About 20-25% of people worldwide have a genetic version of “bad” cholesterol called lipoprotein(a), or Lp(a) for short. There is currently no specific approved cure or treatment to lower Lp(a) levels. Between 20 and 25% of people worldwide have elevated levels of lipoprotein(a), more commonly known as Lp(a), a genetic form of LDL cholesterol, also known as “bad” cholesterol. Because Lp(a) is genetic, lifestyle changes (e.g. diet and exercise) that can benefit other types of cholesterol do not help. There is currently no specific approved cure or treatment to lower Lp(a) levels. Now, researchers at Monash University have discovered an experimental oral drug that was able to lower Lp(a) levels during a first-in-human Phase 1 clinical trial.
This molecule developed to target Lp(a) can lower its levels by up to 65%. Lp(a) is a form of LDL cholesterol that is “stickier” than other types, making it easier to build up and block arteries. The amount of Lp(a) in a person’s system is determined by their genetic history and ethnicity. Having a high Lp(a) level can increase a person’s risk of cardiovascular diseases such as coronary heart disease and stroke. Lp(a) is formed when an LDL particle binds to the protein Apo(a). Muvalapline essentially blocks the binding that takes place in the liver and thus prevents the formation of Lp(a). It would provide an oral option for treating patients with elevated Lp(a) levels to reduce the risk of heart disease.
For this phase 1 clinical study, Dr. Nicholls and his team recruited 114 healthy participants of various genders and ethnic backgrounds. The purpose of this study was to evaluate the safety and tolerability of muvalaplin, its pharmacokinetics, as well as indicators of the drug’s effect on its target, Lp(a). Participants received a single dose of muvalapline, an escalating dose in which the amount taken was increased over time, or a placebo for 14 days. At the end of the study, researchers found that participants who received muvalapline lowered their Lp(a) levels by up to 65%. In terms of safety and tolerability in humans, muvalaplin was not associated with any tolerability issues or clinically significant adverse effects.
The side effects most commonly reported by study participants included headache, back pain, fatigue, diarrhea, abdominal pain and nausea. Several expert cardiologists not involved in Dr. Nichols’ research agree on the potential of this drug in the management of genetic hypercholesterolemia. Lp(a) is a recognized but often little-considered cardiac risk factor and could be responsible for fatal cardiac events that occur in young people. That’s why experts believe muvaliplin could be a new “gamechanger” in the treatment of high cholesterol. This study was recently published in the journal JAMA.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Scientific references
Nicholls SJ et al. JAMA 2023 Aug 28:e2316503.
Zhang J et al. Am J Cardiovasc Drugs. 2023 Sep 6.
Nielsen ST et al. Eur Heart J. 2023 Aug 26:ehad547.