Tue, 23 Mar 2021 14:17:00 -0400
PLAINSBORO, N.J., March 23, 2021 /PRNewswire/ -- New results from the STEP phase 3a clinical trial program demonstrated weight loss with investigational treatment of once-weekly subcutaneous semaglutide 2.4 mg versus placebo. In the STEP 4 trial, study participants who reached the maintenance dose of semaglutide 2.4 mg during a 20-week run-in period were randomized to either continue treatment with semaglutide 2.4 mg or switch to placebo for 48 weeks.1 The full results of the STEP 4 trial were presented today at the virtual Endocrine Society (ENDO) 2021 Annual Meeting and published in the Journal of the American Medical Association.
"For people with obesity, maintaining weight loss in the long-term is challenging as both physiological and hormonal changes that occur following an initial weight loss can lead to weight regain. These changes, known as metabolic adaptation, result in lasting increased levels of hunger and desire to eat while reducing energy expenditure," said Dr. Domenica Rubino, lead investigator of the STEP 4 trial and Director of Washington Center for Weight Management and Research. "Like any other chronic disease, obesity requires a long-term, individualized approach to care, inclusive of medication and lifestyle components."
Two distinct statistical approaches to evaluating the effects of semaglutide 2.4 mg were used in the STEP 4 trial; a primary statistical approach (treatment policy estimand) that assessed the treatment effect regardless of adherence or use of other anti-obesity therapies, and a secondary statistical approach (trial product estimand) that evaluated the treatment effect if all participants in the trial adhered to the randomized treatment and did not initiate any other treatment methods.2
Following the 20-week run-in period, patients who continued treatment with semaglutide 2.4 mg for an additional 48 weeks continued to lose weight with a statistically significant additional mean weight loss of 7.9% (8.8% for the trial product estimand), while those who were switched to placebo following the 20-week run-in period regained 6.9% of their body weight (6.5% for the trial product estimand) from week 20 to week 68. The estimated treatment difference [ETD] for the treatment policy estimand was -14.8%; 95% confidence interval [CI]: -16.0, -13.5; p<0.0001.1 Observed as a secondary endpoint, people who stayed on semaglutide 2.4 mg throughout the entire 68-week trial achieved a total weight loss of 17.4% (18.2% for the trial product estimand). Both treatment groups followed a reduced-calorie diet and increased physical activity program throughout the study.1
"Obesity is a serious, chronic, and, unfortunately, misunderstood disease that requires long-term care that may include medication," said Anne Phillips, MD, senior vice president, Clinical, Medical and Regulatory Affairs at Novo Nordisk. "These data help show how this new potential therapy could make a difference for people struggling to find options. With semaglutide 2.4 mg, we are hopeful that we can help people living with obesity reach and maintain meaningful weight loss."
The most common adverse events with semaglutide 2.4 mg were nausea, diarrhea and constipation (mostly transient and mild-to-moderate). During the run-in period, 5.3% of participants discontinued treatment due to adverse events. During the randomized period, 2.4% and 2.2% discontinued treatment with semaglutide 2.4 mg and placebo, respectively.1
About STEP 4 and the STEP clinical trial program
STEP 4 was a 68-week phase 3a randomized, double-blind, multicenter, placebo-controlled trial that compared the safety and efficacy of once-weekly subcutaneous semaglutide 2.4 mg versus placebo on change in body weight. The trial was designed to assess the effect of continuing versus discontinuing semaglutide 2.4 mg in adults with obesity (BMI ≥30 kg/m2), or overweight (BMI ≥27 kg/m2) with at least one weight-related comorbidity and without type 2 diabetes (HbA1c <6.5%). During the 20-week run-in period (Week 0 to Week 20), participants were treated with semaglutide (16 weeks dose escalation, followed by 4 weeks at the target dose) as an adjunct to lifestyle intervention (–500 kcal/day diet together with 150 minutes/week of physical activity). Following the run-in period, the 803 people who reached the maintenance dose of semaglutide (2.4 mg) reduced their mean body weight from 107.2 kg (Week 0) to 96.1 kg (Week 20) and were randomized (in a 2:1 ratio) to continue treatment with semaglutide 2.4 mg or switch to placebo for a further 48 weeks (Week 20 to Week 68).1, 2
The primary endpoint of the trial was the percent change in body weight from randomization (Week 20) to the end of treatment (Week 68). Confirmatory secondary endpoints included change in waist circumference, systolic blood pressure, and physical functioning score on the 36-item Short Form Survey (SF-36), assessed from randomization (Week 20) to the end of treatment (Week 68).3 Supportive secondary endpoints included percent change in body weight from baseline (Week 0) to the end of treatment (Week 68).3
STEP (Semaglutide Treatment Effect in People with obesity) is a phase 3 clinical development program with once-weekly subcutaneous semaglutide 2.4 mg in obesity. The global clinical phase 3a program consists of four trials and has enrolled approximately 4,500 adults with overweight or obesity.2
About subcutaneous semaglutide 2.4 mg for weight
Once-weekly semaglutide 2.4 mg is being investigated by Novo Nordisk as a potential treatment option for obesity. Semaglutide is an analogue of the human glucagon-like peptide-1 (GLP-1) hormone.4
Obesity is a chronic, progressive and misunderstood disease that requires long-term medical management.5,6 One key misunderstanding is that this is a disease of willpower, when in fact there is underlying biology that prevents people losing weight and keeping it off.7 Obesity is influenced by a variety of factors, including genetics, appetite signals, behavior and the environment.7 It is a gateway disease and is associated with at least 60 other health conditions.8 The current COVID-19 pandemic has highlighted that obesity also increases the risk for severe illness and hospitalization due to COVID-19.9,10,11,12
The global increase in the prevalence of obesity is a public health issue that has severe cost implications to healthcare systems.13,14 In the United States, more than 42% of adults live with obesity.15
1 Domenica R, Abrahamsson N, et al. Weight loss maintenance with once-weekly semaglutide 2.4 mg in adults with overweight or obesity reaching maintenance dose. Presented at ENDO Annual Meeting. March 20-23, 2021.
2 Kushner RF, Calanna S, Davies M, et al. Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5. Obesity. 2020; 28:1050-1061.
3 ClinicalTrials.gov. Research Study Investigating How Well Semaglutide Works in People Suffering From Overweight or Obesity (STEP 4). ClinicalTrials.gov Identifier: NCT03548987. Available from: https://clinicaltrials.gov/ct2/show/NCT03548987. Last Accessed March 2021.
4 J Lau, P Bloch, L Schaffer, et al. Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide. J Med Chem. 2015; 58:7370-80.
5 American Medical Association. A.M.A Adopts New Policies on Second Day of Voting at Annual Meeting. Obesity as a Disease. Available at: https://news.cision.com/american-medical-association/r/ama-adopts-new-policies-on-second-day-of-voting-at-annual-meeting,c9430649. Last accessed: March 2021.
6 Bray GA, Kim KK, Wilding JPH. World Obesity Federation. Obesity: a chronic relapsing progressive disease process. A position statement of the World Obesity Federation. ObesRev. 2017;18(7):715-723. doi:10.1111/obr.12551.
7 Wright SM, Aronne LJ. Causes of obesity. Abdom Imaging. 2012;37(5):730-732.
8 Bays HE, McCarthy W, Christensen S, et al. Obesity Algorithm, presented by the Obesity Medicine Association. Available at: https://obesitymedicine.org/obesity-algorithm/. Last Accessed: March 2021.
9 Finer N, Garnett SP and Bruun JM. COVID-19 and obesity. Clin Obes. 2020; 10:e12365.
10 Ryan DH, Ravussin E and Heymsfield S. COVID 19 and the Patient with Obesity - The Editors Speak Out. Obesity ( Silver Spring ). 2020; 28:847.
11 Body Mass Index and Risk for COVID-19–Related Hospitalization, Intensive Care Unit Admission, Invasive Mechanical Ventilation, and Death - United States, March–December 2020. Centers for Disease Control and Prevention. https://www.cdc.gov/mmwr/volumes/70/wr/mm7010e4.htm?s_cid=mm7010e4_w. Updated March 8, 2021. Last Accessed: March 2021.
12 Obesity, Race/Ethnicity, and COVID-19. Centers for Disease Control and Prevention. https://www.cdc.gov/obesity/data/obesity-and-covid-19.html. Updated March 9, 2021. Last Accessed: March 2021.
13 World Health Organization. Obesity and Overweight Factsheet no. 311. Available at: http://www.who.int/mediacentre/factsheets/fs311/en/. Last accessed: March 2021.
14 Cawley J, Meyerhoefer C, Biener A, et al. Savings in Medical Expenditures Associated with Reductions in Body Mass Index Among US Adults with Obesity, by Diabetes Status. Pharmacoeconomics. 2015; 33:707–722
15 Adult Obesity Facts. Centers for Disease Control and Prevention. https://www.cdc.gov/obesity/data/adult.html. Updated February 11, 2020. Last Accessed: March 2021.
SOURCE Novo Nordisk