Why It's Too Early For Excitement About Lepodisiran's Ability To Reduce Cholesterol By Almost 100 Percent
NBC News touted the recent trial results for "stealthy cholesterol," but it is too early to call this the holy grail for eliminating coronary artery disease.
A new drug trial has touted results showing that Lp(a) was reduced by almost 100 percent. NBC News responded by hyping this new approach to reducing “stealthy cholesterol.” I assumed they named it stealthy because it is not part of routine blood fat tests, and therefore, most people are unaware of their levels. Lp(a) combines fat (cholesterol) and protein into one molecule. Yes, it does carry bad cholesterol throughout the body. Lp(a) is the same thing as lipoprotein (a).
Elevated lipoprotein(a) concentrations are associated with atherosclerotic cardiovascular disease. As is the case of high blood cholesterol, it is also associated with coronary artery disease (CAD) but by itself does not cause it. How much cholesterol, particularly the bad form, contributes to CAD formation and worsening is still debated.
Lepodisiran is a new experimental drug that interferes with RNA in the hepatic (liver) synthesis (formation) of lipoprotein(a). The drug’s true safety and efficacy are still unknown. The above-referenced drug trial randomly assigned 320 patients with high levels of Lp(a) to placebo or Lepodisiran. The Lp(a) blood levels were then determined at 60 and 180 days. Lepodisiran significantly reduced Lp(a) levels by an average of 93.9% over the 60 to 180-day period after treatment with the highest tested dose (400 mg).
More trials will be needed before the drug is approved for elevated levels of Lp(a), a genetically inherited condition that is not modifiable with diet or exercise. However, cautious optimism can be justified.
Reasons For Optimism
Elevated Lp(a) levels affect 20–25% of the population and are known to be an independent risk for CAD. Until now, there have been no known drug treatments for lowering these high levels.
Lepodisiran was well tolerated and is long-acting in this small study.
The study was conducted in North and South America, Europe and Asia, encompassing diverse patient populations.
A new and larger study of 12,500 patients is currently enrolling patients.
Reasons For Caution
Drug approval is at least three years away.
Only two percent of the study population was black, and they are known to have higher levels of Lp(a).
Because the drug is so long-acting, serious side effects may take longer to become apparent.
Most of the 1.4 billion people globally with elevated Lp(a) haven’t yet had a cardiovascular event, so phase 3 trials of these therapies in a primary prevention setting are important.
Because an independent risk factor for CAD can be reduced, this does not mean it will reduce CAD. For example, the body might react to the Lp(a) reduction by having bad cholesterol delivered to the organs by some other mechanism.
More time and trials are necessary to resolve these issues. At this point, we can be cautiously optimistic. However, we are still far from declaring this a “blockbuster drug” or a cure. As far as this type of “cholesterol” being “stealthy,” there are now blood tests that can measure it. I view this as the opening act of a story that will take years to play out.
Dr. David Mokotoff, a retired cardiologist and prolific writer, shares his medical insights on platforms like Medium and Substack. While the specific content of his article "Why it's too early for excitement" isn't available in the provided information, his writings often offer thoughtful perspectives on health and wellness topics.