One dose of an experimental drug from Eli Lilly & Co. cut by 94 percent a risk factor that signals heart disease for nearly a year, a first-in-human study found.
Lepodisiran, provided at the highest dose, eased a form of lipoprotein that has been linked to clogged arteries to undetectable levels for 48 weeks.
The analysis, presented on Sunday at an American Heart Association meeting in Philadelphia, boosts the hope that an annual vaccine-like shot could eliminate so-called Lp(a) in people whose genes put them at high risk, said Steve Nissen, a cardiologist at the Cleveland Clinic in Ohio, who led the study.
More than 1 billion people have Lp(a) levels which puts them at moderate-to-high risk of cardiovascular disease, the world’s leading cause of death.
Exercise and diet do bit to decrease levels, and neither do existing drugs, like Lipitor. Cholesterol carried on Lp(a) in the blood can make up vessel walls, forming plaques that decrease blood flow to the heart, brain, and other parts of the body.
These risky deposits can suddenly rupture, causing blockages and leading to heart attacks or strokes.
Nissen said in a statement, “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.”
Lepodisiran is one of several therapeutics in development targeting Lp(a). Olpasiran, which is being developed by Amgen Inc., also showed durable effects in a mid-stage study presented in August. The medications use small interfering RNA to inhibit the production of a key protein component of Lp(a) in the liver.
In the Lilly-sponsored trial, 48 participants were randomized to obtain a placebo or lepodisiran at six different doses. All were given a single, subcutaneous injection in the tummy, apart from the highest dose of 608 milligrams, which was administered as two injections. The outcomes were published in the Journal of the American Medical Association.
Blood levels of the medication increased quickly and returned to baseline within two days, probably because it was transported quickly out of the bloodstream and into the liver. At the highest dose, blood levels of Lp(a) fell rapidly and were undetectable by day 29, remaining unmeasurable from days 29 to 281. They then increased slightly, with a median reduction of Lp(a) levels at 94 percent below baseline at 48 weeks.
The analysis was aimed at testing the protection and tolerability of lepodisiran. A mid-stage trial underway will investigate its effects in people with both high Lp(a) levels and a high risk of early heart attack or stroke.
Lp(a) is not often measured because there are no treatments currently available.
Nissen said, “For now, if you have a strong family history of early heart disease, you should insist on having your Lp(a) measured. As these therapies become available, you can seek treatment. In the meantime, you can take steps to lower your blood pressure, treat high LDL cholesterol if you have it, eat well, and do other things to protect yourself.”
