 percent of worldwide development expenses and split the costs and profits related to US commercialization. Verve controls development and commercialization of all collaboration products in the US and holds product rights outside the US. Verve said it will deliver the opt-in package for the PCSK9 program to Lilly and expects a decision from the drug giant in the second half of the year.
At the end of 2024, Verve reported it had $524.3 million in cash, cash equivalents, and marketable securities, which it said was enough capital to fund operations into mid-2027, including completing the Phase II study.