No treatment-related adverse events have been reported and Verve expects a letter detailing the hold within 30 days.
The FDA has placed a clinical hold on Verve Therapeutics’ heart-1 clinical trial of VERVE-101, a gene-editing therapy for the potential treatment of heterozygous familial hypercholesterolemia (HeFH).1
“We founded Verve with a vision of providing patients with ASCVD a transformative alternative to the current chronic care management system,” Sekar Kathiresan, MD, co-founder and chief executive officer, Verve, said in a statement.1 “We prepared a comprehensive regulatory package for VERVE-101, a first-in-class in vivo liver base editing program, that we submitted to the FDA in October. We anticipate receiving details from the FDA in the next month, and are committed to working closely with the Agency to address their questions, so that we may open enrollment for patients with HeFH in the U.S.”
Verve submitted its investigational new drug application (IND) for VERVE-101 in October 2022 and received notification of the hold on Friday, November 4, 2022. The company expects to receive an official letter detailing the hold within 30 days and will work with the FDA and provide updates on the hold when possible.
Verve has reported no sudden unexpected serious adverse events (AEs) in the heart-1 study. The first dose cohort has completed dosing in the dose-escalation portion of the trial and the 3 patients treated have tolerated the therapy well, with no treatment-related AEs reported so far. AEs were all grade 1. The independent Data Safety Monitoring Board (DSMB) has recommended dose escalation to the second dose level, expected to begin soon, after reviewing safety data from the first cohort.
Enrollment in the heart-1 trial continues in New Zealand and the UK, from which data were not included in the submitted IND. Verve plans to report further safety and pharmacodynamic data for all dose cohorts at a medical meeting in the second half of 2023. The company dosed the first participant in New Zealand in July 2022.2
“We are pleased to have completed dosing in the first dose cohort of the heart-1 trial and to have received a recommendation by an independent DSMB to move to the second dose level,” Andrew Bellinger, MD, PhD, chief medical and scientific officer, Verve, added to the statement.1 “The safety profile observed in the first dose cohort with VERVE-101 is encouraging, and in-line with safety data generated with VERVE-101 in our preclinical studies. Enrollment efforts for the second dose cohort continue in New Zealand and the U.K.”