Novartis just announced the top-line results of Lp(a) HORIZON, its big Phase 3 trial of pelacarsen. The drug held promise as potentially the first approved therapy targeting lipoprotein(a), a cholesterol particle tied to heart attack and stroke risk. The study showed pelacarsen worked in lowering those levels. It did not, however, reduce cardiovascular events.
The announcement comes just weeks after the letdown of ZEUS, a Phase 3 trial evaluating Novo Nordisk’s ziltivekimab, a monoclonal antibody targeting IL-6 as an anti-inflammatory agent. That one was also successful in impacting its biological target. It also failed to change clinical outcomes.
Both studies followed the same pattern. They showed the drugs did what they were supposed to do to their targets. Neither showed the expected benefit in patients.
What the Trials Showed
Lp(a) HORIZON tested pelacarsen on lipoprotein(a). The study proved the drug could lower those levels. It did not, however, move the needle on cardiovascular events.
ZEUS tested ziltivekimab on IL-6. That study proved the antibody could affect its target. It also failed to change clinical outcomes.
Both studies showed success against their biological targets. Neither showed success against the disease itself.
The Pattern Is Familiar
These results join a growing list of trials that have lowered a target but failed to improve patient health. Each one raises the same question: what is the point of lowering a biomarker if the patient gets no better?
The pattern has appeared across multiple targets and multiple diseases. Each time, the result is the same: the marker moves, the outcome stays the same.
Why This Matters
Preventive cardiology depends on finding markers that predict trouble and treating them before trouble happens. Precision medicine depends on targeting specific biological pathways. Both approaches rely on the assumption that hitting the right marker will produce the right result.
These trials suggest that assumption may be wrong. A drug can lower a marker without changing the course of the disease. That is a problem for researchers, regulators, and patients alike.
The evidence of their benefit is thin. Doctors now face a choice: prescribe an expensive treatment with an uncertain effect, or wait for better data.
What Comes Next
The field now faces a moment of reckoning. Researchers must ask whether their markers actually matter. Regulators must ask whether lowering a marker counts as a meaningful advance. Patients must ask whether a drug that lowers a number improves their life.
The answer so far is not encouraging. Two major trials have shown the same thing: a drug can hit its target without helping the patient.
The pattern is consistent across the field. Each trial adds to the weight of evidence that biomarkers alone are not enough.
The View From STAT+
STAT+ subscribers got exclusive access to this analysis. The full piece, with in-depth analysis, newsletters, premium events, and news alerts, is available to them.
The article’s judgment is clear: the field needs to rethink what counts as success. Lowering a marker is not the same as curing a disease. The distinction matters for every doctor, every patient, and every dollar spent on research.
The stakes are high. The data are clear. The moment of reckoning has arrived.
| Trial | Target | Result |
|---|---|---|
| Lp(a) HORIZON | Lipoprotein(a) | Marker lowered, events unchanged |
| ZEUS | IL-6 | Target affected, outcomes unchanged |
- Lp(a) HORIZON: pelacarsen, lipoprotein(a), marker lowered, events unchanged
- ZEUS: ziltivekimab, IL-6, target affected, outcomes unchanged
The pattern holds. The conclusion follows.
Source material: “Opinion: STAT+: A moment of reckoning for preventive cardiology and the precision medicine revolution,” STAT.
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