Novo reveals semaglutide’s cardiac outcomes in Phase 3 for resubmission

LONDON — Novo Nordisk has unveiled promising data on semaglutide's potential to reduce heart failure and cardiovascular death risks in type 2 diabetes patients with chronic kidney disease. This revelation follows a series of setbacks for the company, which plans to resubmit semaglutide to the FDA for heart failure patients with obesity, leveraging these new results from the Phase 3 FLOW trial.

Novo Nordisk's objective is to expand semaglutide's applications beyond diabetes and obesity, aiming for broader reimbursement. The company has already achieved FDA approval for Wegovy, the weight loss variant of semaglutide, to lower the risk of major adverse cardiovascular events in overweight or obese adults with established cardiovascular disease.

In the placebo-controlled FLOW study, semaglutide demonstrated a 27% relative risk reduction in composite heart failure events or cardiovascular death over a median follow-up period of approximately 40 months. When analyzing the endpoint components separately, there was a 27% relative risk reduction in heart failure events and a 29% reduction in cardiovascular events.

Ali Pashazadeh, founder of Treehill Partners, emphasized the significance of the data, predicting it would support the drug's approval and adoption. However, he noted concerns over the long-term use of GLP-1s for heart conditions, as these drugs were not originally designed for such uses, and called for more data on their long-term safety profiles.

The FLOW trial compared 1 mg semaglutide to a placebo as an addition to standard care in over 3,500 individuals with type 2 diabetes and chronic kidney disease. Initial data released in March indicated that semaglutide reduced the risk of kidney disease progression and cardiovascular and kidney death by nearly 25% compared to placebo. In May, Novo Nordisk announced that semaglutide also met key secondary endpoints, reducing the risk of major cardiovascular events by 18% and all-cause mortality by 20%.

In a separate study, the STEP HFpEF trial, semaglutide was tested in adults with heart failure with preserved ejection fraction and obesity. This formed the basis for an FDA label expansion filing for this population. However, in August, Novo Nordisk unexpectedly withdrew its filing after discussions with the FDA, opting to resubmit next year with additional data, including results from the FLOW trial.

Concurrent to these developments, Eli Lilly reported that its GLP-1 drug, tirzepatide, achieved a 38% reduction in the risk of heart failure urgent visits, hospitalizations, oral diuretic intensification, or cardiovascular death compared to placebo in a Phase 3 trial targeting the same condition as the STEP HFpEF study.

Pashazadeh pointed out the challenges in comparing the Novo Nordisk and Eli Lilly studies due to differences in patient characteristics. He suggested that the efficacy of GLP-1s might vary across different contexts and patient populations.

Novo Nordisk has faced various challenges recently, including second-quarter sales not meeting Wall Street expectations. Despite this, its GLP-1 franchise generated $6.7 billion in the US for diabetes in the first half of the year. In July, the company lost a legal case against the Inflation Reduction Act, with plans to appeal. That same month, the FDA rejected Novo’s once-weekly insulin formulation, insulin icodec, due to unresolved questions about its manufacturing process. Novo does not expect to resolve these regulatory concerns this year.

Eli Lilly, meanwhile, increased its 2024 revenue forecast, buoyed by the strong performance of its GLP-1 franchise.

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