Novartis pelacarsen lowered Lp(a) 78% but did not reduce heart attacks in 8,322-patient trial
In the Horizon trial, the injectable drug lowered lipoprotein(a) far more than placebo, yet strokes, heart attacks and cardiovascular deaths did not decline, authors reported.
Results of the Horizon clinical trial of pelacarsen, an experimental injectable drug from Novartis, were presented on Saturday at a meeting of the American Heart Association and published in the New England Journal of Medicine, according to lomazoma.com lomazoma.com
lomazoma.comlomazoma.comOpen source ↗. The drug did not reduce strokes, heart attacks, cardiovascular deaths or the number of procedures to reopen blocked arteries or restore blood flow to the heart. The trial enrolled 8,322 people with high Lp(a) who had already had a heart attack, stroke or another heart problem; nearly 800 sites took part.
Lipoprotein(a) and the trial results
Pelacarsen targets lipoprotein(a), or Lp(a). Like LDL, Lp(a) promotes plaque formation in the arteries, but it also helps form blood clots and, unlike LDL, is entirely genetic. According to the American Heart Association, about one in five Americans has a high Lp(a) level, and most do not know it. Diet and exercise do not affect it.
The drug lowered Lp(a) by 78%, compared with 13% in the placebo group, but this did not translate into better cardiovascular outcomes. The trial was led by Dr. Steven Nissen of the Cleveland Clinic, who said the results were extremely surprising. In his words, there is no evidence that people with a larger reduction did better.
Possible explanations and other drugs
Dr. Karol Watson of UCLA, who was not involved in the study, suggested the therapy may have come too late in life. Participants averaged 60 years of age and were followed for an average of five years. They were also treated aggressively for LDL cholesterol and blood pressure, and may have taken aspirin, which could have reduced the clotting risk. How much Lp(a)-related risk remained is unknown, Watson said lomazoma.com
lomazoma.comlomazoma.comOpen source ↗.
Earlier this year the American College of Cardiology and the American Heart Association issued guidelines recommending a one-time Lp(a) blood test for every adult. Dr. John Wilkins of Northwestern Medicine, one of the guideline authors, said Lp(a) remains a robust marker of cardiovascular risk.
Nissen said no further pelacarsen trial is planned. Similar injectable drugs are in development: lepodisiran from Eli Lilly, olpasiran from Amgen and zerlasiran from Silence Therapeutics. Pelacarsen is an antisense oligonucleotide, while the others use small interfering RNA and, according to Nissen, may cause fewer side effects such as injection-site reactions. Clinical trials are under way to test whether they affect heart health. Eli Lilly is also studying an oral drug, muvalaplin, and CRISPR gene editing to permanently switch off the Lp(a) gene is at an early stage of development.
