Clinical testing of Verve Therapeutics’ genetic drug targeting an inherited form of high cholesterol continues in the UK and New Zealand, but plans for a US clinical trial hit a regulatory speed bump after the FDA delayed a new application of the biotech drug.
Verve announced FDA clinical hold for its gene therapy, VERVE-101, in connection with the launch of financial results for the third quarter of 2022 on Monday. The Cambridge, Mass.-based company did not provide details about the hold, other than to say that the hold on the FDA notice came last Friday and a formal letter outlining the agency’s issues is expected within 30 days.
“Verve plans to provide updates pending engagement with the FDA and intends to work closely with the FDA to resolve the hold as quickly as possible to begin dosing in the US,” the company said in a statement.
VERVE-101 is designed to turn off the PCSK9 gene, which produces a liver protein that makes it harder for the body to clear low-density lipoprotein (LDL), the “bad” form of cholesterol. High amounts of this type of cholesterol increase the risk of heart disease and stroke. Antibody drugs are available from Amgen and Regeneron Pharmaceuticals to block PCSK9 and Novartis won FDA approval last year for Leqvio, a drug that stops the gene from making the protein. But all three drugs must be dosed periodically. Verve’s gene therapy aims to turn off the gene permanently, offering the potential for a one-time treatment.
The first indication for Verve gene therapy is heterozygous familial hypercholesterolemia (HeFH). People born with this disease have high cholesterol levels that cannot be reduced with diet and exercise alone. In monkey studies, Verve reported an 89% reduction in PCSK9 protein levels, along with an average 59% reduction in cholesterol levels two weeks after dosing. This reduction was maintained for 15 months after treatment.
In the summer, a patient from New Zealand became the first dose in humans with Verve gene therapy. The company has since been given the green light to proceed with clinical trials in the UK. Verve said on Monday that clinical data from New Zealand and the UK were not part of the filing seeking FDA approval to begin a clinical trial in the US.
In the first group of patients dosed so far, Verve said the therapy was well tolerated and all side effects were classified as low grade. The independent trial data safety monitoring board reviewed the safety data and recommended that testing be escalated to the next dose level. Verve said it expects to report preliminary data from both groups at a medical meeting in the second half of 2023.
In a note sent to investors Monday morning, William Blair analyst Raju Prasad wrote that another genetic drug biotech, Beam Therapeutics, received a clinical hold on its exploratory new drug filing but was able to resolve it in three months, signaling that Verve can expect a similar timeframe. Previous clinical holdups in gene editing have also resulted in resolutions within about three months. Prasad added that the lack of safety issues so far and the continuation of the study to the next dosage level are positives for Verve gene therapy.
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