Novartis and Ionis Pharmaceuticals' Phase III Lp(a)HORIZON trial of pelacarsen failed to reduce a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and urgent coronary revascularization requiring hospitalization versus placebo in the overall study population. Pelacarsen lowered lipoprotein(a), or Lp(a), levels consistently with previous studies, but that reduction did not translate into lower cardiovascular risk. The randomized, placebo-controlled trial involved 8,323 patients with elevated Lp(a) and established cardiovascular disease. Ionis shares fell 6% in aftermarket trading. Royalty Pharma said its $500 million January 2023 funding agreement with Ionis was primarily backed by Spinraza royalties, limiting the financial impact of pelacarsen's failure. The company said it does not anticipate milestone payments, expects to recoup its total investment with a modest positive return, and reiterated a 2030 Portfolio Receipts target of $4.7 billion or more. Novartis plans to present the trial data at an upcoming medical congress. Elevated Lp(a) is an inherited cardiovascular risk factor affecting approximately one in five people worldwide, and no approved targeted treatment is currently available.