First in Human Long-Acting Gene Silencing Therapy Significantly Lowers Heart Disease Risk Marker with One Injection

Findings from a Phase 1 clinical trial led by Cleveland Clinic show a single injection of Kylo-11 produced reductions in lipoprotein(a) levels, with the highest doses reducing levels by approximately 95–97% and maintained the reductions for 48 weeks. 

Lipoprotein(a) is a key driver of heart disease and stroke that is typically considered an untreatable risk factor.

Findings were presented today during a late-breaking science session at the European Society of Cardiology’s annual meeting in Munich and simultaneously published in the Lancet.

Lipoprotein(a), commonly known as Lp(a), is a cholesterol-carrying particle produced primarily in the liver. It shares similarities with low-density lipoprotein (LDL), often referred to as “bad cholesterol,” but is largely controlled by genetics rather than lifestyle. In fact, about 80–90% of a person’s Lp(a) level is inherited. Because of its unique structure, elevated Lp(a) can contribute to the buildup of plaque in artery walls and increase the tendency for blood clots, raising the risk of heart attack and stroke.

While treatments that lower LDL cholesterol and other blood fats have significantly improved cardiovascular health, there are no approved medications specifically designed to lower Lp(a). Unlike LDL cholesterol, Lp(a) levels are not meaningfully reduced through diet, exercise or other lifestyle changes.

The first-in-human, double blind, randomized trial enrolled 71 people in China, with 70 receiving a single injection of Kylo-11 or placebo and being followed for about 11 months. Kylo-11 uses a technology called small interfering RNAor siRNA and works by delivering a genetic “silencing” signal to liver cells, since the liver is where Lp(a) is produced. That signal then reduces production of apolipoprotein(a) or apo(a), a key building block of Lp(a). With less apo(a) being made, the body produces much less Lp(a). Results across the dosing groups showed a single injection reduced Lp(a) concentrations by approximately 53% to 97% at 48 weeks. Participants receiving the highest doses experienced reductions of about 95–97%, with the effect sustained for nearly one year.

“Most people with high Lp(a) don’t know it,” said lead author  Ashish Sarraju, M.D., a cardiologist in the Heart, Vascular & Thoracic Institute  at Cleveland Clinic.

“Despite its significant impact on cardiovascular risk, Lp(a) is still underrecognized and undertested,” said Dr. Sarraju. “Improving awareness and routine testing will be critical as promising new therapies like this one emerge to potentially address this unmet need.”

A Phase 2 trial is underway by the sponsor of the Phase 1 trial, Kylonova Biopharma, in collaboration with Dr. Sarraju and Cleveland Clinic. Kylonova Biopharma is a subsidiary of Hygieia Pharma, an SBP GROUP company.