Novartis pelacarsen trial misses key endpoint

Novartis (NVS) reported on September 4, 2026 that the Phase III Lp(a)HORIZON trial of pelacarsen did not meet its primary endpoint. The study had aimed to show a reduction in the risk of major cardiovascular events compared with placebo but failed to achieve this goal in the overall trial population.

The primary endpoint was a four-point composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and urgent coronary revascularization requiring hospitalization. Results showed no reduction in this composite outcome for patients receiving pelacarsen versus placebo in the overall analysis.

Lp(a)HORIZON was a Phase III, randomized, placebo-controlled, double-blind, parallel-group, multi-center global cardiovascular outcomes trial. It enrolled 8,323 patients with elevated lipoprotein(a) and established cardiovascular disease.

The trial evaluated the primary composite cardiovascular endpoint in two predefined groups: an overall population with Lp(a) levels of at least 70 mg/dL and a subpopulation with Lp(a) of at least 90 mg/dL. All participants received guideline-directed background treatments, including lipid-lowering and antihypertensive therapies.

Pelacarsen is described as an investigational antisense oligonucleotide designed to inhibit Lp(a) production at its source. In Lp(a)HORIZON, treatment with pelacarsen led to lower Lp(a) levels in the study population, but those biomarker reductions did not translate into fewer major cardiovascular events in the overall population.

Novartis (NVS) stated that the complete Lp(a)HORIZON dataset will be presented at an upcoming medical congress. The company highlighted that the findings add to evidence on the relationship between Lp(a) lowering and cardiovascular outcomes, and expressed thanks to more than 8,000 trial participants and investigators.

The announcement included standard descriptions of pelacarsen’s investigational status and forward-looking statements. No additional details on secondary endpoints or subgroup outcomes were provided in the topline update.

Following the topline trial results, Royalty Pharma (RPRX) said it does not anticipate making any pelacarsen-related milestone payments to Ionis (IONS) under their funding agreement. That agreement, signed in January 2023, allocated $150 million of a total $500 million to pelacarsen upside and $350 million to Spinraza royalties.

Royalty Pharma (RPRX) also outlined that its Spinraza royalty interest will revert to Ionis (IONS) after it has received $550 million in royalty payments, representing a 1.1x return on the total funding provided. The company reaffirmed its 2030 Portfolio Receipts target, indicating no change to this long-term objective in light of the pelacarsen outcome.