--- title: "Novo Nordisk's ziltivekimab cut inflammation 76% but not heart outcomes; Novartis's pelacarsen failed too" description: "Published in the New England Journal of Medicine beside Novartis's identical pelacarsen null, the full results show how far a record biomarker win sits from a clinical outcome. The bill already runs from Novo's DKK 4.6 billion write-down to Ionis, down 28% on Monday." publisher: "The Inference" section: "Health" published: 2026-11-09T17:51:29.717Z modified: 2026-11-09T17:51:29.717Z canonical: https://theinference.org/article/novo-nordisk-s-ziltivekimab-cut-inflammation-76-but-not-heart-outcomes-novartis-s-pelacarsen-failed-too language: en keywords: "Novo Nordisk, Novartis, Ionis Pharmaceuticals, Clinical Trials, Pharma" --- # Novo Nordisk's ziltivekimab cut inflammation 76% but not heart outcomes; Novartis's pelacarsen failed too > Published in the New England Journal of Medicine beside Novartis's identical pelacarsen null, the full results show how far a record biomarker win sits from a clinical outcome. The bill already runs from Novo's DKK 4.6 billion write-down to Ionis, down 28% on Monday. [The full ZEUS results](https://newsroom.heart.org/news/researchers-say-inflammation-as-a-treatment-target-still-important-despite-neutral-results-of-zeus-trial), presented at the American Heart Association's Chicago sessions on Saturday and published the same day in the New England Journal of Medicine, settle what the field's biggest biomarker win was worth. [Novo Nordisk](https://theinference.org/markets/companies/novo-nordisk)'s ziltivekimab cut interleukin-6, an immune signaling protein, by 76% and high-sensitivity C-reactive protein, the standard blood measure of inflammation, by 64% across 6,376 patients [1][2]. Heart attacks, strokes and cardiovascular deaths landed where placebo left them: 561 events against 565, a hazard ratio of 0.99 [1][2]. [Novartis's](https://theinference.org/markets/companies/novartis) pelacarsen matched the pattern at a second target, in the same journal the same day: lipoprotein(a), an inherited cholesterol-like particle, fell 78% across 8,323 patients with no change in any cardiovascular outcome [3]. Ionis Pharmaceuticals, which discovered pelacarsen and licensed it to Novartis, had its partner's [topline null on the record from September 4](https://ir.ionis.com/investor-news/press-releases) [4]. The biomarkers fell by record margins in both trials; the event rate did not move in either. *Chart: **Record biomarker cuts, a flat line on heart attacks and strokes** Bar chart of reductions versus placebo: IL-6 down 76 percent, hs-CRP down 64 percent, lipoprotein(a) down 78 percent, and cardiovascular events down about 1 percent.* *Percent reduction versus placebo. ZEUS: 6,376 patients, biomarker changes at 24 months, events over median 33-month follow-up (17.6% vs 17.7%, hazard ratio 0.99). Lp(a)HORIZON: 8,323 patients, mean Lp(a) reduction. Sources: AHA Newsroom, TCTMD, MedPage Today. [1][2][3]* ## The drugs changed the blood, not the patient The null was priced before the weekend. [Novo](https://theinference.org/markets/companies/novo-nordisk) announced [the ZEUS topline](https://www.tctmd.com/news/zeus-what-went-awry-ziltivekimab-inflammation-and-what-now) in August [2]; the September futility halts of its companion HERMES and ATHENA trials followed [5]; Saturday supplied the full detail and the cost. Serious infections ran at 20.4% on the drug against 17.9% on placebo, and blood clots at 1.6% against 0.6% [5]. Deaths came to 538 on ziltivekimab against 542 on placebo, about 17% of those enrolled [1]. *Chart: **Infections ran 2.5 points higher and clots nearly tripled on ziltivekimab** Column chart comparing serious infections, 20.4 percent on ziltivekimab versus 17.9 percent on placebo, and blood clots, 1.6 percent versus 0.6 percent, in the ZEUS trial.* *Share of ZEUS patients with the event over median 33 months of follow-up, ziltivekimab versus placebo. Sources: Tech Times. [5]* Participants averaged 69 years old, with both cardiovascular disease and chronic kidney disease [2]. Lead investigator Paul Ridker of Mass General Brigham allowed that disease this advanced may have been "too little, too late" to modify [1]. ## The genetics priced a lifetime; the trial tested two and a half years Both programs were built on Mendelian randomization, a method that uses inherited gene variants to estimate what a lifetime of lower exposure to a target does to risk [5]. A trial instead suppresses the marker for about two and a half years in people who already have arterial plaque. ZEUS confirmed both halves of that distinction: patients who started with more inflammation had more events, and lowering it prevented none [6]. "Genetic causality is not therapeutic reversibility," Ridker said. "Both the Mendelian randomization and the clinical trials are correct" [6]. Trial discussant Priscilla Hsue of UC San Francisco named the other suspect: the drug blocks the IL-6 protein itself, and the strongest human genetic evidence points at its receptor [5][6]. ## The write-down is booked; the spending is not Novo bought the antibody in 2020 from Corvidia Therapeutics, the AstraZeneca spinoff that developed it, for $725 million upfront and up to $2.1 billion with milestones [5]. [Its third-quarter report](https://finance.yahoo.com/healthcare/articles/novo-raises-full-outlook-continued-063000545.html) then booked DKK 8.7 billion of impairments, DKK 4.6 billion of them on ziltivekimab [7]. That is the gap between the 27% rise in adjusted operating profit and the 9% fall in reported profit [we covered on November 5](https://theinference.org/article/novo-nordisk-s-27-profit-jump-is-the-adjusted-number-the-reported-number-fell-9) [7]. NVO closed Friday at $40.31, with price-to-sales and price-to-earnings ratios near half their five-year averages and a 4.46% dividend yield [8]. At that price the investment case rests on the Wegovy pill's launch, not on this pipeline [8]. *Chart: **Operating income has fallen year over year in three of the last four quarters** Column chart of Novo Nordisk quarterly operating income in billions of US dollars, from 3.7 billion in Q2 2024 to a peak of 9.1 billion in Q1 2026 and 3.5 billion in Q3 2026.* *Quarterly operating income in US dollars from Novo Nordisk's SEC filings. Q3 2026 includes DKK 8.7 billion of impairments, DKK 4.6 billion of them on ziltivekimab. Source: Novo Nordisk quarterly filings, retrieved 9 November 2026. [11]* ## The same null reprices Novartis, Ionis and the next readouts Novartis has stopped pelacarsen in atherosclerotic disease, keeping only a study in calcific aortic valve stenosis; its Swiss shares rose 0.3% Monday [10]. Ionis, which licensed the drug to Novartis in 2019 for $150 million upfront, fell 28% on the data and [its own lowered guidance](https://www.msn.com/en-us/money/other/a-failed-trial-for-a-heart-drug-casts-shadow-over-rivals-developing-similar-therapies/ar-AA2h4EFR) [9][10]. Evan Seigerman, an analyst at BMO Capital Markets, told investors the odds of a clear benefit for the two rival Lp(a) programs are "extremely low" [10]. ## ARTEMIS continues; Novo still owes Ventus up to $700 million The watch list from here is concrete. ARTEMIS, testing the same antibody in acute coronary ischemia, "has been allowed to continue," Ridker said, "so we're optimistic on that" [6]. Novo [owes up to $700 million more to Ventus Therapeutics](https://theinference.org/article/days-after-an-8-selloff-novo-pays-a-microcap-up-to-1-3b-to-make-its-shots-monthly), the drugmaker behind an NLRP3 inhibitor one step upstream of IL-6, on a cascade whose causal point of intervention Ridker calls uncertain [2][5]. And the next two readouts, [Amgen's](https://theinference.org/markets/companies/amgen) olpasiran and [Eli Lilly's](https://theinference.org/markets/companies/eli-lilly) lepodisiran, arrive with analysts expecting $2.3 billion in peak olpasiran sales [10]. If they null as well, that expectation is the next thing repriced. ## Takeaway Ziltivekimab and pelacarsen cut IL-6, hs-CRP and Lp(a) by 64% to 78% and changed no cardiovascular outcomes; ARTEMIS, olpasiran and lepodisiran are the next tests of whether the biology pays off in events. ## Sources 1. [American Heart Association Newsroom, "Researchers say inflammation as a treatment target still important despite neutral results of ZEUS trial," 7 November 2026](https://newsroom.heart.org/news/researchers-say-inflammation-as-a-treatment-target-still-important-despite-neutral-results-of-zeus-trial) 2. [TCTMD, Caitlin E. Cox, "ZEUS: What Went Awry With Ziltivekimab in Inflammation, and What Now?", 7 November 2026](https://www.tctmd.com/news/zeus-what-went-awry-ziltivekimab-inflammation-and-what-now) 3. [American Heart Association Newsroom, "Lp(a) HORIZON trial: Lp(a) fell by 78%, but cardiovascular outcomes unexpectedly neutral," 7 November 2026](https://newsroom.heart.org/news/lp-a-horizon-trial-lp-a-fell-by-78-but-cardiovascular-outcomes-unexpectedly-neutral) 4. [Ionis Pharmaceuticals investor news, "Ionis partner Novartis announces Lp(a)HORIZON Phase 3 topline results for pelacarsen," 4 September 2026](https://ir.ionis.com/investor-news/press-releases) 5. [Tech Times, "Novo Nordisk ZEUS Trial Cut Inflammation 76%; Zero Reduction in Heart Attacks Across 6,376 Patients," 8 November 2026](https://www.techtimes.com/articles/330262/20261108/novo-nordisk-zeus-trial-cut-inflammation-76-zero-reduction-heart-attacks-across-6376-patients.htm) 6. [MedPage Today, Susan Jeffrey, "Ziltivekimab falls short for cutting cardiovascular events in ASCVD, CKD," 7 November 2026](https://www.msn.com/en-us/news/other/ziltivekimab-falls-short-for-cutting-cardiovascular-events-in-ascvd-ckd/ar-AA2gZa18) 7. [Novo Nordisk company announcement No 65/2026, Q3 2026 financial report, via Yahoo Finance, 4 November 2026](https://finance.yahoo.com/healthcare/articles/novo-raises-full-outlook-continued-063000545.html) 8. [NAI500, "Novo Nordisk's 2026 Transition Year: Early Wegovy Pill Success Meets Weak Earnings and a Stock Down 20% Over Five Years," November 2026](https://nai500.com/blog/2026/11/novo-nordisks-2026-transition-year-early-wegovy-pill-success-meets-weak-earnings-and-a-stock-down-20-over-five-years/) 9. [pharmaphorum, Phil Taylor, "Novartis' pelacarsen fail raises questions for other drugs," 9 November 2026](https://pharmaphorum.com/news/novartis-pelacarsen-fail-raises-questions-other-drugs) 10. [MarketWatch, Jaimy Lee, "A failed trial for a heart drug casts shadow over rivals developing similar therapies," 9 November 2026](https://www.msn.com/en-us/money/other/a-failed-trial-for-a-heart-drug-casts-shadow-over-rivals-developing-similar-therapies/ar-AA2h4EFR) 11. [Novo Nordisk, quarterly figures from its SEC filings, retrieved 9 November 2026](https://www.sec.gov/cgi-bin/browse-edgar?action=getcompany&CIK=0000353278) --- Novo Nordisk's ziltivekimab cut inflammation 76% but not heart outcomes; Novartis's pelacarsen failed too — The Inference. Canonical: https://theinference.org/article/novo-nordisk-s-ziltivekimab-cut-inflammation-76-but-not-heart-outcomes-novartis-s-pelacarsen-failed-too