Novartis Lp(a) drug fails to lower cardiovascular risk in closely watched ph. 3 trial
Sep 4, 2026 9:18pm
Lp(a) has had the medical community’s attention for quite some time. It’s been found that significant elevations in Lp(a) are strongly associated with heart attacks, so much so that the test is actually part of the MDVIP Annual Wellness Exam panel. The results of Lp(a) testing allows us to be risk, stratified into “high, medium, and low” risk for heart attacks. So of course the thought is that is it actually a player and not just a spectator.
There are drugs currently on the market that decrease Lp(a) but these are accidents. Repatha and drugs like it work by decreasing normal cholesterol for patients who do not tolerate statins or patients who need more help than a maximum dose statin can provide. These medications also were found to decrease Lp(a) by around 25 to 30% depending on which drug you’re looking at.
However, while these PCSK9 drugs can improve outcome, the Lp(a) effects were not designed into the structure of the drug and were instead, just noticed as an after effect. This amount of decrease is not thought to be enough to help a patient avoid a stroke or heart attack, strictly from decreasing the Lp(a) alone.
So What? New drugs have been designed to specifically attack and drop the levels of Lp(a). They do this by creating a specific RNA message that blocks the production of Lp(a).
I am a sub investigator on Eli Lilly‘s Lp(a) drug and have roughly 20 patients currently in this trial. This article discusses the fact that while the new medication from Novartis drops Lp(a) by 72%, it did NOT change heart attack and stroke risk. There was no outcome benefit, rather, the numbers on a piece of paper got better.
There have been those in the medical community who are disappointed in this outcome. Personally, I wasn’t very surprised by the data. This is because my medical philosophy is that inflammation is the cause of cardiac disease, not cholesterol and cholesterol by products. I believe that the creation of the inflammation creates the cholesterol and cholesterol byproducts, which means that they’re elevated when inflammation is elevated, however, I do not believe they are active players in the cause of disease. The results from this test would also support that.
Further, when other drugs in the past decrease the amount of cholesterol in your body after the cholesterol has been manufactured there is little changing outcome.
https://pubmed.ncbi.nlm.nih.gov/26043746/(opens in new tab)
So the disappointing results are that at least with the first large, phase 3 trial with Lp(a), changing Lp(a) numbers by directly blocking the manufacture of Lp(a) did not improve outcome. While the Eli Lilly trial is still underway it does paint a disappointing picture and dampen expectations – at least in my mind.
Interestingly of note, it was incidentally found that women who go through estrogen hormone replacement therapy actually DO decrease their Lp(a) by 14%.