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Novartis and Ionis’ Pelacarsen Lowers Lp(a) but Misses on Cardiovascular Outcomes

Pelacarsen cut Lp(a) yet failed to reduce cardiovascular events in 8,323 patients, throwing the entire Lp(a)-lowering thesis into doubt; the same day, Novo Nordisk scrapped two more Phase 3 ziltivekimab heart-failure trials.
pharminent September 7, 2026 (Last updated: September 7, 2026)

STRATEGIC NEWS WATCH — September 7, 2026

Pelacarsen cut Lp(a) yet failed to reduce cardiovascular events in 8,323 patients, throwing the entire Lp(a)-lowering thesis — not one molecule — into doubt; in a second blow to a late-stage cardiovascular program, Novo Nordisk scrapped two more Phase 3 heart-failure trials of ziltivekimab after its monitoring committee saw little chance of bettering the already-failed ZEUS trial.

Today’s top developments:

  • Novartis and Ionis’ pelacarsen lowered Lp(a) but missed the primary cardiovascular endpoint in the 8,323-patient Phase 3 Lp(a)HORIZON trial, a result that tests the emerging Lp(a) class rather than one asset (BioPharma Dive)
  • Novo Nordisk discontinued the HERMES (4,900 patients) and ATHENA (673 patients) Phase 3 heart-failure trials of ziltivekimab after a monitoring committee judged a different outcome from the missed ZEUS trial unlikely (Fierce Biotech)
  • In Novo Nordisk’s Phase 3 STEP Young trial, 40.4% of children aged 6 to 11 on semaglutide plus lifestyle modification no longer met obesity criteria at week 68, versus 0% on placebo (Reuters)
  • The FDA granted Ionis’ Zanvastro (zilganersen) a traditional approval as the first disease-modifying treatment for Alexander disease, anchoring the company’s rare-neurology pipeline (Fierce Biotech)
  • Roche began screening in Europe for PrevenTRON, a Phase 3 trial enrolling roughly 1,600 cognitively unimpaired adults to test trontinemab in Alzheimer’s prevention using plasma p-tau217 screening (Pharmaphorum)

What to Watch

  • Lp(a)HORIZON subgroups by depth of lowering — Pelacarsen achieved Lp(a) reduction and still missed the composite endpoint, so the only question that matters for Amgen’s olpasiran and Eli Lilly’s lepodisiran is whether benefit scales with the magnitude of reduction. Watch for the baseline-Lp(a) and percentage-reduction subgroup analyses when the full data are presented; Novartis has not yet named the congress or a date.
  • ARTEMIS is now the whole ziltivekimab thesis — With HERMES and ATHENA discontinued and ZEUS missed, the post-myocardial-infarction trial is the only remaining late-stage read on the IL-6 hypothesis, and the discontinuations point to a futility judgement on the mechanism rather than a fixable safety issue. Readout is expected in the first half of 2027.
  • STEP Young’s 104-week data and a filing date — The 68-week primary result is in; the supportive 104-week endpoints and full dataset are due at ObesityWeek 2026 in Washington, DC, November 14-17. Novo has announced no regulatory filing date for the 6-to-11 age group, and duration of treatment, not effect size, is the question a pediatric label will turn on.
  • Zanvastro’s $285,000-per-dose price sets the pipeline template — Ionis priced Zanvastro at $285,000 per dose — roughly $1.14 million a year at the approved quarterly dosing — with availability described as “in the coming weeks” from September 3 and peak sales guided above $100 million. In a disorder affecting fewer than 1,000 US patients, that number sets the reimbursement template for the rest of Ionis’ neurology pipeline — most immediately obudanersen for Angelman syndrome, whose late-stage data are due in the second half of 2027.
  • PrevenTRON enrolment throughput — A 1,600-patient prevention trial screening on plasma p-tau217 is a test of the biomarker’s operational viability as much as of trontinemab. Watch enrolment pace and site expansion beyond the lead UK site; a time-to-progression endpoint in asymptomatic people needs years of follow-up, and no readout date has been announced.

This brief highlights the edition’s top stories. Read the full September 7, 2026 edition → for all stories and analysis — or browse the Strategic News Watch archive.

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