NYT told about the failure of drugs that promised a “new era” in cardiology

Two experimental drugs for the prevention of cardiovascular disease – pelakarsen from Novartis and ziltivekimab from Novo Nordisk – were no more effective than placebo. The full results of clinical trials showed that the drugs did not reduce the risk of heart attacks and strokes in any group of patients. The data was presented at the annual meeting of the American Heart Association and published in The New England Journal of Medicine.

The development of drugs was accompanied by high expectations: scientists expected that they would open new approaches to the prevention of heart disease. Pelakarsen reduces levels of lipoprotein (a), a blood particle that has been linked to the risk of heart attacks and strokes. Ziltivekimab also suppresses inflammation, presumably involved in the formation of plaques in the arteries. The article notes that “huge funds” were invested in the development of these drugs, which were expected to open a “new era” in the prevention of cardiovascular disease.

The Zeus study on ziltivekimab involved 6,376 people with severe heart and kidney disease. The drug did reduce inflammation, but the risk of serious cardiovascular complications in patients receiving it was almost the same as in the placebo group. No positive effect was found in any of the subgroups.

Dr. Paul Ridker, who led the study, who had previously been “sincerely convinced of success” and considered Zeus a “brilliant idea,” admitted that scientists might have chosen the wrong biological target or group of patients. Perhaps the participants' illnesses went too far for treatment to help them. "Maybe the train has already left," he suggested.

Other experts have questioned the very hypothesis about the role of inflammation in the development of cardiovascular disease. “The whole cardiology community was just stunned,” said Carol Watson, program manager for preventive cardiology at the University of California, Los Angeles (UCLA).

In September, Novo Nordisk announced it was halting two other studies of ziltivekimab in patients with heart failure due to lack of effect. At the same time, the company continues to test the drug on patients who have had a heart attack. Their results are expected next year.

Meanwhile, the failure of pelakarsen has also raised questions about the promise of drugs that lower lipoprotein (a). Horizon Project Principal Investigator Stephen Nissen of the Cleveland Clinic fears the findings could force patients to opt out of two other trials of similar drugs. “One study doesn’t necessarily answer all the questions,” he said.

Among the possible reasons for the failure, experts, in addition to the factor of too late stage of the disease, also called good control of other risk factors - pressure and cholesterol - and taking drugs that could neutralize the effect of pelakarsen.

Nissen stressed that elevated levels of lipoprotein (a) remain a serious risk factor. However, the study itself found no evidence of the benefit of Novartis. "Is there anything you could point to and say, "Yes, there's a benefit here?"" Nissen asked. “No, there was nothing like that,” he said.