Prateek Tanmay
For years, doctors have treated high levels of low-density lipoprotein (LDL) or the heart attack-triggering bad cholesterol as a lifelong condition. They have prescribed daily statins and even expensive injections when LDL has remained stubbornly high, telling patients the regime was not to be ended. Now, a new experimental therapy from US pharma major Eli Lilly and its subsidiary Verve Therapeutics is challenging that assumption with a single shot infusion that may bust LDL at one go.
In an early-stage clinical trial, published in ‘The New England Journal of Medicine’ and presented at the European Atherosclerosis Society Congress this week, researchers reported that a single infusion of a gene-editing therapy called VERVE-102 sharply lowered LDL cholesterol by 62 per cent for as long as 18 months after treatment.
The therapy works by permanently switching off a cholesterol-related gene called PCSK9 inside the liver.
If larger studies confirm the findings, scientists say the treatment could mark the beginning of a radically different era in preventive cardiology: one where some people may no longer need decades of cholesterol medication because the genetic driver of their disease risk has been edited just once. “For India, where heart disease strikes younger and more aggressively than in many Western populations, the implications could be significant if the findings hold in larger trials,” says Dr Balbir Singh, Chairman, Cardiac Sciences, Max Healthcare.
What exactly is VERVE-102?
VERVE-102 is not a traditional drug. It is a form of in vivo (administered directly to the patient’s body) base editing — an advanced genetic technology related to CRISPR, which allows scientists to alter DNA and modify gene function. Instead of temporarily blocking cholesterol production with medicines, researchers use genetic instructions delivered through an intravenous infusion to permanently alter liver cells from producing it altogether.
“The therapy targets a gene called PCSK9, which plays a major role in controlling LDL cholesterol levels in the blood. The PCSK9 gene is the biological instruction manual (DNA) that your body uses to build the PCSK9 protein. The gene holds the code, whereas the protein is the physical, active worker carrying out tasks in your body. Normally, the liver removes LDL cholesterol using LDL receptors. But the PCSK9 protein destroys many of those receptors before they can do their job. The result: more cholesterol stays circulating in the bloodstream, increasing the risk of blocked arteries, heart attacks and strokes. Now, VERVE-102 attempts to solve that problem at its source by turning off the PCSK9 gene itself,” explains Dr Singh.
The biological idea comes from nature. Scientists discovered years ago that some people are born with naturally occurring non-functional variants in the PCSK9 gene. “These individuals had lifelong low cholesterol levels and strikingly lower rates of coronary heart disease. This new therapy attempts to mimic that protective effect artificially,” he adds. Although scientists have tried to find out why this gene exists in the first place, Dr Singh points out how researchers believe it was probably an in-built defence mechanism to protect the human body from starvation and fasting.
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What did the trial actually show?
The Phase 1b Heart-2 trial involved 35 participants with inherited cholesterol disorder or premature coronary artery disease. Participants received a single intravenous infusion of VERVE-102 across six dose levels. At the highest dose, PCSK9 protein levels fell by as much as 88 per cent while LDL cholesterol fell by as much as 62 per cent.
Importantly, the reductions appeared to last. Some participants have now been followed for up to 18 months, and the cholesterol-lowering effects have persisted throughout that period.
Researchers also reported that the therapy was generally well-tolerated. There were no treatment-related serious adverse events and no dose-limiting toxicities in the study so far. Some participants experienced mild infusion reactions and fatigue.
“That matters enormously because an earlier Verve programme had raised liver safety concerns, making this trial rather significant,” says Dr Singh.
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Why are cardiologists excited?
The treatment represents something medicine has never really had before for cardiovascular disease: the possibility of a one-time genetic intervention for lifelong cholesterol reduction.
“Today, many patients with severe cholesterol disorders require daily statins, multiple medications, or repeated PCSK9 antibody injections. I have seen adherence and discipline to be challenges among my patients who give them up midway as their LDL levels come down,” says Dr Singh.
Why does this matter so much for India?
Familial cholesterol, the inherited condition studied in the trial, also remains massively underdiagnosed in India despite affecting an estimated one in every 200 to 250 people globally. This makes the idea of prevention particularly compelling. “If therapies like VERVE-102 eventually become safe, scalable and affordable (gene editing is costly), they could potentially help high-risk individuals before arteries become permanently damaged. But this was a small number and many more trials are needed across wider sample groups for certainty. We need proof that permanently lowering cholesterol through gene editing actually reduces heart attacks, strokes and cardiovascular deaths over many years. But there is proof of concept for the first time,” says Dr Singh.
