Verve's momentum slows as high cholesterol gene editing therapy placed on hold by FDA

Verve Therapeutics’ lead gene editing candidate has lost some steam after running into an FDA clinical hold.

Phase 1 efforts for VERVE-101 in the heart-1 trial of patients with a type of genetic high cholesterol are now on hold, according to the company’s third-quarter earnings report issued Monday. Verve did not disclose the nature of the FDA’s concern but said a notification of the hold was received Friday, Nov. 4. The agency is expected to provide additional details within 30 days.

VERVE-101 is designed to turn off the PCSK9 gene in the liver to lower low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolemia (HeFH), which is a type of atherosclerotic cardiovascular disease. The gene editing therapy differs from CRISPR therapies in that it does not cut DNA but rather amends one base, or letter, in the genome to a different one to effect change.

People with HeFH have a gene mutation in the liver that causes very high cholesterol levels and leads to heart attacks or strokes relatively early in life.

The company filed with the FDA to begin human testing in October. Once the letter from the FDA with details of the hold is received, Verve has pledged to work swiftly to resolve the issue.

Meanwhile, work on the heart-1 trial is underway in New Zealand and the U.K., where dosing has been completed in the initial dose-escalation portion of the study. This initial dose was well tolerated in the three patients, with no treatment-adverse events reported, although there were grade 1 adverse events observed, according to Verve. The company did not disclose the nature of those adverse events.

The trial’s independent data safety monitoring board has recommended dose escalation to the second dose level, which Verve said will begin soon. Initial data are expected to be presented at a medical meeting in the second half of 2023.

Verve reported cash, cash equivalents and marketable securities of $550.7 million as of Sept. 30, enough to ride things out into the second half of 2025. This compares to $360.4 million that was on hand at the end of 2021 and is thanks to a $60 million received from Vertex through a partnership and $247.5 million in net proceeds from the issuance of common stock in the quarter.

The company is also prepping to request clearance for human testing of VERVE-201, a gene editing therapy for another genetically  driven high cholesterol condition called homozygous familial hypercholesterolemia.

Verve's stock was down almost 25% to $23.74 per share in premarket trading Monday, from a closing price Friday of $31.29.