An emerging class of drugs offers hope in the battle against elevated lipoprotein(a) [Lp(a)], a hereditary condition impacting one in five individuals globally. High Lp(a) levels significantly elevate the risk of premature heart disease, yet many people remain unaware of their condition until a severe event, such as a heart attack or stroke, occurs. Despite its prevalence, testing for Lp(a) is not routinely conducted but is gradually gaining traction. Presently, there is no approved treatment for high Lp(a), but five promising drugs are currently under development.
Muvalaplin, a daily oral medication, demonstrated an impressive reduction in Lp(a) levels by up to 86% in a 12-week phase II study. Unlike other drugs targeting Lp(a), which typically silence genetic instructions from the LPA gene, Muvalaplin operates externally as a small molecule. This distinction underscores its potential as a groundbreaking therapeutic option.
Zerlasiran, an injectable treatment, has shown to decrease Lp(a) levels by nearly 86% in a phase II trial. Similarly, Lepodisiran exhibited sustained Lp(a) reduction of 94% over a year in a phase I trial. Meanwhile, Pelacarsen and Olpasiran—both injectable drugs—achieved reductions in Lp(a) levels by up to 80% and more than 95% respectively, highlighting their potential efficacy.
Despite these promising developments, the results of ongoing clinical trials are about five years away. The first trial is anticipated to conclude by May 2025. As noted by Stephen Nicholls, MBBS, PhD, “So, I think a lot of us are pretty confident with all the information that we've got about Lp(a) that lowering Lp(a) should be beneficial for patients, but the only way to know is to do these large clinical trials.”
The National Lipid Association recommends that individuals undergo at least one Lp(a) test in their lifetime. An estimated 64 million people in the United States face heightened risks of premature heart disease due to elevated Lp(a). However, as Bernadette McLaughlin points out, “We're used to having a fix for things, and there is no fix for this yet.” Despite this, she remains optimistic: “But I will say that it helps me a lot when I read all of the information about what is coming down in the pipeline. It does give you hope.”
Testing for Lp(a) is not part of a standard lipid panel but is considered crucial for early detection and management. Bernadette McLaughlin urges individuals to be proactive: “I strongly suggest that everyone ask their doctor for this very simple blood test.”
The differences between these emerging treatments may not be critically significant according to Steven E. Nissen, MD, who remarked that “the differences may not be all that important.” Yet, Dinesh Kalra, MD, MBA, highlights patient preference as an essential factor: “Some people like to take an injectable every four or six months.”
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