Experimental drug lepodisiran cuts heart disease risk factor by 94%

A single dose of an experimental drug has been found to reduce the risk of genetic heart disease by 94%. Lepodisiran, an experimental drug developed by Eli Lilly, has shown promising results in reducing levels of lipoprotein(a), or Lp(a), a genetically inherited particle linked to an increased risk of heart attacks and strokes. This protein lurks in the body undetected by routine tests and undeterred by existing medications, diet, or exercise.
Lp(a) is a deadly form of cholesterol that has some characteristics in common with LDL cholesterol (low-density lipoprotein cholesterol, also known as “bad cholesterol”), including causing plaque to build up in arteries and reduce blood flow to the heart, brain, kidneys, legs and other parts of the body. A high level of Lp(a) is inherited from your family and is a common independent risk factor for cardiovascular disease, according to the .

According to data presented at a major medical meeting on Sunday, a midstage trial involving the drug lepodisiran, showed promise in reducing Lp(a), by an average of 93.9% versus placebo over six months after one or two 400 milligram doses. For participants receiving a second dose at six months, the reduction reached 94.8% at the one-year mark. No serious adverse events related to the drug were reported. With the second phase showing remarkable success, Lilly will be stepping into phase 3, and the patient enrollment in that trial should be completed this year. The company is also testing muvalaplin, the only oral Lp(a) treatment in clinical trials.

High level of Lp(a) affects an estimated 1.4 billion people globally, including 64 million in the U.S., with individuals of African ancestry at particularly high risk. The experimental drug if confirmed safe for use, could become a crucial tool in treating the millions of Americans genetically predisposed to abnormally high levels of lipoprotein(a), or Lp(a).

The findings from the earlier trial of this drug showed it was safe, however, further trials were required to confirm it. “If further trials show that this medication - lepodisiran - is safe and can reduce heart attacks and strokes, it would be good news for patients because it eliminates a risk factor we’ve been unable to treat,” the lead study author Steve Nissen, M.D., chief academic officer at the Heart, Vascular & Thoracic Institute at the Cleveland Clinic in Ohio earlier said in a statement. “This medication could be a once-a-year injection similar to a vaccine for people with high Lp(a) levels.”

The experimental drug, lepodisiran is a small interfering RNA (siRNA), which disables the messenger RNA that is involved in producing apolipoprotein(a), a key component in the Lp(a) particle. This way it reduces the production of Lp (a).

“How do you beat a risk factor that’s largely genetic? One highly effective approach is to interfere with the gene, and that’s what lepodisiran and other new therapies are designed to do,” Nissen said in 2023.