Muvalaplin shows promise in lowering Lp(a) levels in clinical trial

There are several injectable medications undergoing clinical evaluation as treatments to lower Lp(a) levels. However, none have yet been approved by the U.S. Food and Drug Administration.

Stephen Nicholls, MBBS, Ph.D., study author, director of the Victorian Heart Institute at Monash University in Melbourne, AustraliaMost medications being developed to lower Lp(a) are injectable. Muvalaplin is the first oral agent being developed to lower Lp(a) levels and acts by disrupting formation of the Lp(a) particle."

At week 12, the study found:

• Compared to placebo, muvalaplin treatment reduced Lp(a) by up to 70% as measured by the traditional blood test, and by up to 85.5% as measured by the new intact Lp(a) particle test. Participants who received either 60 or 240 mg of muvalaplin had similar reductions in Lp(a) levels, both of which were greater than the reductions in Lp(a) levels of participants who received 10 mg of muvalaplin.
• Muvalaplin treatment resulted in approximately 97% of participants achieving Lp(a) lower than 125 nmol/L, as measured by the intact Lp(a) particle test, or approximately 82% of participants as measured with the traditional blood test.
• Compared to placebo, muvalaplin lowered apoB, one of two major proteins that make up Lp(a), by as much as 16%, with no notable change in levels of high-sensitivity C-reactive Protein (hsCRP), which is a way to measure heart attack and stroke risk.

"We were encouraged by the degree of Lp(a)-lowering in these patients who are most likely to benefit from its use and by the safety and tolerability," Nicholls said. "While muvalaplin appears to be an effective approach to lowering Lp(a) levels, we still need to study whether Lp(a) lowering will result in fewer heart attacks and strokes."

The study had limitations, including that it was relatively small and trial participants were treated for only 12 weeks. "Larger, more diverse and longer-term studies are needed," Nicholls noted.

Study details, background and design:

• The study included 233 adults with high Lp(a) levels, defined as greater than 175 nmol/L, and either atherosclerotic cardiovascular disease, Type 2 diabetes or familial hypercholesterolemia. 33% of participants were women and 67% were men. 66% self-identified as white adults; 27% as Asian adults; 4% as Black adults; and 3% identified as adults of "other" race.
• The KRAKEN phase II clinical trial was conducted at 43 sites in Asia, Europe, Australia, Brazil and the U.S., from December 2022 to June 2024.
• Participants had clinical visits at study enrollment (baseline) and weeks 1, 2, 4, 8 and 12 during the treatment period. The clinic visits consisted of blood tests for Lp(a) analysis, measurement of a standard lipid profile, and recording of safety and tolerability.

Source:

American Heart Association