A ground-breaking human trial has shown promising results for an experimental drug called muvalaplin, which has the potential to reduce cholesterol levels that clog blood vessels. The study, funded by pharmaceutical company Eli Lilly, offers hope for finding effective ways to combat a form of lipoprotein that is closely linked to cardiovascular disease, the leading cause of death worldwide.
Understanding the role of lipoproteins
Lipoproteins are a combination of proteins and fats that carry cholesterol around the body through the circulatory system. Cholesterol plays a critical role in a variety of vital functions, including building the cell wall, producing vitamin D, and synthesizing hormones. However, one lipoprotein, lipoprotein(a) or Lp(a), is known to be more “sticky” than others and tends to build up and clog blood vessels. Recent studies have established a link between Lp(a) levels and cardiovascular disease, as well as poor circulation and strokes.
Problems associated with decreased levels of Lp(a)
Lowering Lp(a) levels is notoriously difficult, as dietary changes and increased physical activity often yield minimal results. Previous attempts to lower lipoprotein levels with medications have also proven to be ineffective. Therefore, researchers are now focusing on preventing Lp(a) formation as a new approach.
Muvalaplin is a new oral drug specifically designed to prevent lipoprotein(a) formation. In a randomized, double-blind clinical trial, Dr. Stephen Nicholls and his team at Monash Health evaluated the efficacy of muvalaplin on 114 volunteers, which included people of different gender, race and age ranging from 18 to 69 years old.
Promising study results
In the first phase of the study, 55 healthy participants received a single dose of muvalaplin ranging from 1 mg to 800 mg or a placebo to assess the drug’s safety. Then, 59 healthy participants with plasma Lp(a) levels above normal received placebo, oral doses of 30 mg, or doses up to 800 mg.
As early as 24 hours after the first dose, participants experienced a significant decrease in plasma Lp(a) levels. The degree of reduction varied depending on the dose of the drug, with some patients experiencing reductions as high as 65% throughout the study. Notably, the reduction in Lp(a) levels persisted for 50 days after the last dose of the drug, with muvalaplin having no effect on the levels of other fats. In addition, the drug was well tolerated by all participants.
Safety and side effects
The first phase of clinical trials is primarily aimed at establishing the safety of the new substance for humans. Therefore, possible side effects were carefully monitored throughout the study. A total of 175 side effects were reported, including mild symptoms such as headache, back pain, fatigue, nausea and diarrhea. Importantly, these side effects did not increase in frequency with higher doses and passed without any long-term effects.
Despite the promising results of the first trial, further studies are needed to determine the overall effectiveness of muvalaplin. The drug is currently undergoing a phase II clinical trial with a larger population of subjects, which will allow its efficacy to be evaluated with greater statistical power. Long-term risks will be evaluated over several years.
Dr. Nicholls and his associates conclude that “the initial results of the Phase I clinical trial suggest that muvalaplin effectively reduces Lp(a) levels without serious side effects.” The study offers hope for people suffering from high levels of Lp(a) and may pave the way for new treatments for cardiovascular disease.