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.