A One-Time Therapy Could Permanently Regulate Cholesterol Levels

(SeaPRwire) –   Heart disease remains the leading cause of death globally. Although physicians prescribe cholesterol-lowering medications and lifestyle modifications to manage major risk factors, adhering to these changes is often challenging for individuals.

Researchers published encouraging findings in the *New England Journal of Medicine* on May 25 regarding a potential one-time gene therapy that could manage cholesterol, a primary driver of heart disease. Conducted by Verve Therapeutics (owned by Eli Lilly Co.), the study involved 35 participants, with the therapy lowering LDL cholesterol by 9% to 62%, depending on the dosage administered.

The therapy targets the PCSK9 gene. Approximately two decades ago, researchers at UT Southwestern Medical Center discovered that individuals with mutations in this gene typically exhibit very low LDL levels and a reduced risk of heart events. PCSK9 regulates cholesterol in the liver, and these individuals possessed an inactive gene variant that lowered blood cholesterol without other apparent side effects. Scientists subsequently developed drugs to inhibit this gene; four such drugs are currently approved. However, as injectable medications, they suffer from compliance issues, with 30-50% of patients discontinuing use within a year, a rate comparable to daily statin pills.

Named VERVE-102, this gene therapy aims to solve compliance issues through a single treatment that edits liver cells to continuously produce an inactive version of PCSK9. While the genetic alteration differs slightly from the naturally occurring mutation, the outcome is identical: the gene is inactivated, resulting in lowered LDL.

“This study provides early clinical evidence that we can confer protection to those not born with it,” stated Dr. Sek Kathiresan, Verve’s vice president of obesity research and CEO. “We still have much to learn. However, if successful, it could represent a novel method for treating high cholesterol with a single infusion for life-long reduction.”

If approved, the gene therapy could replace regular injections or daily pills because the targeted liver cells regenerate every 200 to 300 days. Once edited by VERVE-102, these cells produce new cells with the same genetic change, sustaining the effect of the altered PCSK9—potentially for a lifetime. Patients in the study have been monitored for about 18 months and continue to show low LDL levels. Animal studies indicate the effect persists for at least three years, giving scientists confidence in the treatment’s durability.

The only notable side effect is a temporary elevation in liver enzyme levels, a result of the therapy targeting liver cells and potentially disrupting their compound balance initially.

The current trial included individuals with a genetic predisposition to high cholesterol or those who had experienced early heart events. Lilly plans to conduct a larger trial involving approximately 200 people, including more participants from the latter group to better represent the general heart disease population. The company will also continue to track the 35 participants from the initial trial for 15 years to monitor safety.

For safety reasons, participants in the current study continued taking cholesterol-lowering medications, including statins. Future research will determine if a one-time gene therapy like VERVE-102 could eventually replace statins entirely. “It is too early to say definitively, and much will depend on the patient’s starting cholesterol levels and treatment goals,” said Kathiresan. “Ultimately, our goal is to position this as the preferred therapy of choice.”