Results from the phase III STEP HFpEF trial showing that compared with placebo, once-weekly semaglutide 2.4 mg led to large reductions in heart failure-related symptoms.- Novo Nordisk

HFpEF comprises roughly half of all heart failure cases and is associated with a high burden of symptoms and physical limitations affecting daily life, including fatigue, shortness of breath, reduced ability to exercise, and swelling of extremities. The majority (80%) of people with HFpEF also live with overweight or obesity, which is linked to a higher burden of symptoms, worse physical function and lower quality of life.

The findings, presented at the European Society of Cardiology (ESC) Congress in Amsterdam, Netherlands and published simultaneously in the New England Journal of Medicine, show large improvement in patient-reported Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), measuring the symptoms and physical limitations of HFpEF.

“As clinicians, we have limited treatment options to offer our patients living with HFpEF and obesity. Yet this is a condition that seriously impacts patients’ day-to-day experience, due to debilitating symptoms and functional limitations,” said Dr Mikhail Kosiborod, lead study investigator and cardiologist at Saint Luke’s Mid America Heart Institute, Kansas City, USA. “Today’s news heralds a possible fundamental paradigm shift in how cardiologists approach HFpEF in people with obesity. It’s gratifying to be able to share important evidence that has a potential to change the future clinical management of this vulnerable patient population.”

The mean change in the KCCQ-CSS was a 16.6-point increase at 52 weeks with semaglutide 2.4 mg vs 8.7 points with placebo, leading to an estimated treatment difference of 7.8 points (p<0.001). mean change in body weight was 13.3% reduction with semaglutide 2.4 mg vs. 2.6% reduction with placebo, leading to an estimated treatment difference of 10.7% weight reduction (p><0.001).></0.001).></0.001).>

STEP HFpEF also demonstrated a mean increase in 6-Minute Walking Distance (6MWD) of 21.5 metres at 52 weeks with semaglutide vs. 1.2 metres with placebo leading to an estimated treatment difference of 20.3 meters (p<0.001).1 semaglutide also reduced inflammation, as measured by high-sensitivity c-reactive protein (hscrp). the safety profile of semaglutide 2.4 mg was consistent with previous studies; fewer serious adverse events were observed with semaglutide 2.4 mg compared with placebo.></0.001).1>

About STEP HFpEF and STEP HFpEF-DM ; The primary objective of STEP HFpEF trial was to investigate the effects of semaglutide 2.4 mg subcutaneous once-weekly on symptoms, physical function, and body weight compared with placebo in patients with HFpEF and obesity. STEP HFpEF included 529 people with symptomatic HFpEF (ejection fraction greater than 45%) and obesity (BMI greater than 30 kg/m2). Dual primary endpoints were change in KCCQ-CSS from baseline to week 52 and change in body weight from baseline to week 52; with key secondary endpoints of change in 6MWD from baseline to week 52, hierarchical composite endpoint (all cause death, heart failure events, difference in KCCQ-CSS change and difference in 6MWD change from baseline to week 52), and change in C-reactive protein from baseline (screening) to week 52.

The ongoing STEP HFpEF-DM trial – another study of HFpEF and obesity in people with type 2 diabetes – is to be included in the regulatory submission. STEP HFpEF-DM is expected to complete in Q4 2023, and subject to positive outcomes Novo Nordisk expects to file for approval of Wegovy label update in the US and EU in the first half of 2024.

See- "Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity"; Mikhail N. Kosiborod, M.D., Steen Z. Abildstrøm, Ph.D., Barry A. Borlaug, M.D., Javed Butler, M.D., Søren Rasmussen, Ph.D., Melanie Davies, M.D., G. Kees Hovingh, M.D., Ph.D., Dalane W. Kitzman, M.D., Marie L. Lindegaard, M.D., D.M.Sc., Daniél V. Møller, M.D., Ph.D., Sanjiv J. Shah, M.D., Marianne B. Treppendahl, M.D., Ph.D., et al., for the STEP-HFpEF Trial Committees and Investigators. August 25, 2023.DOI: 10.1056/NEJMoa2306963.