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Novel siRNA therapeutic could lower cardiovascular disease risk

A Phase II trial for the small interfering RNA (siRNA) therapeutic lepodisiran is currently underway, assessing its ability to reduce lipoprotein(a) levels.

Lepodisiran - Novel siRNA therapeutic could lower cardiovascular disease riskLepodisiran - Novel siRNA therapeutic could lower cardiovascular disease risk

A single dose of lepodisiran, a small interfering RNA (siRNA) therapeutic, produced over 94 percent reductions in blood levels of lipoprotein(a), also known as Lp(a), with the results lasting for nearly a year, findings from a Phase I trial show.


Lepodisiran is a siRNA therapeutic that blocks the messenger RNA needed to manufacture a key component of lipoprotein(a) in the liver.

Data revealed at the AHA 2023 Scientific Sessions showed that participants who received lepodisiran had lipoprotein(a) levels reduced by the top dose as much as 96 percent within two weeks. These levels were maintained more than 94 percent below baseline for 48 weeks.

Additionally, it was revealed that the siRNA therapeutic enabled maximum Lp(a) plasma concentrations to be reduced by 49 percent from baseline levels for the 4mg dose. These concentrations were lowered by up to 96 percent for the 608mg dose. A five percent decrease was seen individuals given placebo. No safety issues were observed in the trial.

“These results showed that this therapy was well tolerated and produced very long-duration reductions in Lp(a), an important risk factor that leads to heart attack, stroke and aortic stenosis,” commented lead author Dr Steven Nissen, Chief Academic Officer of the Heart, Vascular & Thoracic Institute at Cleveland Clinic.

The data on the siRNA therapeutic were presented at the American Heart Association’s (AHA) Scientific Sessions 2023 and published in the Journal of the American Medical Association

The clinical trial enrolled 48 patients in the US and Singapore with a mean age of 47. Six different injectable dosages and a placebo were investigated.

Reducing the risk of cardiovascular diseases

“Despite the strong evidence of the importance of elevated Lp(a) as a risk factor for heart disease, effective treatment has been elusive,” stated Dr Nissen.

Therefore, the findings from the trial on the siRNA therapeutic suggest that lepodisiran could be an effective treatment for atherosclerotic cardiovascular diseases in individuals with high Lp(a) levels, according to the researchers.

A Phase II trial studying lepodisiran is currently underway. Eli Lilly and Company, the company developing lepodisiran, sponsored the Phase I trial.