Novartis faces Phase 3 setback with pelacarsen trial

Novartis faced a setback in its Phase 3 Lp(a)HORIZON clinical trial evaluating pelacarsen. The drug significantly lowered lipoprotein(a), known as Lp(a), but failed to generate a statistically significant reduction in major cardiovascular events.

Pelacarsen was designed to inhibit the liver's production of apolipoprotein(a) to reduce circulating Lp(a). The large cardiovascular-outcomes study evaluated whether lowering the biomarker translated into fewer clinical events, raising broader questions across the pharmaceutical industry about therapeutic approaches targeting Lp(a).

The drug was originally discovered by Ionis Pharmaceuticals and licensed to Novartis in 2019 for worldwide development and commercialization. Citi analyst Eric Joseph noted that the trial outcome is expected to cause less than 5% immediate downside for Ionis, while not affecting its fiscal 2026 financial guidance.

The trial result also carries strategic implications for competitors such as CRISPR Therapeutics. According to Citi, the outcome could encourage CRISPR to prioritize its preclinical candidate CTX321, which showed approximately twice the potency of CTX320 in preclinical testing, ahead of an expected update in 2026.