Subscriber Benefit
As a subscriber you can listen to articles at work, in the car, or while you work out. Subscribe NowA single dose of Eli Lilly and Co.’s experimental drug cut a risk factor that signals heart disease by 94% for almost a year, a first-in-human study found.
Lilly’s lepodisiran, given at the highest dose, reduced a heart disease-linked protein to undetectable levels for 48 weeks. The research raises hopes that an annual vaccine-like shot could eliminate lipoprotein (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 worldwide have Lp(a) levels that put them at moderate-to-high risk of heart disease. Exercise and diet do little to reduce levels, and neither do existing drugs. The findings, presented Sunday at an American Heart Association meeting in Philadelphia, suggest yet another way of addressing heart disease, the world’s leading cause of death.
“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,” Nissen said in a statement.
Lilly shares fell as much as 3.3% Monday at the opening bell as investors assessed the rapidly evolving potential marketplace for the new class of obesity treatments, but were up 2.5% by midday, to 612.81 each.
At the same meeting, Novo Nordisk A/S unveiled a study showing heart benefits from its weight-loss drug Wegovy, a rival to Lilly’s newly approved Zepbound.
Dangerous deposits
Cholesterol carried on Lp(a) in the blood can build up on vessel walls, decreasing flow to the heart, brain and other parts of the body. These dangerous deposits can suddenly rupture, leading to clots that can cause heart attacks or strokes.
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 gene-blocking technology, called small interfering RNA, to stop the liver from making a component of Lp(a).
In the Lilly-sponsored trial, 48 participants were randomized to receive placebo or lepodisiran at six different doses. All were given a single, sub-cutaneous injection in the tummy, apart from the highest dose of 608 milligrams, which was administered as two injections. The results were also published in the Journal of the American Medical Association.
Blood levels of the medication rose quickly and returned to baseline within two days, likely because it was transported quickly out of the bloodstream and into the liver. At the highest dose, blood levels of Lp(a) declined rapidly and were undetectable by day 29, remaining unmeasurable from days 29 to 281. They then rose slightly, with a median reduction of Lp(a) levels at 94% below baseline at 48 weeks.
Testing recommended
The study was aimed at testing the safety 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.
Patients’ Lp(a) levels are not frequently tested because there are no approved treatments.
“For now, if you have a strong family history of early heart disease, you should insist on having your Lp(a) measured,” Nissen said. “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.”
Please enable JavaScript to view this content.