Novo Nordisk's Late-Stage Cardiovascular Drug Fails Key Trial, Shares Drop

Novo Nordisk has reported disappointing results from a late-stage clinical trial of its experimental cardiovascular drug, ziltivekimab, marking a setback in the company's efforts to expand beyond its blockbuster obesity and diabetes medicines. Following the announcement, the Danish drugmaker's shares fell 7.3% to 306.50 Danish crowns as investors reacted to the failed study.

The Phase III trial found that ziltivekimab did not significantly reduce the risk of major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal heart attack, and non-fatal stroke, compared with a placebo. The study enrolled more than 6,300 patients with atherosclerotic cardiovascular disease, chronic kidney disease, and inflammation to determine whether a once-monthly injection of the IL-6-targeting therapy could lower cardiovascular risk. However, the drug failed to achieve the minimum 15% relative risk reduction in MACE that analysts had expected.

The outcome is a major setback for Novo Nordisk, which acquired ziltivekimab through its $725 million purchase of Corvidia Therapeutics, an AstraZeneca spin-off, in 2020. At the time of the acquisition, the company expected the treatment to reach the market in the second half of the decade. Earlier clinical studies had shown encouraging results, with ziltivekimab reducing a key marker of blood vessel inflammation by up to 92% while avoiding some of the serious side effects associated with older anti-inflammatory therapies.

Industry analysts said the failed trial increases pressure on Novo Nordisk to diversify its pipeline beyond obesity and diabetes, two areas that currently drive most of the company's growth. Markus Manns, portfolio manager at Novo shareholder Union Investment, said the disappointing result highlights the need for the company to expand into other disease areas. 

Analysts at TD Cowen described the findings as an unexpected setback that removes one of Novo's most promising opportunities in cardiovascular disease, while BMO Capital Markets suggested the company may now face greater pressure to pursue acquisitions or strategic deals, particularly in cardiovascular, metabolic, or rare diseases, to restore investor confidence.

In terms of safety, Novo Nordisk said the overall rates of side effects and serious adverse events were similar between the ziltivekimab and placebo groups. However, serious infections occurred more frequently in patients receiving ziltivekimab, a finding that is consistent with other IL-6-targeting therapies. The results also revive concerns surrounding anti-inflammatory cardiovascular treatments, following the FDA's 2018 rejection of Novartis' canakinumab after the drug showed cardiovascular benefits but significantly increased the risk of fatal infections.

Despite the failed trial, Novo Nordisk said the outcome will not affect its adjusted operating profit outlook for 2026, although it expects to record a non-cash impairment charge in the third quarter. The company will continue two ongoing late-stage studies evaluating ziltivekimab in patients with heart failure and in those recovering from an acute heart attack, with results expected in the first half of 2027. However, BMO Capital Markets analysts said they now consider positive outcomes from these remaining trials to be highly unlikely.