HOPES for a new treatment targeting an inherited cause of heart disease have suffered a setback after pelacarsen failed to reduce cardiovascular deaths, heart attacks or strokes.
The experimental drug, developed by Novartis and Ionis Pharmaceuticals, had been expected to become the first in a new generation of medicines targeting lipoprotein(a), or Lp(a), a cholesterol-carrying particle linked to increased cardiovascular risk.
However, detailed results presented at the American Heart Association’s annual meeting on 7 November showed that lowering Lp(a) by approximately 78% offered no protection against serious cardiovascular events compared with placebo.
Setback for Inherited Heart Risk Treatment
Elevated Lp(a) affects approximately one in five people worldwide. Levels are largely determined by genetics, and there is currently no approved medicine specifically targeting the particle.
Researchers had hoped that reducing Lp(a) would prevent heart attacks and strokes, offering patients another treatment alongside medicines that lower LDL cholesterol and control blood pressure.
Instead, patients receiving pelacarsen experienced almost identical rates of serious cardiovascular events to those given placebo in trials, despite substantial reductions in their Lp(a) levels.
The trial followed more than 8,300 people with existing cardiovascular disease for a median of 4.7 years. Cardiovascular death, non-fatal heart attack, stroke or an urgent procedure to restore blood flow occurred in 12.3% of patients taking pelacarsen, compared with 12.1% receiving placebo.
The setback comes as cardiovascular disease remains the leading cause of death in Europe. According to the World Health Organization, cardiovascular diseases account for approximately 10,000 deaths every day across its European Region, representing 42.5% of all deaths.
Heart attacks and strokes account for most of these fatalities, with a higher burden in eastern parts of the region.
Unlike several other cardiovascular risk factors, elevated Lp(a) is largely inherited and changes little with diet or exercise.
However, identifying high levels can help inform a patient’s overall cardiovascular risk assessment. Controlling blood pressure, lowering LDL cholesterol and addressing smoking and physical inactivity remain established ways to reduce cardiovascular risk while targeted treatments continue to be investigated.
The findings of this latest study also came alongside another setback for cardiovascular treatment, with Novo Nordisk’s anti-inflammatory drug ziltivekimab also failing to improve outcomes.
Although the medicine reduced inflammation in approximately 6,300 patients with heart disease, advanced kidney disease and systemic inflammation, it did not reduce deaths, heart attacks or strokes compared with placebo.
Novo Nordisk has also ended two related late-stage trials involving patients with heart failure and inflammation after an independent monitoring committee concluded they were unlikely to succeed.
Pelacarsen’s failure leaves patients waiting for a treatment that can turn reductions in Lp(a) into fewer cardiovascular events – if possible at all. It also raises questions about how far levels need to fall, and whether treatment must begin before cardiovascular disease becomes advanced.
Other medicines targeting Lp(a), including Amgen’s olpasiran and Eli Lilly’s lepodisiran, remain in development. They work differently from pelacarsen and have achieved larger reductions in Lp(a) in earlier research.
Their ongoing trials will help establish whether a different approach, or treatment before a first heart attack or stroke, can deliver the benefits pelacarsen failed to show.
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