Novartis and Novo Nordisk cardiovascular drug trials fail in 2026

Two experimental cardiovascular drugs developed by Novartis and Novo Nordisk have failed to demonstrate a reduction in major heart-related events in late-stage clinical trials, despite significantly lowering their intended biological targets.

Results presented at the American Heart Association (AHA) Scientific Sessions in Chicago on 7 November showed that Novartis’ pelacarsen reduced levels of lipoprotein(a), or Lp(a), by approximately 78%, but did not prevent further cardiovascular events. Novo Nordisk’s ziltivekimab also lowered inflammation markers substantially without reducing the risk of heart attacks, strokes or cardiovascular death.

The findings represent setbacks for two different approaches to cardiovascular treatment and raise questions about whether improvements in specific biological markers will necessarily translate into better patient outcomes.

Both studies were published in the New England Journal of Medicine alongside their presentation at the AHA meeting.

Novartis pelacarsen trial fails to reduce cardiovascular events

Novartis’ Phase III Lp(a)HORIZON trial evaluated pelacarsen, an investigational antisense oligonucleotide designed to reduce the production of lipoprotein(a).

Elevated Lp(a) is an inherited cardiovascular risk factor associated with an increased likelihood of heart disease and stroke. It is estimated to affect approximately one in five people worldwide, and there are currently no approved medicines specifically targeting elevated Lp(a).

The trial enrolled 8,350 patients with established cardiovascular disease and elevated Lp(a) levels. Participants received either monthly pelacarsen injections or a placebo and were followed for a median of 4.7 years.

Pelacarsen achieved a substantial reduction in Lp(a) levels. However, this did not translate into a lower incidence of major adverse cardiovascular events.

In the efficacy analysis, the primary endpoint occurred in 12.3% of patients receiving pelacarsen, compared with 12.1% in the placebo group. The difference was not statistically significant.

The primary endpoint included cardiovascular death, non-fatal heart attacks, non-fatal strokes and urgent coronary revascularisation procedures.

The findings were disappointing for a treatment designed to address an inherited cardiovascular risk factor that has remained without a specifically approved targeted therapy.

Novartis had announced in September that the trial failed to meet its primary endpoint. The detailed results have now provided further evidence that reducing Lp(a) alone did not improve cardiovascular outcomes in the population studied.

Novo Nordisk’s ziltivekimab misses its primary endpoint

A separate Phase III study also failed to establish a cardiovascular benefit for Novo Nordisk’s experimental drug ziltivekimab.

The ZEUS trial investigated whether inhibiting interleukin-6 (IL-6), a protein involved in inflammation, could reduce cardiovascular complications among high-risk patients.

The study included 6,376 people with established atherosclerotic cardiovascular disease, chronic kidney disease and elevated inflammation.

Participants received either a monthly 15 mg injection of ziltivekimab or a placebo. The median follow-up period was 33 months.

Ziltivekimab successfully reduced inflammatory markers. At 24 months, levels of free IL-6 and high-sensitivity C-reactive protein were substantially lower in the treatment group than in the placebo group.

However, the treatment did not reduce the incidence of the trial’s primary cardiovascular endpoint.

Major cardiovascular events occurred in 17.6% of patients receiving ziltivekimab and 17.7% of those receiving placebo. The difference was not statistically significant.

The results indicate that inhibiting the IL-6 inflammatory pathway did not produce a measurable reduction in cardiovascular events among the high-risk population enrolled in the study.

Novo Nordisk had announced the unsuccessful headline results in July 2026.

Why the two clinical trial failures matter

The studies investigated different biological mechanisms but produced a similar outcome: the experimental medicines successfully affected their intended targets without demonstrating corresponding improvements in cardiovascular health.

Pelacarsen was designed to lower Lp(a), while ziltivekimab targeted inflammation through the IL-6 pathway.

The results therefore raise important questions about the relationship between biological markers and clinical outcomes in cardiovascular drug development.

In the pelacarsen study, researchers are still considering whether the patient population, treatment duration or differences between drug technologies could have influenced the outcome.

Some researchers have pointed out that the trial focused on people who had already experienced a major cardiovascular event. Other experimental Lp(a)-lowering treatments are being evaluated in different patient populations.

Similarly, researchers involved in the inflammation research have raised the possibility that intervention may have occurred too late in patients with advanced cardiovascular and kidney disease.

These explanations remain areas for further investigation rather than established reasons for the trial failures.

Amgen and Eli Lilly continue developing Lp(a)-lowering treatments

The Novartis result also has implications for other pharmaceutical companies developing medicines targeting elevated Lp(a).

Amgen and Eli Lilly are advancing different RNA-based approaches designed to reduce Lp(a) production.

Amgen’s olpasiran and Eli Lilly’s lepodisiran have demonstrated substantial reductions in Lp(a) levels in clinical studies. However, whether those reductions will translate into fewer cardiovascular events remains to be established through outcomes trials.

The distinction between the treatment technologies and the patient populations being studied will be important when interpreting future results.

According to the research timeline reported alongside the November findings, Amgen’s Phase III results are expected in early 2028, while Eli Lilly’s are expected in 2029.

Those studies could provide further evidence about whether lowering Lp(a) can reduce cardiovascular risk and whether different therapeutic approaches produce different clinical outcomes.

Pharmaceutical companies face further questions over cardiovascular drug development

The two trial outcomes highlight a broader challenge for pharmaceutical research: demonstrating that a drug’s biological activity translates into meaningful clinical benefits.

For companies developing cardiovascular medicines, successful target engagement is an important part of clinical development, but it is not sufficient to establish therapeutic effectiveness.

The results also reinforce the importance of patient selection, disease progression and the design of clinical outcomes studies.

For Novartis and Novo Nordisk, the findings represent setbacks for two experimental cardiovascular treatments. However, they do not establish that Lp(a) or inflammation are irrelevant to cardiovascular disease.

Researchers have called for further studies involving different compounds, therapeutic strategies and patient populations.

The next important developments will come from ongoing Lp(a)-lowering programmes and further research into inflammation-related cardiovascular treatments. These studies will help determine whether alternative approaches can convert improvements in biological markers into measurable reductions in heart attacks, strokes and cardiovascular deaths.

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