Pelacarsen, drug designed to lower Lp(a), fails in major trial in setback for heart medicine

The conference at which results were unveiled for pelacarsen, an experimental drug aimed at cutting the risk of heart disease and stroke, was no celebration: many in the hall of doctors already knew it had failed its main goal of reducing major cardiac events by lowering lipoprotein(a), or Lp(a), a sticky fat wrapped in protein.

"This is no near miss. It had no effect on outcomes," said the senior preventive cardiology expert who led the study, the first to test a drug against a condition affecting more than a billion people, and one widely expected to succeed.

The trial randomly split 8,350 patients with high Lp(a) who had previously suffered a heart attack or stroke: half received pelacarsen and half a placebo, double-blind, with most followed for nearly five years. The key measure was major adverse cardiovascular events - cardiac death, non-fatal heart attacks, strokes and emergency procedures for blocked vessels.

When results were unblinded, about 12 per cent of patients in each arm had suffered a major event, even though the drug had cut Lp(a) levels by about 77 per cent on average. The full results, published on Saturday in a leading medical journal, showed no difference in any analysis, including by conditions such as diabetes. Novartis, which had invested hundreds of millions of dollars, has abandoned the drug.

The failure raises hard questions. This year, leading professional bodies recommended for the first time that every adult be tested for Lp(a) at least once, yet no treatment directly addressing high Lp(a) exists. The trial leader suggests the patients may have been too old, or their LDL cholesterol too well controlled by statins, for a benefit to show; stronger Lp(a)-lowering drugs are already in trials and may work better if given before a first heart event.

For now, experts advise people with high Lp(a) to manage every other risk factor: exercise, weight loss and driving LDL cholesterol as low as possible with a statin. "I was thrown from the horse; I will get back on," the trial leader said. "We believe we can help these patients."