Imagine receiving a single injection and seeing one of the most stubborn inherited risk factors for heart disease fall by more than 95%, with the effect still visible almost a year later. That is what researchers have reported in an early human trial of an experimental drug called Kylo-11. The findings could open an exciting new chapter in cardiovascular medicine, although much larger studies will be needed to establish whether lowering this marker actually prevents heart attacks and strokes.
Cholesterol has been at the centre of heart disease prevention for decades. Doctors routinely advise patients to monitor their cholesterol, manage blood pressure, exercise and follow a heart-healthy diet.
But there is another cardiovascular risk factor that many people have never heard of.
It is called lipoprotein(a), or Lp(a).
Unlike ordinary LDL cholesterol, Lp(a) levels are largely determined by genetics. Someone can maintain a healthy weight, exercise regularly, eat carefully and still carry dangerously elevated levels.
Now, a research team involving Cleveland Clinic scientists has reported results from a Phase 1 clinical trial of Kylo-11, an experimental RNA-based treatment designed to reduce Lp(a) production in the liver.
The results, published in The Lancet in September 2026, are striking: participants receiving the highest doses experienced reductions of approximately 95–97%, sustained through 48 weeks after a single injection.
It is an encouraging development. But the most important question is no longer simply whether scientists can lower Lp(a). It is whether doing so can meaningfully reduce the risk of cardiovascular disease.
The hidden heart disease risk factor that can run in families
Lp(a) is a cholesterol-carrying particle circulating in the bloodstream. It resembles LDL cholesterol but has an additional protein attached to it, known as apolipoprotein(a).
That additional component makes it particularly interesting to cardiovascular researchers.
Elevated Lp(a) is an established, largely genetically determined risk factor for atherosclerotic cardiovascular disease. It is also associated with aortic valve stenosis, a condition in which the valve controlling blood flow out of the heart becomes narrowed.
The danger is that many people with elevated Lp(a) have no obvious symptoms.
They may discover their levels are high only after a cardiovascular assessment or, sometimes, following a heart attack in the family.
Research suggests that approximately one in five people worldwide has elevated Lp(a), although the prevalence varies between populations.
The American Heart Association’s scientific statement on Lp(a) explains why this inherited risk factor deserves greater attention.
Unlike conventional LDL cholesterol, Lp(a) is not meaningfully reduced through diet and exercise. Lifestyle changes remain important for overall cardiovascular health, but they generally cannot correct genetically elevated Lp(a).
That has made it an important target for the next generation of cardiovascular medicines.
What makes Kylo-11 different from conventional cholesterol treatments?
The experimental treatment uses a technology called small interfering RNA, commonly abbreviated as siRNA.
Rather than simply removing cholesterol from the bloodstream, Kylo-11 attempts to reduce the production of Lp(a) at its biological source.
The liver plays a central role in producing this particle. Within liver cells, genetic instructions from the LPA gene help produce apolipoprotein(a), one of its essential building blocks.
Kylo-11 is designed to interfere with those instructions.
Its siRNA molecules target the messenger RNA responsible for producing apolipoprotein(a). By reducing the availability of that messenger RNA, the treatment lowers production of the protein and, consequently, the amount of Lp(a) assembled and released into circulation.
The approach is known as RNA interference.
It is a fascinating example of how modern medicine is moving beyond treating the consequences of disease and towards targeting the molecular instructions that contribute to it.
The researchers describe Kylo-11 as a non-canonical, long-acting siRNA treatment with an unusual molecular design intended to support prolonged activity.
The full clinical findings were published in The Lancet.
The Phase 1 trial: What happened after one injection?
The Kylo-11 research was a randomised, double-blind, placebo-controlled, first-in-human Phase 1 clinical trial conducted at a hospital-based research centre in China.
The study enrolled 71 participants between May and December 2024. Of these, 70 received either Kylo-11 or a placebo.
Participants were divided into different dosage groups, receiving single injections ranging from 9 mg to 600 mg.
Researchers monitored their health and measured changes in blood Lp(a) concentrations.
The results, published in The Lancet, were particularly impressive at the higher doses.
At 48 weeks:
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The 225 mg group experienced a median Lp(a) reduction of approximately 94.6%.
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A separate 225 mg group involving participants with particularly high starting Lp(a) levels experienced a reduction of approximately 95.6%.
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The 450 mg group recorded a reduction of approximately 96.3%.
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The 600 mg group achieved a reduction of approximately 97%.
These were median reductions, not guarantees that every participant experienced exactly the same response.
At the highest dose, the reduction remained close to its maximum even after approximately 11 months.
For the researchers, this was an important finding because many existing RNA-based treatments require repeated administration to maintain their effects.
A treatment capable of producing such prolonged suppression after one injection could potentially reduce the frequency of future dosing.
The trial was led by researchers including Dr Ashish Sarraju and Dr Steven Nissen of Cleveland Clinic.
Read the complete Phase 1 study in The Lancet.
Why the 48-week result is so important
Most medicines work for a limited period. Their effects gradually decline as the body metabolises or eliminates them, meaning patients need additional doses.
Kylo-11 appears to behave differently.
The researchers found that the higher doses produced substantial Lp(a) reductions that persisted through the 48-week follow-up period.
This is especially interesting because the treatment targets the biological production of Lp(a), rather than simply removing existing particles from circulation.
The study suggests that its unusual siRNA design may help extend the duration of gene silencing.
However, scientists still need to establish how long the effect lasts beyond the period examined in this trial.
A once-yearly treatment schedule is a possibility worth investigating, not an established dosing recommendation.
Was the experimental treatment safe?
Reducing a cardiovascular risk marker dramatically is encouraging. But any new injectable medicine must also demonstrate that it can be administered safely.
In the Kylo-11 trial, the safety results were encouraging.
Among the 70 participants who received treatment or placebo, 37 reported adverse events during the first 24 weeks. Most were mild or moderate, and investigators considered the majority unrelated to the study medication.
Importantly, the researchers reported:
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No serious adverse events.
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No injection-site reactions.
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No drug-related adverse events.
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No deaths.
The findings provide an encouraging initial safety signal.
However, there is a major limitation: this was a relatively small Phase 1 study involving otherwise healthy adults, with a median age of just 27.5 years.
It was primarily designed to investigate safety and tolerability, not to establish whether Kylo-11 prevents heart attacks, strokes or cardiovascular deaths.
A treatment that looks safe in 70 participants cannot automatically be considered safe for hundreds of thousands of patients.
Larger trials, involving older people and individuals with established cardiovascular disease, will be essential.
Can lowering Lp(a) actually prevent heart attacks?
This is the question that could ultimately determine whether Kylo-11 becomes an important cardiovascular medicine.
Scientists already have strong evidence that elevated Lp(a) is a causal risk factor for atherosclerotic cardiovascular disease.
But lowering a risk marker and demonstrating fewer cardiovascular events are two different things.
For example, a medicine might reduce Lp(a) by 97%, yet researchers still need to establish whether this translates into fewer heart attacks, strokes and other serious complications.
That requires large cardiovascular outcomes trials involving thousands of participants followed over several years.
Other experimental Lp(a)-lowering treatments are already being investigated, including olpasiran, lepodisiran and pelacarsen.
These programmes are helping researchers determine whether directly targeting Lp(a) can deliver measurable cardiovascular benefits.
The results could influence how cardiologists approach inherited cardiovascular risk in the future.
What happens next for Kylo-11?
The encouraging Phase 1 findings have provided the foundation for further clinical investigation.
According to Cleveland Clinic, a Phase 2 study is underway through the drug’s sponsor, Kylonova Biopharma, to investigate the treatment further.
The next stage will need to answer several important questions:
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Can the dramatic Lp(a) reductions be reproduced in a larger patient population?
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Does the treatment remain effective in people with established cardiovascular disease?
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How long does the effect last beyond 48 weeks?
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What dosage provides the best balance between effectiveness and safety?
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Does reducing Lp(a) actually translate into fewer cardiovascular events over time?
The researchers will also need to examine potential longer-term adverse effects that a small early-stage trial cannot reliably detect.
For the latest research developments, see Cleveland Clinic’s announcement of the Kylo-11 findings.
Why this discovery matters for people who don’t know their Lp(a) levels
One of the biggest challenges with Lp(a) is that people rarely know whether their levels are elevated.
Unlike blood pressure or ordinary cholesterol, Lp(a) is not routinely included in every standard health check.
Because levels are largely inherited and generally remain relatively stable throughout life, many cardiovascular experts recommend measuring Lp(a) at least once in adulthood.
The National Lipid Association’s scientific guidance and the American Heart Association’s resources provide useful information about assessing this risk factor.
For people with a family history of premature heart disease, discussing Lp(a) testing with a healthcare professional may be particularly worthwhile.
Importantly, Kylo-11 is still investigational. It is not an approved treatment, and nobody should stop or change existing cholesterol or cardiovascular medication because of these findings.
Managing blood pressure, LDL cholesterol, diabetes, smoking and other established cardiovascular risks remains essential.
A new direction for cardiovascular medicine
For years, cardiovascular medicine has focused heavily on controlling cholesterol through statins and other lipid-lowering treatments.
Those therapies have transformed heart disease prevention, but they do not adequately address every inherited risk factor.
Kylo-11 represents a different approach: using genetic instructions to reduce the production of a potentially dangerous blood particle.
A single injection producing nearly a 97% reduction in Lp(a) that remains evident 48 weeks later is a remarkable early clinical result.
It is not yet proof that heart attacks can be prevented with one annual injection. That evidence still needs to come from larger and longer studies.
But the direction is promising.
For people who have inherited elevated Lp(a) levels, the possibility of a future treatment that requires only occasional injections could represent a significant change in cardiovascular care.
The next breakthrough in heart disease prevention may not come from lowering another type of cholesterol. It may come from finally addressing a genetic risk factor that, until recently, doctors had very few ways to treat.
