LONDON — After a recent spate of setbacks, Novo Nordisk has raised the curtain on data detailing semaglutide’s ability to cut the risk of heart failure and cardiovascular death in a late-phase test of type 2 diabetes patients with chronic kidney disease.
The results are important because Novo plans to resubmit the GLP-1 agonist for heart failure patients with obesity with these additional results from the Phase 3 FLOW trial, after it yanked its original FDA filing earlier this month.
The resubmission is part of Novo’s efforts to expand semaglutide’s use beyond diabetes and obesity with an eye to broader reimbursement. The company has already secured an FDA thumbs up for Wegovy — the version of the semaglutide used for weight loss — to reduce the risk of major adverse cardiovascular events in overweight or obese adults with established cardiovascular disease.
In the placebo-controlled FLOW study, patients given semaglutide saw a 27% relative risk reduction in composite heart failure events or cardiovascular death at median follow-up of around 40 months (p=0.0005), according to the results of a prespecified analysis presented to a packed room Friday at the European Society of Cardiology annual meeting in London. When the endpoint was split into separate parts, the patients saw a 27% relative risk reduction in heart failure events and a 29% relative risk reduction in cardiovascular events.
“The data itself is kind of resounding,” Ali Pashazadeh, founder of strategic advisory firm Treehill Partners, told Endpoints News in an interview, adding they would likely support approval and adoption of the drug. But Pashazadeh also said that the thought of using GLP-1s for many years — which is typical of heart medications — raises concerns because “that’s not what GLP-1s were designed to do.” He said he would like to see more data on the long-term safety profile of the drug class.
The FLOW trial set 1 mg semaglutide against placebo as an adjunct to standard of care in more than 3,500 people with type 2 diabetes and chronic kidney disease.
Topline data released in March showed the drug cut the risk of kidney disease progression and cardiovascular and kidney death by almost a quarter compared with placebo in the trial’s primary endpoint. In May, Novo reported success in key secondary endpoints, with semaglutide slashing the risk of major cardiovascular events by 18% and all-cause mortality by 20%.
Results from a separate semaglutide trial in adults with heart failure with preserved ejection fraction and obesity — called STEP HFpEF — formed the basis of an FDA filing for a label expansion for this population. But in August, Novo disclosed it had pulled its filing in a surprise move after discussions with the FDA, and said it will resubmit the application next year with more data, including from FLOW.
Just a few days before that, Eli Lilly reported that its GLP-1 tirzepatide slashed the risk of a heart failure urgent visit or hospitalization, oral diuretic intensification or cardiovascular death by 38% versus placebo in a Phase 3 trial in the same indication as STEP HFpEF.
Pashazadeh said it’s difficult to compare results between the Novo and Lilly studies because of slightly different patient characteristics, adding “it remains to be seen” which GLP-1 is more effective in terms of heart outcomes. “I do think we’re going to see slightly different efficacy between the GLP-1s in different contexts,” he added.
Novo has faced a number of challenges in recent months, including its second-quarter sales falling short of Wall Street expectations. Even so, in the US alone, its GLP-1 franchise pulled in 46 billion DKK ($6.7 billion) for diabetes for the first half of the year.
In July, the drugmaker also lost its case against the Inflation Reduction Act, although the company said it plans to appeal the decision. That same month, the FDA rejected Novo’s once-weekly insulin formulation, insulin icodec, because it had remaining questions about the manufacturing process for the treatment. The drugmaker said it doesn’t expect to be able to meet the regulator’s requests this year.
Eli Lilly, meanwhile, upped its 2024 revenue guidance on the back of the strong performance of its GLP-1 franchise.