Lp(a) Reduction: New ASCVD Therapies
- The role of lipoprotein(a) (Lp[a]) as a key indicator of cardiovascular risk is gaining increased attention.At the 2025 National Lipid Association (NLA) Scientific Sessions, Dr.Marlys L.
- Lp(a) is a unique particle similar to LDL cholesterol, bound to apolipoprotein(a), Koschinsky explained.Elevated levels, typically above 50 mg/dL, are largely genetically determined and are a strong, independent...
- Koschinsky outlined two main therapeutic approaches: antisense oligonucleotides (asos) and small interfering RNAs (siRNAs).Both ASOs and siRNAs work by reducing the production of apo(a) in the liver.
New Lp(a) therapies show real promise in reducing cardiovascular risk, a meaningful step forward for patients. Elevated Lp(a) levels, often genetically persistent, are a major independent risk factor for atherosclerotic cardiovascular disease (ASCVD). This in-depth report spotlights emerging treatments, including antisense oligonucleotides (ASOs) adn small interfering RNAs (siRNAs), which actively target and lower Lp(a).Clinical trials like Lp(a)HORIZON, OCEAN(a), and ACCLAIM-Lp(a) are underway, with initial results demonstrating significant reductions, giving new hope to those with high Lp(a) and ASCVD. News Directory 3 stays at the forefront, bringing you updates from leading research. wondering about the impact of these advancements? Discover what’s next in the fight against heart disease.
Lp(a) Therapies Show Promise in Reducing Cardiovascular risk
Updated May 31, 2025
The role of lipoprotein(a) (Lp[a]) as a key indicator of cardiovascular risk is gaining increased attention.At the 2025 National Lipid Association (NLA) Scientific Sessions, Dr.Marlys L. Koschinsky discussed the latest advancements in Lp(a)-targeted therapies. Koschinsky, a professor at the University of Western Ontario, highlighted the underlying mechanisms of Lp(a) as a cardiovascular risk factor and reviewed current and upcoming treatments.
Lp(a) is a unique particle similar to LDL cholesterol, bound to apolipoprotein(a), Koschinsky explained.Elevated levels, typically above 50 mg/dL, are largely genetically determined and are a strong, independent risk factor for atherosclerotic cardiovascular disease (ASCVD), including heart attack and stroke. Traditional cholesterol-lowering drugs have limited impact on Lp(a),underscoring the need for targeted therapies.
Koschinsky outlined two main therapeutic approaches: antisense oligonucleotides (asos) and small interfering RNAs (siRNAs).Both ASOs and siRNAs work by reducing the production of apo(a) in the liver. Pelacarsen, an ASO developed by Novartis and Ionis Pharmaceuticals, and siRNAs like olpasiran (Amgen), lepodisiran (Eli Lilly), and zerlasiran (Silence Therapeutics) are among the most promising.
Pelacarsen is currently in a phase 3 trial called Lp(a)HORIZON,involving over 8,300 ASCVD patients with high Lp(a) levels. The trial aims to determine if the drug reduces major cardiovascular events. Phase 2 data showed that pelacarsen could lower Lp(a) levels by about 80% with no major safety concerns.
olpasiran is being studied in the phase 3 OCEAN(a) trial, which has enrolled over 7,200 patients. Phase 2 results demonstrated a 94% reduction in Lp(a) levels after 36 weeks. Lepodisiran is in the phase 3 ACCLAIM-Lp(a) trial, aiming to enroll 12,500 participants with ASCVD or high-risk profiles. Zerlasiran, another siRNA, showed a 96.4% reduction in Lp(a) in a phase 2 study, but its phase 3 program is currently paused.
Muvalaplin, a small molecule inhibitor from Eli Lilly, offers a different approach. Phase 1 data showed it could reduce Lp(a) by up to 65%, with most participants reaching target levels. It is indeed now in phase 2 trials.
“These trials are going to be critical for us to be able to address what we call in the field the Lp(a) hypothesis… We just don’t know how much lowering is enough, and thatS what we’re going to find out,” Koschinsky saeid.
What’s next
The results of these cardiovascular outcomes trials (CVOTs) are eagerly awaited to confirm whether lowering Lp(a) translates into fewer cardiovascular events. These trials will also help determine the optimal level of Lp(a) reduction and identify any potential side effects.