Novartis pelacarsen fails primary endpoint in Lp(a)HORIZON trial
- Novartis pelacarsen fails primary endpoint in Phase III Lp(a)HORIZON trial
- Drug achieved substantially lower Lp(a) levels but did not reduce cardiovascular events
- Trial involved 8,323 patients with elevated Lp(a) and established cardiovascular disease
- Ionis notes results provide clarity to inform future cardiovascular care strategies
*this image is generated using AI for illustrative purposes only.
Novartis announced on September 4, 2026, that its Phase III Lp(a)HORIZON trial for pelacarsen did not meet its primary endpoint. The study failed to demonstrate a reduction in cardiovascular events compared to placebo.
The trial evaluated pelacarsen, an investigational antisense oligonucleotide licensed from Ionis Pharmaceuticals, in patients with elevated lipoprotein (a) and established cardiovascular disease. Despite achieving lower Lp(a) levels, the drug did not translate this biomarker reduction into improved clinical outcomes for the overall population.
Trial Design and Results
Lp(a)HORIZON was a randomized, placebo-controlled, double-blind global study involving 8,323 patients. The primary endpoint measured a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and urgent coronary revascularization requiring hospitalization.
Participants were receiving guideline-directed treatments, including lipid-lowering and antihypertensive therapies. The study assessed outcomes in two groups: the overall population with Lp(a) levels ≥70 mg/dL and a subpopulation with levels ≥90 mg/dL.
| Trial Parameter | Detail |
|---|---|
| Study Name | Lp(a)HORIZON (NCT04023552) |
| Phase | III |
| Participants | 8,323 patients |
| Primary Endpoint | Composite cardiovascular events |
| Result | Did not meet primary endpoint |
What the Numbers Show
The data reveals a divergence between pharmacological efficacy and clinical benefit. While pelacarsen successfully inhibited Lp(a) production at its source, resulting in lower biomarker levels, this reduction did not correlate with a decrease in major adverse cardiovascular events. This suggests that simply lowering Lp(a) may not be sufficient to reduce residual cardiovascular risk in patients already on optimized care.
Shreeram Aradhye, President of Development and Chief Medical Officer at Novartis, stated that the findings provide important evidence on the relationship between Lp(a) lowering and cardiovascular outcomes. Brett P. Monia, CEO of Ionis, noted that while the study did not meet its primary endpoint, the results provide clarity that will meaningfully inform future cardiovascular care.
Future Steps
Novartis plans to present the Lp(a)HORIZON data at an upcoming medical congress. The company emphasized its continued commitment to cardiovascular innovation despite the negative results. Pelacarsen remains an investigational therapy with no approved targeted treatment currently available for elevated Lp(a). Ionis continues to drive the independent commercialization of its wholly owned medicines TRYNGOLZA, DAWNZERA and ZANVASTRO.
Historical Stock Returns for Novartis
| 1 Day | 5 Days | 1 Month | 6 Months | 1 Year | 5 Years |
|---|---|---|---|---|---|
| +11.29% | +17.39% | +13.36% | 0.0% | 0.0% | +117.89% |
How will the failure of pelacarsen impact Novartis' and Ionis' stock valuations and their respective R&D pipelines for lipid-lowering therapies?
Will this negative outcome prompt regulatory bodies or clinical guidelines to reconsider Lp(a) as a primary therapeutic target, or shift focus toward other residual risk markers?
Are there specific patient subgroups within the trial data that showed benefit, potentially allowing for a narrower label approval or repurposing of the drug?
19
Access Market Heat-map & Insights 
Create, Save & Share your Screener 
Use 200+ Screening Filters 
