An experimental drug can improve a blood test without showing that it helps people avoid a heart attack or stroke. That is the problem facing pelacarsen after a major study in people who already had heart or blood-vessel disease.
The drug is designed to lower lipoprotein(a), usually called Lp(a). This is a particle in the blood whose level is largely inherited. High levels are linked to a greater risk of heart and circulation problems.
Lowering that level was an important step for the drug's developers. The harder test was whether patients receiving the drug would have fewer serious medical problems than patients receiving a dummy treatment.
Daylight Post found that the study's public record made that distinction from the outset. Its main goals concerned what happened to patients. The blood-test result after a year was a separate, secondary goal. We compared those registered goals with the results published on November 7.
What happened to the people in the study
The main analysis covered 8,322 people with high Lp(a) levels and existing heart or blood-vessel disease. They were assigned to monthly injections of pelacarsen or a placebo: an injection that looked the same but did not contain the drug. Both groups continued to receive their usual care.
Patients were followed for a median of 4.7 years: half were followed for longer and half for less time.
Researchers counted several serious outcomes together: death from a heart or circulation problem, a heart attack or stroke that was not fatal, or an urgent procedure to restore blood flow to the heart.
| Treatment | People affected | Share of the group |
|---|---|---|
| Pelacarsen | 511 of 4,157 | 12.3% |
| Placebo | 503 of 4,165 | 12.1% |
The study did not show a reduction in that combined risk. The blood readings were much lower in the drug group after a year, but the result that mattered for patients did not show the hoped-for improvement.
Staying on a treatment matters too
The Cleveland Clinic's account of the trial says reported medical problems led 20.6% of people taking pelacarsen to stop treatment, compared with 7.5% taking the placebo.
The report also gives a separate count of serious medical problems during the trial: 37.3% in the drug group and 41.1% in the placebo group. Stopping treatment because of a problem and having a problem classed as serious are different measures. They should not be read as the same result.
Researchers also looked at results while people were taking the treatment, and among people whose treatment was not interrupted. Those analyses did not establish a benefit either, according to the investigators' report.
Novartis, which paid for the study, had announced in September that the main goal was missed. The November publication provides the detailed results. They concern this drug in patients who already had heart or blood-vessel disease; other Lp(a)-lowering treatments still have to demonstrate their own results.