PERSPECTIVE
Pelacarsen, an antisense oligonucleotide, lowered lipoprotein(a), or Lp(a), by 78.4% from baseline after one year in the Phase 3 Lp(a)HORIZON trial, compared with 3.2% on placebo. Pelacarsen is a short synthetic strand that targets the messenger RNA liver cells use to make apolipoprotein(a), a component of Lp(a).
The November 7 results also put numbers on the primary endpoint miss Novartis disclosed in September. Over a median 4.7 years, 12.3% of patients on pelacarsen and 12.1% on placebo experienced a major cardiovascular event as defined by the trial. The difference was not statistically significant.
The trial shows how far a drug can move a biomarker without demonstrating a corresponding benefit for patients. For developers of Lp(a)-lowering therapies, it raises the value of trials that measure cardiovascular events directly and specify which patients might benefit.
The participants already had cardiovascular disease and were receiving standard preventive care. Whether other drugs, different patient groups or treatment earlier in the course of disease can reduce cardiovascular events remains open.