Failure of Novartis Lp(a) drug raises questions about cardiovascular strategy

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1. 1h ago

   Novartis abandons pelacarsen after Lp(a)HORIZON trial failure

   Novartis has discontinued development of pelacarsen, its lipoprotein(a)-lowering antisense drug, after the Phase 3 Lp(a)HORIZON trial showed no reduction in major cardiovascular events versus placebo despite significantly lowering Lp(a) levels. The trial enrolled patients with established cardiovascular disease and elevated Lp(a). Full results presented at the American Heart Association meeting on November 7 confirmed the lack of benefit in secondary prevention. This follows a similar setback for Novo Nordisk's ziltivekimab, another inflammation-targeting cardiovascular candidate, leaving researchers questioning the therapeutic strategy of targeting residual risk factors beyond LDL cholesterol.

   Why it matters

   Lipoprotein(a) is a genetically determined, independent risk factor for heart attack and stroke that affects an estimated 20-25% of the global population. Pelacarsen was the most advanced drug specifically designed to lower Lp(a) using antisense technology, and its failure challenges the hypothesis that pharmacologically reducing Lp(a) in patients with existing cardiovascular disease will translate into clinical benefit. The outcome also raises broader questions about cardiovascular drug development pathways that rely on surrogate biomarkers rather than outcomes data.

   What is confirmed

   • Novartis discontinued development of pelacarsen after the Phase 3 Lp(a)HORIZON trial failed to meet its primary endpoint.
   • The trial tested pelacarsen in patients with established cardiovascular disease and elevated lipoprotein(a) levels.
   • Pelacarsen significantly lowered Lp(a) levels but did not reduce major adverse cardiovascular events versus placebo.
   • Full trial results were presented at the American Heart Association meeting on November 7, 2026.
   • Novo Nordisk's ziltivekimab also failed in a separate cardiovascular outcomes trial around the same time.

   Still unconfirmed

   • The failure may lead Novartis to deprioritize other antisense cardiovascular programs.
   • Some researchers speculate Lp(a) lowering might only work in primary prevention or specific genetic subgroups.

   What to watch next

   • Publication of full Lp(a)HORIZON dataset in a peer-reviewed journal
   • Results from other Lp(a)-lowering trials such as Amgen's olpasiran (OCEAN(a)-Outcomes)
   • Novartis pipeline update at next investor event regarding cardiovascular strategy
   Sources used for this update (11)

   1. www.statnews.com — STAT — Reporting from the frontiers of health and medicine
   2. NPR — A promising new medicine against heart disease fails unexpectedly
   3. CNN — Pelacarsen, a promising drug for an inherited heart risk, flops, stunning doctors
   4. The New York Times — How Cardiologists’ High Hopes for Two Drugs Were Dashed
   5. NBC News — The ‘slam dunk’ that wasn’t: Promising cholesterol drug fails to prevent heart attacks or stroke
   6. Reuters — Trial failures of Novartis, Novo Nordisk heart drugs leave experts guessing
   7. STAT — Failure of Novartis Lp(a) drug raises questions about cardiovascular strategy
   8. STAT — Why the latest heart drug failures should make us all more skeptical of AI hype
   9. Bloomberg — Novartis Abandons Heart Drug After Surprising Failure in Key Study
   10. TCTMD.com — Full Lp(a)HORIZON Results Affirm Lack of Pelacarsen Benefit in Secondary Prevention
   11. www.movefm.com.au — Heart drug trials disappoint Novartis and Novo Nordisk - Move FM News
   confidence 88%