Novartis, Ionis heart drug fails in major Phase 3 trial

Novartis and Ionis Pharmaceuticals announced their experimental drug pelacarsen failed a major Phase 3 clinical trial. The drug did not lower the risk of heart attacks, strokes, or death in a study of more than 8,000 participants, according to a Friday statement from Novartis.

The drug was designed to sharply lower levels of a protein particle called lipoprotein(a), or Lp(a). Scientific research has linked high levels of Lp(a) to heart disease. In the multiyear trial, participants received pelacarsen plus standard medications or typical therapies plus a placebo. The combination with pelacarsen showed no added benefit in preventing major cardiovascular events.

Novartis did not provide specific numerical results from the study, stating they will be presented at an upcoming medical meeting. Chief Medical Officer Shreeram Aradhye said in the statement, "These are not the results we hoped for." He added that the findings could "help inform future approaches to cardiovascular management." The negative outcome occurred even though pelacarsen successfully lowered Lp(a) levels in the treated participants.

The Lp(a) target and unmet need

Genetic and epidemiological studies have shown a link between Lp(a) and heart disease. The American Heart Association states about 20% of people have high levels of Lp(a). These individuals are more likely to have harmful plaques build up in their arteries. Unlike cholesterol, people cannot lower their Lp(a) through diet or exercise. Physicians also rarely test for it because, until now, there have been no approved medications to treat it.

Several large drugmakers have been racing to develop therapies that can drastically reduce Lp(a). Pelacarsen was the most advanced candidate in this emerging class. Its Phase 3 failure is a significant setback for this approach to cardiovascular protection.

Commercial and clinical implications

The trial's failure has major consequences for Novartis. Pelacarsen was one of a handful of prospects the company hoped would offset upcoming patent expirations on key products. Analysts at William Blair had previously estimated the drug could achieve $6 billion in peak annual U.S. Sales alone if successful.

The negative results also raise questions about the broader strategy of targeting Lp(a). In a Friday research note, William Blair analyst Myles Minter wrote the outcome suggests there is "meaningful risk" in other ongoing trials of similar drugs. He noted that in an earlier trial, pelacarsen decreased Lp(a) levels by as much as 80% after 24 weeks. For the latest study, while specifics were not provided, reductions were "in the range previously observed," according to Minter's team after speaking with Ionis management.

The competitive landscape and future questions

Minter suggested there might still be an opportunity for drugs that achieve deeper Lp(a) inhibition. Other companies are advancing candidates that use different methods. Their approaches aim to stop genes from making Lp(a) particles or block their formation.

Analysts say detailed study data will be important. Jefferies analyst Dennis Ding wrote his team will look for any correlation between patients' starting Lp(a) levels, the magnitude of reduction, and clinical benefit. They will also examine how close pelacarsen came to succeeding and the statistical impact of patients who did not complete the trial. "This will be an important dataset to dig into," Ding wrote.

Novartis and Ionis now await the full presentation of the data, which the cardiovascular research community will scrutinize closely.