Verve Therapeutics Halts Enrollment of Heart-1 PCSK9 Gene Therapy Trial

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Verve Therapeutics announced plans to voluntary pause enrollment of the Heart-1 trial, citing an adverse event and consultation with DSMB, with plans to shift focus to VERVE-102 and Heart-2 trial.

Verve Therapeutics announced it would be halting enrollment in its Heart-1 trial following an adverse event in the trial’s 6th patient dosed with VERVE-101 0.45 mg/kg dose and subsequent consultation with the independent data safety and monitoring Board.

Announced by Verve Therapeutics on April 2, 2024, the press release indicates the patient experienced a Grade 3 drug-induced transient increase in ALT a d a Grade 3 drug-induced thrombocytopenia within the first 4 days after dosing with the 0.45 mg/kg dose of VERVE-101. A decision that comes less than 5 months after the phase 1b trial stole headlines alongside SELECT and other late-breakers at the American Heart Association’s Scientific Sessions 2023, the company now intends to prioritize the development of VERVE-102 and the initiation of the Heart-2 clinical trial.1,2

“The Heart-1 study continues to support proof-of-concept for in vivo base editing of the PCSK9 gene in the liver, with a meaningful and durable lowering of LDL-C,” said Sekar Kathiresan, MD, co-founder and chief executive officer of Verve Therapeutics.1 “However, at potentially therapeutic dose levels of VERVE-101, we have observed certain asymptomatic laboratory abnormalities, which we believe are attributable to the LNP delivery system. The safety of patients in our clinical trials is of the utmost importance. We plan to further investigate the laboratory abnormalities observed in the Heart-1 study in order to inform the next steps for VERVE-101.”

At AHA 2023, Andrew Bellinger, MD, PhD, chief scientific officer of Verve Therapeutics, presented interim data from the heart-1 trial. A first-in-human trial of patients with heterozygous familial hypercholesterolemia (HeFH), Bellinger presented data from 10 participants across 4 dose cohorts: 0.1 mg/kg (n = 3), 0.3 mg/kg (n = 3), 0.45 mg/kg (n = 3), and 0.6 mg/kg (n = 1). With a data cutoff of October 16, 2023, results of the trial pointed to an LDL-C reduction of 55% with just a single treatment at the greatest dose.2

In their April 02, 2024 announcement, Verve Therapeutics underlined all safety events were reported to regulatory agencies in the US, New Zealand, and the UK. The company pointed out the Investigational New Drug Application and other CTAs for VERVE-101 remain active at this time.1

Of note, the patient did not experience any bleeding or other symptoms related to the aforementioned abnormalities and the abnormalities full resolved within a few days.1

Like VERVE-101, VERVE-102 leverages a the same base editor and guide RNA for PCSK9, but uses a different lipid nanoparticle delivery system. Verve Therapeutics highlighted 2 key differences in the therapies in their release:1

  • VERVE-102 includes a different ionizable lipid from VERVE-101, which has been shown in previous trials to be well-tolerated.
  • Incorporation of GalNAc allows the LNP in VERVE-102 to access liver cells using either the asialoglycoprotein receptor or the low-density lipoprotein receptor (LDLR), whereas VERVE-101 only accesses liver cells through the LDLR.

Verve Therapeutics highlighted receipt of regulatory clearances for the Heart-2 trial, which will include patients with HeFH or premature coronary artery disease, in the UK and Canada, with plans to launch the trial in Q2 2024.1

“At this time, we are prioritizing the initiation of the Heart-2 clinical trial of VERVE-102 due to its proximity to the clinic and its use of a different LNP that incorporates an ionizable lipid which has been well-tolerated in third-party clinical trials,” Kathiresan said.1 “We are grateful to our study participants and to our investigators, who share our belief in the promise of single-course gene editing medicines for the treatment of cardiovascular disease. We look forward to initiating the Heart-2 trial in the second quarter of this year.”


  1. Verve therapeutics announces updates on its PCSK9 program. Verve Therapeutics. April 2, 2024. Accessed April 2, 2024.
  2. Johnson V. CRISPR editing therapy reduces LDL-C in familial hypercholesteremia in small trial. CGTlive. November 27, 2023. Accessed April 2, 2024.