Novartis drug lowered Lp(a) but failed to prevent cardiovascular events

An RNA drug jointly developed by Novartis and Ionis Pharmaceuticals failed to demonstrate a preventive effect against cardiovascular disease in a large clinical trial.

According to BioPharma Dive on the 5th (local time), pelacarsen failed to reduce the risk of heart attack, stroke or death despite substantially lowering lipoprotein(a) levels.

Pelacarsen is designed to rapidly lower levels of lipoprotein(a), or “Lp(a),” a protein particle known to be associated with heart disease.

In a phase 3 clinical trial involving more than 8,000 participants, the group that received pelacarsen alongside standard treatment did not have a lower risk of major cardiovascular events than the group that received standard treatment and placebo.

Novartis said in a statement that day that it had not disclosed specific figures and that the results would be presented at a future scientific conference.

Chief Medical Officer Shriram Aradhye said, “This is not the result we had hoped for,” but added that the findings “could help inform future approaches to cardiovascular care.”

According to the American Heart Association (AHA), about 20% of people have elevated Lp(a) levels, making them more likely to develop harmful plaque buildup in their arteries.

However, Lp(a) levels cannot be controlled through diet or exercise, and doctors do not routinely test for them because no approved drugs are available to lower them.

Pelacarsen was the most advanced drug candidate among therapies designed to lower Lp(a).

William Blair estimated that, if successful, the drug could generate annual sales of up to $6 billion in the United States alone.

Miles Minter, an analyst at William Blair, said the failure raised questions about the cardiovascular benefits of lowering Lp(a) and represented “significant risk” for other ongoing clinical trials.

Minter said pelacarsen lowered Lp(a) levels by as much as 80% after 24 weeks in an earlier trial and, citing conversations with Ionis executives, reported that a similar degree of reduction was observed in this study.

He added that there could be opportunities for approaches seeking “deeper Lp(a) suppression.”

Eli Lilly, Amgen and Silence Therapeutics are developing drugs that use different approaches, including preventing genes from producing Lp(a) or blocking its formation.

Amgen’s drug lowered Lp(a) by more than 95% in a midstage trial.

Jefferies analyst Dennis Ding said he would focus on the “correlation” among Lp(a) levels at the start of the study, the magnitude of the reduction and clinical benefit.

“This will be important data to dig into,” Ding said.