Muvalaplin Effectively Lowers Lipoprotein(a) in Cardiovascular Patients
|
Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on April 25th, 2025
|
Lipoprotein(a) is critical for packaging and transporting cholesterol in the bloodstream via low-density lipoproteins. Elevated levels of lipoprotein(a) heighten the risk of atherosclerotic cardiovascular disease by promoting plaque buildup. With funding from Eli Lilly, a study was undertaken to evaluate the efficacy of Muvalaplin in controlling lipoprotein(a) levels.
This phase 2 international clinical trial enrolled 233 participants with a median age of 65 years who had serum lipoprotein(a) concentrations of 175 nmol/L or higher and a history of cardiovascular disease. Approximately 70% of the participants had been diagnosed with coronary artery disease, and 40% had experienced a myocardial infarction. Nearly 90% were on statin therapy for cholesterol management, with 40% also using ezetimibe, while antithrombotic agents and beta-blockers were used by about 85% and 50% of the patients, respectively.
Participants were randomly assigned to receive either a placebo or oral Muvalaplin at one of three dose levels (10, 60, or 240 mg). Unlike other therapeutic agents, such as small interfering RNAs that work by suppressing apolipoprotein expression, Muvalaplin uniquely prevents the assembly of lipoprotein(a) by interrupting the disulfide bond between apolipoprotein(a) and apolipoprotein B.
After 12 weeks of treatment, researchers observed that treatment with 240 mg and 60 mg of Muvalaplin reduced lipoprotein(a) levels by 85.8% and 81.7%, respectively - significantly more effective than the unchanged levels seen in the placebo group. However, Muvalaplin did not lower C-reactive protein levels. The frequency of adverse events was similar across the three Muvalaplin dosages and the placebo group. These promising findings support proceeding to a subsequent phase 3 trial involving a larger population and a longer treatment and follow-up period.
This phase 2 international clinical trial enrolled 233 participants with a median age of 65 years who had serum lipoprotein(a) concentrations of 175 nmol/L or higher and a history of cardiovascular disease. Approximately 70% of the participants had been diagnosed with coronary artery disease, and 40% had experienced a myocardial infarction. Nearly 90% were on statin therapy for cholesterol management, with 40% also using ezetimibe, while antithrombotic agents and beta-blockers were used by about 85% and 50% of the patients, respectively.
Participants were randomly assigned to receive either a placebo or oral Muvalaplin at one of three dose levels (10, 60, or 240 mg). Unlike other therapeutic agents, such as small interfering RNAs that work by suppressing apolipoprotein expression, Muvalaplin uniquely prevents the assembly of lipoprotein(a) by interrupting the disulfide bond between apolipoprotein(a) and apolipoprotein B.
After 12 weeks of treatment, researchers observed that treatment with 240 mg and 60 mg of Muvalaplin reduced lipoprotein(a) levels by 85.8% and 81.7%, respectively - significantly more effective than the unchanged levels seen in the placebo group. However, Muvalaplin did not lower C-reactive protein levels. The frequency of adverse events was similar across the three Muvalaplin dosages and the placebo group. These promising findings support proceeding to a subsequent phase 3 trial involving a larger population and a longer treatment and follow-up period.