Full Breakdown
Novartis’ Pelacarsen Fails to Show Cardiovascular Benefit in Late-Stage Trial
9/10/2026, 12:35:43 AM
Core Event: Phase 3 Lp(a)HORIZON Trial Misses Primary Endpoint
Novartis announced that its antisense therapy pelacarsen, developed with Ionis Pharmaceuticals, did not achieve a statistically significant reduction in major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or urgent coronary revascularization) compared with placebo. The Phase 3 Lp(a)HORIZON study enrolled more than 8,000 patients with established cardiovascular disease, and a separate report tracked over 8,300 participants. While the drug lowered circulating lipoprotein(a) [Lp(a)] levels, the primary clinical endpoint was not met.
Background & Context
Lp(a) is a genetically determined cholesterol variant linked to plaque buildup and clot formation. Discovered in 1963, elevated Lp(a) is estimated to increase heart-attack risk more than two-fold and is largely unaffected by diet or exercise. No therapy targeting Lp(a) has received regulatory approval. Novartis’ mid-stage studies showed up to an 80 % reduction in Lp(a) versus placebo, prompting a partnership with Ionis under an August 2023 agreement. Competing approaches from Amgen (siRNA olpasiran) and Eli Lilly (siRNA lepodisiran) also aim to lower Lp(a) and are in late-stage trials.
Data & Statistics
- Trial size: >8,000 patients (Lp(a)HORIZON); >8,300 tracked in detailed reporting.
- Biomarker effect: up to 80 % Lp(a) reduction in earlier studies.
- Market expectations: analysts had modeled peak annual sales of $4 billion to $5 billion for a successful pelacarsen.
- Share reactions: Novartis shares fell 3 %–4 % in after-hours trading; Ionis shares dropped 10 %; Amgen shares fell 5 %; NewAmsterdam Pharma shares fell 12 %.
- Industry impact: The setback is viewed as the first major outcomes failure for a dedicated Lp(a)-lowering therapy, raising uncertainty for the multibillion-dollar drug class.
Official Statements & Responses
Novartis chief medical officer **Dr. The company indicated that full trial data will be presented at an upcoming medical congress.
Analyst Perspectives (Criticism & Opposition)
- Barclays observed that “the market was expecting a moderate benefit, if not transformational blue-sky result,” and that pelacarsen
Why It Matters / Impact
The trial outcome erodes confidence across the Lp(a)-lowering class, potentially delaying or reshaping development timelines for competing siRNA programs. Amgen’s olpasiran now faces “higher-risk/higher-reward” scrutiny, while Lilly’s lepodisiran, tested in a broader patient population, may be less directly affected but still confronts heightened investor skepticism. The broader market impact includes a short-term erosion of billions in combined market capitalization for the companies involved and a reassessment of the commercial viability of targeting Lp(a) as a therapeutic strategy.
What’s Next
- Amgen’s OCEAN(a) study of olpasiran is slated for a topline readout in 2028.
- Eli Lilly’s ACCLAIM-Lp(a) trial of lepodisiran expects initial data in 2029.
- Novartis plans to disclose detailed efficacy and safety data at a forthcoming medical meeting, which may clarify whether the biomarker reduction can be decoupled from clinical outcomes.
