Novartis has largely abandoned its experimental cardiovascular drug pelacarsen after a major Phase 3 clinical trial proved entirely neutral, failing to reduce heart attacks, strokes, or cardiovascular deaths despite cutting levels of lipoprotein(a) by roughly 77% to 78%, cnnespanol.cnn.com and Investing.com reported.
Led by Dr. The seven-year study by Novartis included 8,322 patients with pre-existing cardiovascular disease and elevated Lp(a) levels, serving as the industry’s first completed Phase 3 cardiovascular outcomes trial for this biological pathway, though another source noted the trial divided 8,350 individuals randomly into two groups.
- Mechanism of Action: Pelacarsen effectively lowers circulating blood levels of lipoprotein(a), achieving an average reduction of approximately 77% to 78% in clinical subjects.
- Statistical Outcome: Despite successfully hitting its biochemical biomarker target, the Phase 3 trial missed its primary endpoint regarding MACE (major adverse cardiovascular events), showing no measurable reduction in myocardial infarctions, strokes, or cardiovascular mortality.
- Future Pipeline: Following this neutral outcome, Novartis has largely abandoned development of the drug, keeping active only a mid-stage trial evaluating whether the therapy might slow calcific aortic valve stenosis.
The Shocking Results of the Lp(a) Horizon Trial
The findings were presented at the American Heart Association's annual scientific sessions in Chicago and simultaneously published in The New England Journal of Medicine.
Elevated lipoprotein(a) is an inherited, purely genetic risk factor rather than one driven by diet or lifestyle, and it promotes arterial clotting and plaque buildup. However, the trial data showed that even dramatic biochemical reductions in Lp(a) failed to translate into improved survival rates or fewer surgical interventions like coronary artery bypass grafts and stents. Dr. Steven Nissen stated to Bloomberg regarding the findings, No is perjudicial.
Es simplemente neutro por completo.
He also remarked, No estuvo cerca de lograrlo.
Dr. Fatima Rodriguez, chief of preventive cardiology at Stanford University who did not participate in the research, stated, Estoy atónita
. Meanwhile, Dr. Karol Watson, a cardiologist and professor at the David Geffen School of Medicine at UCLA, suggested that promoting universal testing might be premature for now. For the first time this year, the American Heart Association and the American College of Cardiology recommended that all adults undergo an Lp(a) test at least once in their lifetime.
Financial Fallout and Industry Impact for Novartis
Investing.com reported that Novartis has largely abandoned development of pelacarsen, which had previously been projected as a multi-billion-dollar blockbuster. The drugmaker ran the seven-year clinical program. The only remaining clinical evaluation for pelacarsen is a mid-stage trial assessing its potential impact on calcific aortic valve stenosis.
Cardiologists and Wall Street analysts had viewed the Lp(a) pathway as an entirely new pillar for preventive cardiology.
Future Directions in Cardiovascular Genetics
Clinicians continue to recommend established preventive measures, including rigorous LDL cholesterol management via statins, while researchers evaluate alternative therapeutic avenues for genetic cardiovascular risks.
References
- The New England Journal of Medicine: Lp(a) HORIZON Trial Results and Cardiovascular Outcomes.
- American Heart Association: Scientific Sessions and Lipoprotein(a) Screening Guidelines.
- Investing.com: Novartis Corporate Disclosures on Pelacarsen Development.
