Cardiology just took back-to-back blows to two of its most promising prevention strategies. One drug for lowering lipoprotein(a) and another targeting interleukin-6 both failed in major trials, even as fresh data reaffirms just how much those factors matter.
This begs the question: are these molecules CVD causes or merely biomarkers?
- First, Novartis announced that pelacarsen, its Lp(a)-lowering drug failed to show a CV risk benefit in its 7-year, 8,000-patient Phase 3 trial.
- Then, Novo Nordisk decided to abandon its IL-6 inhibitor ziltivekimab across multiple trials after the ZEUS study showed the drug failed to provide a meaningful MACE benefit.
Not to be dramatic, but Novartis’ Phase 3 pelacarsen failure genuinely stunned cardiologists.
- That’s because an earlier study showed the drug cut Lp(a) by 80%, making future CV benefits seem certain.
- Now its failure casts doubt on similar trials underway at Amgen and Eli Lilly.
- Some physicians called it a “big bust” while others quickly criticized everything from the drug’s design to the trial’s patient population.
Novo’s IL-6 collapse was less of a blindside but the company’s decision to wrap up the Hermes and Athena heart failure trials early due to ZEUS’ failure rains heavily on the inflammation parade.
- Analysts once dubbed ziltivekimab a $3B drug, due to its ability to effectively lower IL-6 levels.
- But Novo’s choice to jump ship undercuts that potential alongside the inflammation-driven CVD hypothesis.
- Novo’s last ziltivekimab trial standing is Artemis, a post-MI trial reading out in the first half of next year.
Ironically, the science backing these studies looks stronger than ever. A recent JAMA study reinforced both risk factors and even tied them together.
- That study found that IL-6 significantly modifies Lp(a)-associated coronary artery disease risk.
- As a result, patients with the highest combined Lp(a) and IL-6 levels faced a 34% higher CAD risk than those with lowest levels.
- Thus, it seems like the two pathways interact, and inflammation amplifies Lp(a)’s danger.
The Takeaway
Here’s the moral of the story – strong association is not causation, because both pelacarsen and ziltivekimab successfully lowered their respective biomarkers but didn’t change cardiovascular outcomes. With these trial failures, it might be time to reconsider our understanding of CVD risk factors and the molecules we target to fight heart disease.
