Novo Nordisk's Experimental Heart Drug Misses Late-Stage Trial Goal, Raising Pressure To Diversify Beyond Obesity

Novo Nordisk has reported disappointing results from a late-stage clinical trial of its experimental cardiovascular drug, ziltivekimab, dealing a setback to the company's efforts to expand beyond its highly successful obesity and diabetes business. Following the announcement, shares of the Danish drugmaker fell 7.3% to 306.50 Danish crowns after the study showed the treatment failed to reduce the risk of major adverse cardiovascular events (MACE) compared with a placebo.

The Phase III study enrolled more than 6,300 patients with atherosclerotic cardiovascular disease, chronic kidney disease, and inflammation to evaluate whether a once-monthly injection of ziltivekimab, an IL-6-targeting therapy, could lower the risk of cardiovascular death, non-fatal heart attack, or non-fatal stroke. However, the drug failed to achieve the minimum 15% relative risk reduction in MACE that analysts considered necessary to support its regulatory approval and commercial potential.

The outcome represents a significant setback for Novo Nordisk, which acquired ziltivekimab through its $725 million acquisition of AstraZeneca spin-off Corvidia Therapeutics in 2020. At the time, the company expected the therapy to reach the market in the second half of the decade. Earlier clinical studies had generated optimism after the drug reduced a key marker of blood vessel inflammation by up to 92% without some of the safety concerns commonly associated with older anti-inflammatory treatments, such as increased cholesterol levels or fatal infection risks.

Analysts said the failed trial increases pressure on Novo Nordisk to strengthen its pipeline outside obesity and diabetes, which remain its primary growth drivers. Markus Manns, portfolio manager at Union Investment, a Novo shareholder, said the disappointing results reinforce the need for the company to diversify into other therapeutic areas. TD Cowen analysts described the findings as an unexpected setback that removes one of Novo's most promising cardiovascular assets, while BMO Capital Markets said the company may now need to pursue larger acquisitions or strategic deals in cardiovascular, metabolic, or rare diseases to restore investor confidence.

Novo Nordisk said the overall rates of side effects and serious adverse events were similar between patients receiving ziltivekimab and those given a placebo. However, serious infections occurred more frequently in the treatment group, a finding consistent with other IL-6-targeting therapies. The results also highlight the challenges of developing anti-inflammatory treatments for cardiovascular disease, following the FDA's rejection of Novartis' canakinumab in 2018 despite its ability to reduce cardiovascular events because it significantly increased the risk of fatal infections.

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