How Cardiologists’ High Hopes for Two Drugs Were Dashed

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1. 10m ago

   Novartis Pelacarsen Trial Fails to Cut Heart Events Despite Lowering Lp(a)

   Novartis announced that its Phase 3 HORIZON trial of pelacarsen failed to reduce major cardiovascular events even though the drug successfully lowered lipoprotein(a) levels. The Cleveland Clinic-led study tested the antisense oligonucleotide in patients with elevated Lp(a) and established cardiovascular disease. Results stunned cardiologists who had viewed Lp(a) reduction as a promising therapeutic target. The failure casts doubt on similar programs in development at Amgen and Eli Lilly. Pelacarsen had been considered a potential breakthrough for an inherited risk factor affecting roughly one in five people globally.

   Why it matters

   Lipoprotein(a) is a genetically determined particle that promotes atherosclerosis and clotting, and until now no therapy could specifically lower it. Pelacarsen was the furthest advanced candidate designed to do so, making the trial a bellwether for the entire Lp(a) field. The negative outcome forces a re-evaluation of whether lowering Lp(a) alone translates into clinical benefit, or whether intervention must occur earlier or in different populations.

   What is confirmed

   • Novartis' Phase 3 HORIZON trial of pelacarsen failed to reduce major cardiovascular events.
   • The drug successfully lowered lipoprotein(a) levels in the trial.
   • The trial was led by the Cleveland Clinic and enrolled patients with elevated Lp(a) and established cardiovascular disease.
   • The failure affects confidence in similar Lp(a)-lowering programs at Amgen and Eli Lilly.

   Still unconfirmed

   • Experts are questioning whether Lp(a) reduction must start earlier in life to prevent events.
   • Some investigators suggest the trial population may have been too advanced for benefit.

   What to watch next

   • Detailed HORIZON data presentation at a major cardiology conference
   • Amgen and Eli Lilly updates on their Lp(a) programs
   • Regulatory feedback on the future of Lp(a) as a drug target
   Sources used for this update (9)

   1. www.nytimes.com — The New York Times - Breaking News, US News, World News and Videos
   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. Fierce Biotech — Novartis’ Lp(a) drug shows zero benefit, casting shadow over Amgen and Lilly programs
   7. Reuters — Trial failures of Novartis, Novo Nordisk heart drugs leave experts guessing
   8. Cleveland.com — Cleveland Clinic-led trial finds drug lowered lipoprotein(a), but did not reduce major heart events
   9. medicalxpress.com — Single-pill combination helps more patients control hypertension
   confidence 90%