Did Novo’s phase 3 flop kill the inflammation hypothesis in heart disease?
Kelly Bilodeau
Mon, August 10, 2026 at 2:51 PM GMT+5:30
3 min read
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When Novo Nordisk recently reported that its experimental heart drug ziltivekimab failed to reduce the risk of heart attacks and strokes in a late-stage trial, the market reaction was swift. Novo’s stock fell as much as 10%, while shares of several other companies also tumbled amid fears the results cast doubt on whether targeting inflammation could reduce the risk of serious cardiovascular events
The phase 3 Zeus trial enrolled over 6,300 people with atherosclerotic cardiovascular disease, chronic kidney disease and inflammation, following participants for up to four years. Although ziltivekimab produced the expected biological effect, lowering interleukin-6 and high-sensitivity C-reactive protein (hsCRP), it failed to reduce major adverse cardiovascular events (MACE) — cardiovascular death, nonfatal heart attack or stroke — compared with placebo
While investors may have been spooked by the failure, it didn’t necessarily mark a death knell for the inflammation hypothesis he said, the result may say more about IL-6 inhibition (and hsCRP as a surrogate marker) than it does about inflammation itself
“In our view, the bearish read-through is more limited to hsCRP’s surrogacy for cardio protection in the context of IL-6 inhibition,” he said in an email
The better approach to reducing cardiovascular events might involve targeting a different protein, interleukin-1beta (IL-1β). In Novartis’ Cantos trial, for instance, a 150-mg dose of the drugmaker’s IL-1β inhibitor Ilaris significantly reduced recurrent cardiovascular events compared with placebo
“We have validation that IL-1beta inhibition leads to MACE reduction,” Hsieh said. “This effect was dependent on hsCRP reduction magnitude (2 mg/L cutoff). So I wouldn’t say the data invalidates the inflammatory hypothesis in its entirety.”
The Novo readout’s ripple effect
While the inflammation hypothesis may not be dead, Novo’s phase 3 results could dampen enthusiasm for NLRP3 inhibitors, a broader anti-inflammatory approach that can also affect IL-6 expression. For instance, BioAge Labs’ shares fell roughly 60% in premarket trading after Novo’s Zeus readout, according to the William Blair note
BioAge is testing BGE-102 in the phase 2 Quell-Cv trial in patients at elevated cardiovascular risk and plans a phase 1b/2a study in diabetic macular edema
