New Line of Cholesterol Drugs Are On Horizon

 

 

“A new class of drugs is poised to take on an insidious cause of heart attacks and strokes that has eluded treatment.

 

Researchers could know as soon as this summer whether the most advanced experimental drug, from Novartis and its partner Ionis Pharmaceuticals, cuts heart attacks, strokes and deaths in a study that could be used to get their drug approved by next year.

 

Amgen and Eli Lilly are also developing medicines that lower the level of a fatty particle in the blood called lipoprotein(a), or Lp(a) [1]. It can cause plaque to build up in blood vessels and is linked to heart disease. Tens of millions of people in the U.S. have elevated Lp(a), a largely hidden driver of heart disease.

 

If Lp(a) drugs work, companies could be on the verge of the next big heart-drug market. Citi analysts estimate it could be valued at as much as $25 billion a year worldwide.

 

This isn't a sure bet, though. Effective Lp(a) drugs have been difficult to develop. In the past, scientists found drugs that lowered levels of the particle a moderate amount but failed to reduce heart attacks and strokes in research studies, leaving patients with no approved treatment.

 

"It's just been the riddle that nobody could solve," said Monica Florio, who has helped lead research on Amgen's candidate. "Now I think these trials are going to bring us an answer."

 

The Lp(a) particle is a variant of LDL, the so-called bad cholesterol. Like its cousin, high levels of buildup in arteries threaten heart attacks and strokes.

 

Research has failed to prove that lowering a person's Lp(a) will reduce their risk of heart attacks and strokes. For Lp(a) drugs to work, scientists say they must significantly lower overall levels of the particle in the body.

 

Diet and exercise don't lower Lp(a). About 90% of a person's level is fixed at birth. Doctors usually prescribe other cholesterol treatments, such as statins, to manage overall cardiovascular risk -- yet statins can raise Lp(a) levels.

 

Roughly 1 in 5 people globally have dangerously high levels of Lp(a), said Dr. Steven Nissen, a cardiologist at the Cleveland Clinic who is involved in trials to test several of the drugs in development. Lp(a) hardens arteries and promotes clotting, which is "why it is so noxious in terms of increasing adverse cardiovascular events," he added.

 

Drugmakers are now using new technologies to attack Lp(a). Both Amgen's experimental Lp(a) drug and Lilly's deploy a gene-based technology that aims to silence the gene that produces Lp(a).

 

Amgen's trial is expected to have results next year, while Lilly's late-stage trial results aren't expected until 2029.” [2]

 

1. What is the function of lipoprotein(a)?

 

Lipoprotein(a)—commonly referred to as Lp(a)—does not have a single, definitively established physiological function in the human body, but it primarily acts to transport cholesterol and is believed to play a role in wound healing and tissue repair.

Understanding its dual nature helps make sense of how it functions in the body:

1. Physiological Functions (The "Good")

Because humans, primates, and a few other species retained the gene for Lp(a) through evolution, researchers hypothesize it serves beneficial purposes, though individuals born with extremely low levels rarely suffer adverse developmental or immune effects. Its proposed functions include:

•     Transporting Lipids: Like standard LDL cholesterol, it carries fats through the bloodstream to cells.

•     Wound Healing & Clotting: Its unique protein structure (called apolipoprotein(a)) mimics key clotting factors in the blood. It helps carry cholesterol to sites of injury, playing a potential role in repairing damaged blood vessels and tissues.

•     Scavenging: It acts as a primary carrier and "sink" for oxidized phospholipids in the circulation, helping to clear out potentially harmful damaged lipids.

2. Clinical Significance & Risks (The "Bad")

 

While Lp(a) likely evolved for injury repair, in the context of modern cardiovascular health, it often works against the body.

 

 High levels of Lp(a) are strongly associated with a higher risk of heart attack, stroke, and aortic valve disease. It operates as a cardiovascular threat in three main ways:

•           Plaque Formation: Like LDL cholesterol, Lp(a) builds up in artery walls, contributing to blockages.

•           Increased Clotting: Because it resembles a clot-promoting protein (plasminogen), it can inhibit the body's ability to break down blood clots, leading to rapid blockages in blood vessels.

•           Inflammation: It carries highly inflammatory oxidized phospholipids, which can cause plaques to rupture or trigger calcium buildup in the aortic valve.

 

2. U.S. News: New Line of Cholesterol Drugs Are On Horizon. Martinez, Xavier.  Wall Street Journal, Eastern edition; New York, N.Y.. 28 May 2026: A3.