▎WuXiEdited by Kant Content Team

Recently, Novo Nordisk announced the results of the Phase 3 trial STEP HFpEF DM at the 2024 American College of Cardiology (ACC). The analysis showed that, compared with placebo, once-weekly subcutaneous injection of its weight-loss therapy Wegovy (semaglutide) significantly reduced heart failure-related symptoms and physical limitations while improving exercise function in obese heart failure patients with preserved ejection fraction (HFpEF) who also have type 2 diabetes (T2D). The trial results were simultaneously published in The New England Journal of Medicine. According to the industry media STAT,Novo Nordisk submitted the results of this trial earlier this year, along with the findings from a previous Phase 3 clinical trial on Wegovy for the treatment of HFpEF patients, to the U.S. FDA in hopes of obtaining approval for the expanded indication of the drug to treat HFpEF.

HFpEF Accounts for About Half of All Heart Failure CasesCurrently, there are no approved therapies for the treatment of obese HFpEF patients with type 2 diabetes.

STEP HFpEF DM is a Phase 3 randomized trial primarily aimed at investigating the effects of once-weekly subcutaneous administration of 2.4 mg Wegovy compared to placebo on symptoms, physical function, and weight in patients with T2M HFpEF obesity (BMI ≥ 30 kg/m²). The trial enrolled a total of 616 patients.CommonThe primary endpoint was the change in patients' weight and the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) from baseline to Week 52.KCCQ-CSS scores are used to measure symptoms and physical limitations in HFpEF patients, ranging from 0 to 100, with higher scores indicating fewer symptoms and physical limitations.The confirmatory secondary endpoints included changes in the 6-minute walk distance (6MWD), etc.

▲Summary of Efficacy Results from the STEP HFpEF DM Trial (Image Source: Reference [1])

Analysis shows that the trial met dual primary endpoints.The mean change in KCCQ-CSS was 13.7 points for patients in the Wegovy group and 6.4 points for those in the placebo group (estimated difference, 7.3 points; 95% CI: 4.1 to 10.4; P<0.001)., showing that Wegovy can significantly improveT2M HFpEF ObesityThe patient's symptoms and physical limitations.The percentage change in body weight was -9.8% in the Wegovy group and -3.4% in the placebo group (estimated difference, -6.4 percentage points; 95% CI: -7.6 to -5.2; P<0.001).Results for the confirmatory secondary endpoint also showed Wegovy superior to placebo, with an estimated between-group difference in 6MWD of 14.3 meters (95% CI: 3.7 to 24.9; P=0.008).

▲STEP HFpEF DM Trial Meets Dual Primary Endpoints (Image Source: Reference [1])

In addition, the analysis also showsWegovy May Reduce the Rate of Hospitalization or Emergency Visits for Heart Failure Patients, 2.3% of patients using Wegovy experienced this, compared to 5.9% in the placebo group (HR=0.40; 95% CI: 0.15 to 0.92).

In terms of safety, 55 subjects (17.7%) in the Wegovy group reported serious adverse events, while 88 subjects (28.8%) in the placebo group reported serious adverse events. Cardiac disorders were reported in 6.1% of patients in the Wegovy group and 13.1% in the placebo group.

▲Safety Results of the STEP HFpEF DM Trial (Image Source: Reference [1])

Novo Nordisk in August last year in The New England Journal of MedicinePublishWegovy for the Treatment of Obese HFpEF Patients (without T2M) STEPHFpEFPhase 3 Clinical TrialThe results. Compared with the trial announced this time, Wegovy showed consistent performance on the primary endpoint KCCQ-CSS score, with an estimated treatment difference of 7.8 points compared to placebo (p<0.001). Notably, in this trial, patients did not lose much weight, only 6.4 percentage points more than the placebo group. This is about 40% less than the weight loss observed in the STEP HFpEF trial, but the degree of heart failure benefit was similar in both studies.This shows that the benefits of Wegovy for HFpEF patients may not be entirely due to weight loss and may also involve other mechanisms, such as a direct impact on the heart.

This "Strongly suggests that weight loss is not the only mechanism in Wegovy's treatment of HFpEF, otherwise you would expect less weight loss and reduced benefits for heart failure. But that’s not what we observed."The chief investigator of the trial, Dr. Mikhail Kosiborod, stated.

WegovyIs a GLP-1 receptor agonist，It can stimulate insulin production, inhibit glucagon secretion, and reduce appetite and food intake.June 2021 FDAApprovalIt is used to treat ordinary obese patients. It is the first new drug approved by the US FDA for controlling ordinary obesity or overweight since 2014. The drugAnd later that same year, it received EU approval for the treatment of obesity indications.. Last month,Wegovy Again ObtainsFDA Approval, used to reduce the risk of cardiovascular death, heart attacks, and strokes in adults with cardiovascular disease and obesity or overweight.

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