5 Promising Lipoprotein(a) Treatments in Development: Pelacarsen, Olpasiran, and More

If you have high cholesterol, you’ve likely heard all about statin medications, such as atorvastatin (Lipitor). The benefits of routine exercise and a heart-healthy diet may also be recurring conversations you have with your healthcare provider. But for those with high lipoprotein(a) levels — also known as high Lp(a) — the best way to tackle your cholesterol may look a little different.

Lp(a) is a special form of cholesterol. It’s an especially sticky version of LDL (“bad”) cholesterol. If you have too much of it, it can raise the risk of problems such as heart disease, blood clots, and heart valve issues. What’s more, unlike other types of cholesterol, high amounts of Lp(a) don’t usually respond to medications like statins or healthy lifestyle changes.

However, some hope is on the horizon. Even though there aren’t any FDA-approved Lp(a) medications yet, this could change in the not too distant future. Several Lp(a)-lowering medications are being studied in clinical trials. Researchers believe that lower Lp(a) levels can reduce the odds of developing heart-related health problems.

Five of the most promising lipoprotein(a) treatments are highlighted below.

1. Pelacarsen

Pelacarsen is a Lp(a) medication that’s in phase 3 clinical trials — the last stage of testing before a drug manufacturer applies for FDA approval. It used to be called TQJ230 and IONIS-APO(a)-LRx, among other names.

Pelacarsen is given as a once-monthly injection under the skin. If approved, you’d be able to administer the shot yourself at home. Pelacarsen works as an “antisense” medication; it acts like a small strand of DNA that disrupts Apo(a)-producing mRNA in the liver. Apo(a) is an important protein inside of Lp(a); so without it, your body can’t make new Lp(a).

Early estimates suggest that 80 mg doses of pelacarsen can lower Lp(a) by as much as 67% compared to placebo (an injection with nothing in it). Different data shows it can lower Lp(a) by up to 80%.

While these results are encouraging, experts are still learning about pelacarsen’s safety and effectiveness. Pelacarsen’s 8,000-person, phase 3 study is set to run until May 2025. If data from this study is positive, an FDA approval application will likely follow suit.

Good to know: Another phase 3 study is looking to see if pelacarsen can reduce the need for lipoprotein apheresis. This is a weekly procedure that manually removes Lp(a) from the bloodstream. But given its limited availability and cost, apheresis is not an accessible treatment option for most people.

2. Olpasiran

Olpasiran is a different Lp(a) medication that’s enrolled in phase 3 studies. It has some similarities to pelacarsen, but they’re not one in the same.

Olpasiran (formerly “AMG 890”) is injected under the skin once every 12 weeks (3 months) — not every month. And while it also interferes with mRNA, it does so in a slightly different way. Olpasiran is a siRNA medication that links with a specific group of proteins in liver cells. Together, they work to find and break apart Apo(a)-producing mRNA. This leads to a drop in Lp(a) levels.

Preliminary data is positive for olpasiran. A recent phase 2 study suggests that doses of 75 mg or higher can lower Lp(a) levels by over 95%. A 6,000-person, phase 3 trial started in December 2022 and it’s scheduled to run until December 2026.

3. Zerlasiran

Zerlasiran (SLN360) is another siRNA medication. It works the same way as olpasiran. But it’s made by a different company, and it’s working through clinical trials at a different pace.

Zerlasiran is an injectable medication that’s administered under the skin. Like olpasiran, it appears to be an effective treatment option. Early, phase 1 data suggests a single dose can lower Lp(a) levels by up to 98%. Data from multiple doses of zerlasiran is expected to be announced by late 2023.

Larger, more advanced studies are up next. A phase 2 study finished enrolling participants in May 2023. The study itself is scheduled to be completed by June 2024, and results should be released soon after. A phase 3 trial should follow suit.

4. LY3819469

LY3819469 is following in the footsteps of olpasiran and zerlasiran. It’s a siRNA medication that works in a similar fashion.

A phase 1 study of this medication finished up in November 2022. The main purpose of this study was to see if this under-the-skin injectable product is safe and well tolerated. A phase 2 study is expected to run until October 2024. If everything goes to plan, a phase 3 study would be on deck.

Good to know: “LY3819469” won’t be the medication’s final name. This is a temporary name that’s used during the drug development process. Assuming it continues to progress through clinical trials, the medication will eventually be given a more traditional drug name.

5. Muvalaplin

Muvalaplin (LY3473329) is a once-daily oral pill. The fact that it’s not an injectable medication is a big part of what makes it unique. Muvalaplin’s manufacturer describes it as a chemical that disrupts Lp(a) formation, but not much is widely known about how it specifically does this.

Similar to LY3819469, muvalaplin is in early to mid stages of development. A phase 1 safety and tolerability study is already under wraps. A phase 2 trial kicked off in November 2022, and it’s set to end by January 2024.

Muvalaplin is being developed by Eli Lilly, the same company as LY3819469.

How is high lipoprotein(a) currently treated?

High Lp(a) levels are caused by your genetics, not your diet or lifestyle. So, without any FDA-approved medications available, treatment for high Lp(a) levels focuses on minimizing other risk factors for heart disease.

Even though you can’t change your Lp(a) levels, heart-related risk factors that you can control include:

• High cholesterol

• High blood pressure

• Diabetes

• Smoking

Inflammatory health conditions, such as rheumatoid arthritis, have also been linked to higher Lp(a) levels. So treating these conditions may indirectly improve Lp(a). Hypothyroidism and certain types of chronic kidney disease have also been linked to higher Lp(a).

As mentioned above, weekly lipoprotein apheresis sessions are another management tool. It’s an effective treatment — especially for severe cases of high Lp(a). It’s even FDA approved for this purpose. But it can be time-consuming, expensive, and hard to find treatment centers that use it. So it’s not always a first-choice or realistic option.

Are medications ever used for high lipoprotein(a) levels?

Sometimes, depending on the situation. These medications are sometimes taken off label in attempt to lower Lp(a):

• PCSK9 inhibitors such as Repatha (evolocumab) and Praluent (alirocumab) may lower Lp(a) by up to 30%.

• Leqvio (inclisiran), a siRNA medication that’s similar to PCSK9 inhibitors, may lower Lp(a) by up to 26%.

• Niacin may lower Lp(a) levels in some people, but it has mixed safety and effectiveness data.

• Estrogen can help reduce Lp(a), but it’s not widely recommended because of its heart effects.

Why trust our experts?

Written by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Reviewed by:

Katie E. Golden, MD

Katie E. Golden, MD, is a board-certified emergency medicine physician and a medical editor at GoodRx.

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