6 Sept 2023 • About 20–25% of people have high amounts of lipoprotein(a) or Lp(a), which is a genetic variant of low-density lipoprotein (LDL), otherwise known as the "bad" cholesterol. Since Lp(a) is genetic, lifestyle modifications like diet and exercise that may be helpful for other forms of cholesterol are ineffective. Currently, there is no cure or approved specific treatment for lowering Lp(a) levels.

Researchers from Monash University’s Victorian Heart Institute and Victorian Heart Hospital in Australia, conducted a clinical trial to assess an experimental medication for lowering Lp(a) levels called muvalaplin. Muvalaplin essentially blocks the binding of LDL particles to the protein Apo(a) in the liver required for the formation of Lp(a). It would provide an oral option for the treatment of patients with high Lp(a) levels, lowering their risk of heart disease.

This first-in-human phase 1 study involved healthy participants who received muvalaplin orally as single ascending doses ranging from 1 mg to 800 mg and as multiple ascending doses ranging from 30 mg to 800 mg for 14 days.

• Muvalaplin lowered Lp(a) plasma levels within 24 hours after the first dose, with further Lp(a) reduction on repeated dosing.
• Maximum placebo-adjusted Lp(a) reduction was 63% to 65%.
• It was not associated with tolerability concerns or clinically significant adverse effects

Even though these findings may be considered a breakthrough in lowering Lp(a) levels, larger trials are required to further assess the safety, tolerability, and impact of muvalaplin on overall cardiovascular health.

Currently, the only FDA approved therapy for lowering Lp(a) is lipoprotein aphaeresis which physically removes lipoproteins from the blood and is only available for people with certain Lp(a) levels and other risk factors.

Source: JAMA | Read full story