Verve halts enrollment of lead trial after grade 3 side effects, prioritizing next-up PCSK9 editor

Verve Therapeutics is halting enrollment in a phase 1 study testing its lead gene editing medicine as a treatment for serious high cholesterol, pivoting to a follow-up asset that will soon launch into the clinic. 

The Boston-area biotech said Tuesday that one of the six patients treated with a 0.45-mg/kg dose of VERVE-101 experienced grade 3 increases in a particular liver enzyme and a grade 3 case of low blood platelets. The patient was hospitalized and observed for two days despite being asymptomatic.

The individual experienced no bleeding, and the lab abnormalities resolved independently within a few days, the company added.

In consultation with the trial’s data monitoring board, Verve has halted enrollment in the trial and notified regulators. The biotech is investigating the lab data and said it will work with health officials to chart a path forward for VERVE-101. In the meantime, the company is turning its attention to VERVE-102, which uses different lipid nanoparticle technology to deliver the same PCSK9 base editor as VERVE-101. 

Verve's CEO Sekar Kathiresan, M.D., told Fierce Biotech that he believes this approach will remedy the side effects. “The safety issues that we're seeing … we think are going to be addressable with [VERVE-102],” he said in an interview. 

The updated lipid nanoparticle for VERVE-102 uses an ionizable lipid and a GalNAc liver-targeting ligand, which diversifies the range of pathways through which the treatment can enter the liver. Fortifying Verve’s confidence is the fact that Intellia Therapeutics licensed the same ionizable lipid from Novartis, which has yet to raise safety concerns with about 75 patients' worth of data.

Verve expects to launch a clinical trial for VERVE-102 in a matter of months, if not weeks, recruiting out of the U.K. and Canada. The first patient is expected to be dosed in the second quarter. It’s a similar strategy as VERVE-101, where the trial began ex-U.S. while the company worked through a preemptive FDA clinical hold. 

Kathiresan underscored that despite the safety concerns among the higher dose group, VERVE-101 seemed to validate the editing technology, exemplified by cholesterol lowering. The first five patients treated with the 0.45-mg/kg dose averaged a 46% drop in low-density lipoprotein cholesterol levels, with the highest reduction reaching 73%. 

“This, to us, suggests that the guide and the editor are working well,” the CEO said.

Kathiresan added that the near-term decision to deprioritize VERVE-101 has no impact on the company's cash runway and should not spur any layoffs.