FDA Clears IND Application for VERVE-102 Gene Therapy for HeFH

The US Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for VERVE-102, a gene editing medicine targeted for the treatment of heterozygous familial hypercholesterolemia (HeFH) and/or premature coronary artery disease (CAD).1

Announced by Verve Therapeutics on March 24, 2025, the novel in vivo base editing therapy is designed as a single-course dose intended to inhibit the PCSK9 gene to durably lower blood low-density lipoprotein cholesterol (LDL-C).

“The IND clearance from the US FDA represents an important step in our journey to advance a new class of in vivo gene editing medicines for people worldwide living with cardiovascular disease,” said Sekar Kathiresan, MD, co-founder and chief executive officer of Verve Therapeutics.1 “There are multiple cholesterol-lowering medicines currently available that can lower LDL-C at a single time point; however, time on treatment for these medicines remains low.”

VERVE-102 is in development initially for HeFH, with an ultimate goal to treat patients with established atherosclerotic cardiovascular disease (ASCVD) who continue to be impacted by high LDL-C levels. In the IND submission, the company provided interim data from the dose–escalation part of the ongoing Phase 1b Heart-2 clinical trial.2

Heart-2 examined the safety and tolerability of VERVE-102 in individuals with HeFH and/or premature CAD, including additional analyses for pharmacokinetics and changes in blood PCSK9 protein and LDL-C levels. At the cutoff date of January 2025, trial data submitted to the FDA included participants across 3 dose cohorts: 0.3 mg/kg, 0.45 mg/kg, and 0.6 mg/kg.1

At the cutoff point, Verve Therapeutics reported VERVE-102 was well-tolerated, without treatment-related serious adverse events and no observed clinically significant laboratory abnormalities. The company expects demographic and initial safety and efficacy data from Heart-2 to be reported in the second quarter of 2025, with ≥28 days of follow-up for each participant.

Verve Therapeutics also announced it remains on track to report final data from the dose-escalation portion of Heart-2, submit the opt-in data package for the PCSK9 program to Eli Lilly and Company, and initiate the Phase 2 clinical trial for the PCSK9 program.

“With our ongoing Heart-2 clinical trial for VERVE-102 progressing internationally, we are excited to begin activating trial sites in the U.S. as we expect it to play a key role in our continued clinical development,” Kathiresan said.1

Verve’s other lead genetic medicine programs each target cholesterol drivers of atherosclerosis, including emnant cholesterol and Lipoprotein(a) [Lp(a)]. VERVE-201 is targeted to permanently shut off the ANGPTL3 gene in patients with refractory hypercholesterolemia with high LDL-C, despite maximally tolerated standard of care therapy, and homozygous familial hypercholesterolemia (HoFH).3

VERVE-301 is designed to permanently turn off the LPA gene to reduce levels of Lp(a), an independent risk factor for ASCVD, ischemic stroke, thrombosis, and aortic stenosis.3

References

1. Verve therapeutics announces clearance of Investigational New Drug Application by the U.S. FDA for Verve-102, an investigational gene editing medicine designed to durably lower cholesterol after a single dose. Verve Therapeutics. March 24, 2025. Accessed March 25, 2025. https://ir.vervetx.com/news-releases/news-release-details/verve-therapeutics-announces-clearance-investigational-new-0.

2. Our PCSK9 programs we are developing two product candidates targeting PCSK9 – verve-101 and verve-102. these single-course treatments are designed to permanently inactivate the PCSK9 gene in the liver to reduce disease-driving LDL-C. Verve 101 & 102 | Verve Therapeutics. Accessed March 25, 2025. https://www.vervetx.com/our-programs/verve-101-102.

3. Our ANGPTL3 program we are developing Verve-201, a single-course base editing medicine, to permanently inactivate the ANGPTL3 gene in the liver to reduce disease-driving LDL-C in people with cardiovascular disease. Verve 201 | Verve Therapeutics. Accessed March 25, 2025. https://www.vervetx.com/our-programs/verve-201.