Novartis cholesterol drug pelacarsen fails in major clinical trial

Novartis and Ionis Pharmaceuticals announced that their experimental RNA drug pelacarsen failed a Phase 3 clinical trial of over 8,000 participants, failing to reduce cardiovascular risks despite successfully lowering lipoprotein(a) levels. The failure sent Novartis shares down 3.3% on September 7, 2026, wiping out a potential blockbuster with estimated peak sales of $3 billion to $6 billion. The setback raises the bar for rival lipoprotein(a) therapies from Amgen and Eli Lilly.

Pelacarsen Phase 3 trial failure

• ▪Novartis and Ionis Pharmaceuticals announced on September 4, 2026, that their RNA drug pelacarsen failed to reduce the risk of heart attacks, strokes, and death in a Phase 3 clinical trial
• ▪The Phase 3 clinical trial of pelacarsen included more than 8,000 participants who received either a combination of pelacarsen and standard medications or typical therapies and a placebo

Lp(a) reduction without cardiovascular benefit

• ▪In an earlier clinical trial, pelacarsen decreased lipoprotein(a) levels in study participants by as much as 80% after 24 weeks, according to William Blair analyst Myles Minter
• ▪Novartis Chief Medical Officer Shreeram Aradhye stated that pelacarsen failed to lower cardiovascular risks despite successfully dropping levels of lipoprotein(a) in treated participants

Rival Lp(a) drug programs

• ▪Amgen's experimental lipoprotein(a)-lowering drug reduced lipoprotein(a) levels by more than 95% in mid-stage clinical testing
• ▪Pharmaceutical companies Amgen, Eli Lilly, and Silence Therapeutics are developing alternative therapies to stop genes from making lipoprotein(a) particles or block their formation
• ▪The failure of pelacarsen raises the bar and increases risk for rival lipoprotein(a)-lowering drug candidates currently in late-stage trials by Amgen and Eli Lilly

Financial impact on Novartis pipeline

• ▪Financial analysts had estimated peak annual sales for pelacarsen to be between $3 billion and $6 billion
• ▪Shares of Novartis fell by 3.3% on the morning of September 7, 2026, following the announcement of the pelacarsen clinical trial failure
• ▪The failure of pelacarsen increases pressure on Novartis's upcoming clinical data for del-desiran, an experimental muscular dystrophy drug Novartis acquired for $12 billion in 2025

Lp(a) as cardiovascular risk factor

• ▪According to the American Heart Association, approximately 20% of people have high levels of lipoprotein(a), which cannot be altered through diet or exercise
• ▪Lipoprotein(a) is an inherited, fatty, cholesterol-carrying protein particle linked to heart disease and arterial plaque accumulation

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