Advances in lipid therapeutics were the focus of a late-breaking science session at AHA 2024, with researchers presenting findings evaluating the safety of the novel new drug muvalaplin in lowering high levels of lipoprotein(a) [Lp(a)], as well as looking at obicetrapib as an adjunct to maximally tolerated lipid-modifying therapies in patients with heterozygous familial hypercholesterolemia (HeFH).

Muvalaplin, a novel small molecule inhibitor taken orally, safely and effectively lowered high levels of Lp(a), based on findings from the KRAKEN study, simultaneously published in JAMA, which 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 from 43 sites in Asia, Europe, Australia, Brazil and the U.S.

Researchers evaluated the effects of muvalaplin at different doses – 10 mg, 60 mg or 240 mg, taken daily – compared with a daily placebo for 12 weeks. Lp(a) levels were tested using both the traditional Lp(a) blood test and a new test that more specifically measures the levels of intact Lp(a) particles in the blood.

At 12 weeks, results showed that 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. Approximately 97% of participants in the muvalaplin group achieved 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.

"Most 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," said study author Stephen Nicholls, MBBS, PhD, FACC. "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. 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."

In the BROOKLYN trial, researchers said obicetrapib produced significant LDL-C lowering at day 84 with sustained effect through one year in patients with HeFH. The trial randomized 354 patients with HeFH and fasting LDL-C >=70 mg/dL and who were taking maximally tolerated lipid-modifying therapies to receive obicetrapib (10 mg) or matching placebo orally daily for 52 weeks in a 2:1 ratio.

In presenting the findings, Nicholls, noted that "obicetrapib holds promise for patients with HeFH who are unable to attain their LDL-C treatment targets with available lipid-lowering agents."