Novartis pelacarsen misses primary endpoint in Phase III Lp(a)HORIZON trial

Novartis AG (NYSE: NVS) said its investigational drug pelacarsen did not meet the primary endpoint in the Phase III Lp(a)HORIZON trial, which tested whether treatment could reduce cardiovascular events in patients with elevated lipoprotein(a), or Lp(a), and established cardiovascular disease.

Primary endpoint missed

Novartis AG (NYSE: NVS) said its investigational drug pelacarsen did not meet the primary endpoint in the Phase III Lp(a)HORIZON trial, which tested whether treatment could reduce cardiovascular events in patients with elevated lipoprotein(a), or Lp(a), and established cardiovascular disease.

The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and urgent coronary revascularization requiring hospitalization, compared with placebo. Novartis disclosed the topline results in a September 4 Form 6-K containing an ad hoc press release under Art. 53 LR.

Biomarker lowered, outcomes not

Pelacarsen lowered Lp(a) levels, but the findings did not demonstrate reduced cardiovascular risk in the overall study population. Participants received guideline-directed background therapy, including lipid-lowering and antihypertensive treatment. The result distinguishes lowering the biomarker from demonstrating a cardiovascular benefit in this trial.

Trial size and undisclosed detail

The randomized, placebo-controlled study enrolled 8,323 patients, according to the release's trial description. The primary endpoint was defined for the overall population with Lp(a) of at least 70 mg/dL and a subpopulation with Lp(a) of at least 90 mg/dL. The topline miss was framed around the overall population; the release did not disclose subpopulation outcomes.

Novartis said data would be presented at an upcoming medical congress. The release did not provide hazard ratios or detailed results tables, limiting assessment of the magnitude of the treatment effect or differences across patient groups.

Company context

Shreeram Aradhye, Novartis president of Development and chief medical officer, described the study as a pioneering cardiovascular outcomes trial. He said the results were not what the company had hoped for, while emphasizing their contribution to understanding Lp(a) and thanking the more than 8,000 participants.

Pelacarsen is an investigational antisense oligonucleotide designed to inhibit Lp(a) production. Novartis holds global rights through a license and collaboration with Ionis Pharmaceuticals. Novartis said elevated Lp(a) affects approximately one in five people worldwide and that no targeted treatment is approved.