On the Horizon: Treatments for Lipoprotein(a)

Awareness of the impact of high lipoprotein(a) as an important genetic risk factor for heart disease is growing. Today, lipoprotein(a) treatments are limited, but there is exciting progress being made with new Lp(a) treatments in clinical studies.

Over the last few months, I have had an increasing number of people referred to me in my lipid clinic wondering if they should have their Lipoprotein (a) [Lp(a)] tested.  Most of these people have a sibling or parent a known elevated Lp(a) and early heart disease or vascular disease.  When these people ask their primary care provider (PCP) about Lp(a), a visit to my clinic is suggested.

It is not surprising that most PCPs don’t know very much about Lp(a).  Although Lp(a) is well-researched, there is still a lot to learn about this complex lipoprotein.  Additionally, although an elevated Lp(a) has been shown to be an important risk factor for the development of cardiovascular disease such as heart attacks and strokes, with the exception of lipoprotein apheresis, there have not been any approved therapies that have been shown both to lower Lp(a) and reduce cardiovascular risk.  Proprotein convertase subtilisin/kexin type 9 inhibitors (better known as PCSK9 inhibitors) have also been shown to lower Lp(a) but are not approved by the FDA specifically for this purpose, only to lower LDL-C.

 

Current Clinical Studies for Lp(a) Treatments

However, there is progress being made to find new treatments for elevated, or high Lp(a). The Lp(a) Association provides a clinical trial search on our web site to simplify the process of searching for studies in your area. Today, we will highlight some of the key studies for Lp(a) treatments.

 

Pelacarsen (TQJ230)

Pelacarsen (also known as TQJ230) has been shown to effectively lower Lp(a) in a number of clinical trials.  Pelacarsen is in the class of medications called “antisense oligonucleotides.”  This class of drugs inhibits the production of Lp(a) and has been shown to lower blood levels of Lp(a) by 70-80%. Based on its ability to significantly lower Lp(a) and an acceptable safety profile, the FDA has approved a cardiovascular outcome trial (CVOT) of pelacarsen in 7,680 patients who have an elevated Lp(a).

  • This multi-country study will determine if a monthly injection of 80 mg of pelecarsen results in a reduction in cardiovascular events compared to a placebo injection.
  • Cardiovascular events of interest include: cardiovascular death, non-fatal heart attack or stroke, or urgent cardiovascular surgery (this would include angioplasty, stents and bypass surgery) requiring a hospitalization.

To be eligible for this study a person must have known vascular disease (history of a heart attack, stroke or symptomatic peripheral artery disease).  This study began recruiting in December of 2019 and is estimated to be concluded in mid-2024. There are currently multiple sites recruiting in 23 states.  A full list of sites can be found through our search.

 

Olpasiran (AMG890)

Olpasiran, also known as AMG890, is a small interfering ribonucleic acid (siRNA) which acts to prevent the production of Lp(a).  Studies comparing 4 different doses of AMG890 to placebo are ongoing in patients with elevated Lp(a).

  • This study will include 240 people who have an Lp(a) > 150 nmol/L.
  • The primary outcome for the study is the percentage change in Lp(a). Other endpoints will include change in low density lipoprotein cholesterol (LDL-C) and apolipoprotein (B).  Apolipoprotein B is a protein found on both LDL and Lp(a).

To be eligible for this study, a person must be over 18 years of age, have a lipoprotein (a) > 150 nmol/L, and have known atherosclerotic cardiovascular disease. There are 10 US sites in 8 states participating in this study.  A full list can be found be found through our search.

 

SLN360

SLN360 is a small/silencing interfering ribonucleic acid (siRNA) which also prevents the production of Lp(a).   Early “first in human” single dose and multi dose studies using SLN360 (100-900 mg by subcutaneous injection) or matching placebo are underway in persons with elevated Lp(a).  These studies will include 88 participants with elevated Lp(a) (>150nmol/L or 60 mg/dL) and will be evaluating the safety, tolerability, pharmacologic properties as well as Lp(a) reducing capacity of SLN360.  This is a single center study.  More information can be found be found through our search.

 

Stay tuned as the story of Lp(a) unfolds.  Should any of these medications be successful at reducing cardiovascular events, the earliest we would expect to see them available by prescription would be around 2025.

 

6 Responses to “On the Horizon: Treatments for Lipoprotein(a)”

  1. Janis Nelson

    Greetings! I attended the FH zoom meeting yesterday with Dr. Tsamikas and found it very informative. In the question list I noticed someone asked about the Pauling Protocol, with which I was unfamiliar. I looked it up and it advocated things I have not heard discussed. Can you comment on the Pauling Protocol? Thank you!
    Janis Nelson

    Reply
    • Amanda Sheldon

      Hi Janis,
      We are asking one of our experts and will get back to you. We are glad you joined the summit session. We will be sharing the video soon.
      Amanda

      Reply
  2. Renee Dyer

    Would you / or someone address diet and fats. I believed Dr Tsamikas said, on FH zoom, studies have shown reducing fats actually increased LPa. I can’t seem to find the correct answer. My LPa is now 157 down from 222 – before Rapatha. I was diagnosed with LPa in 194, at Berkley, with Dr Superko. The LPa has increased over the years, and at 82 would like a couple more years incidence free.

    Reply
    • Amanda Sheldon

      Hello. Yes, we will address diets and fats. What Dr Tsimikas said is that there can be modest effects with some diets on Lp(a) level but that 90% of Lp(a) levels are genetic. We do know that women’s Lp(a) levels increase after menopause. In addition, depending on what other risk factors you have, certain diets wouldbe harmful if they increase your LDL cholesterol.

      Also, this is a great questions for Dr McGowan for our upcoming webinar on March 24. You can find registration details here: https://thefhfoundation.org/webinars

      Reply
  3. Eve

    I have been reading about the possible treatments for LPa over the last 5 years. Wondering how we developed multiple vaccines for COVID in 9 months, and for the better part of the 5 years I’ve been following, there are zero advances in this arena. Given that a far greater percentage of the population with this condition will die than with most other independent risk factors, it seems nothing short of bizarre that progress has not been made. Beyond frustrating.

    Reply
    • Amanda Sheldon

      We understand that it can be frustrating for how long the development cycle can take for new therapies. There are several trials currently underway that show promise. We will also have a webinar later this month and hope you will consider registering to learn more about what is on the horizon: https://thefhfoundation.org/webinars

      Reply

Leave a Reply